102 results on '"Kukreti, Vishal"'
Search Results
2. Survivorship care for patients curatively treated for Hodgkin's and non-Hodgkin's lymphoma: a scoping review.
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Powis M, Hack S, Fazelzad R, Hodgson D, and Kukreti V
- Abstract
Purpose: We undertook a scoping review of the literature to synthesize what is known about lymphoma survivorship and develop a comprehensive set of lymphoma-specific survivorship recommendations., Methods: We searched the peer-reviewed literature from January 1995 to April 2022, focused on topics relevant to survivorship care in patients ≥ 18 years of age, treated curatively for non-Hodgkin's and Hodgkin's lymphoma, and in remission for at least 2 years., Results: We retained 92 articles; themes included late effects of treatment (53.3%, 49/92), particularly fatigue and sleep disturbances, and fertility, as well as psychosocial considerations of survivors (27.2%; 25/92), screening for secondary malignancies (22.8%; 21/92), outcomes of interventions to improve survivorship care (10.9%; 10/92), and best practices and elements for survivorship plans (8.7%; 8/92). While there were published guidelines for screening for recurrence and secondary malignancies, despite the considerable number of articles on the psychosocial aspects of survivorship care, there remains limited guidance on screening frequency and management strategies for anxiety and depression, sleep disturbances, and treatment-related fatigue within the lymphoma population., Conclusion: We have developed a comprehensive set of lymphoma-survivorship recommendations; however, work is needed to adapt them to local healthcare contexts., Implications for Survivors: While there is a focus in the literature on the long-term psychosocial impacts of cancer and its treatment on lymphoma survivors, there remains no concrete recommendations on effective screening and management of detriments to quality of life such as anxiety, depression, fatigue, and distress, and availability of local resources vary widely., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
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- 2023
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3. The Impact of CD34 + Cell Collection Yields for Autologous Transplant on Survival Outcomes in Multiple Myeloma.
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Lebel E, Lajkosz K, Masih-Khan E, Reece D, Trudel S, Tiedemann R, Prica A, Kukreti V, and Chen C
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- Humans, Transplantation, Autologous, Bortezomib therapeutic use, Hematopoietic Stem Cell Mobilization, Retrospective Studies, Multiple Myeloma therapy, Peripheral Blood Stem Cell Transplantation, Hematopoietic Stem Cell Transplantation
- Abstract
Introduction: According to previous data, higher yields of stem-cells collected to support autologous transplantation may predict for improved outcomes. We aimed to assess the association between high stem-cells collection and survival outcomes in multiple myeloma (MM) MATERIALS AND METHODS: We reviewed all patients who underwent autologous transplantation for MM at our center over a 10-year period, and initially used a predefined threshold of 8 × 10
6 /kg used in previous studies., Results: Six hundred twenty-one patients were analyzed. Higher mobilization did not correlate with favorable outcomes post-transplant. The most efficient mobilizers, collecting ≥8 × 106 /kg (n = 478) achieved a shorter median progression-free survival (PFS) of 24.1m versus 34.5m in patients collecting 4.5 to 8 × 106 /kg (n = 129). A small group (n = 14) collecting ≤4.5 × 106 /kg but minimum of 2 × 106 /kg to support autologous transplantation exhibited the worst outcomes (median PFS 11.4m). Further analysis of potential confounders identified greater use of bortezomib induction in the lower mobilizers, however, sensitivity analysis in patients receiving bortezomib revealed similar results- worst outcomes to the most efficient mobilizers., Conclusion: Although bortezomib is not considered stem-cell toxic, it may be associated with lower stem cell collection yields. Bortezomib's efficacy at induction may partially explain the improved outcomes, however, other factors may be involved, and are discussed. We can conclude that with our large cohort and long follow-up, high stem-cell mobilization does not appear to predict for a long-term survival advantage., Competing Interests: Disclosure The authors had no conflict of interests to disclose., (Copyright © 2023 Elsevier Inc. All rights reserved.)- Published
- 2023
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4. Very late relapse in Hodgkin lymphoma: Characterizing an understudied population.
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Cherniawsky H, Ting E, Zhang JZ, Xu W, Prica A, Bhella S, Yang C, Kridel R, Vijenthira A, Kukreti V, Crump M, and Kuruvilla J
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- Humans, Male, Antineoplastic Combined Chemotherapy Protocols, Neoplasm Recurrence, Local pathology, Canada, Transplantation, Autologous, Hodgkin Disease therapy, Hodgkin Disease drug therapy
- Abstract
Background: Very late relapse (VLR) occurring >5 years after initial diagnosis is an uncommon event in the management of Hodgkin lymphoma (HL). Limited information regarding risk factors and optimal therapy is available., Patients and Methods: We reviewed patients treated for HL at Princess Margaret Cancer Centre, Toronto, Ontario Canada between January 01, 1999 and 31 December 31, 2018., Results: Thirty-two patients experienced VLR. Median time to first relapse was 7.2 years. Most patients were treated with CMT both at initial diagnosis and relapse. Male gender (P = .04) and increased age at initial diagnosis (P = .008; HR 1.09 (95% CI: 1.02-1.15)) were identified as risk factors for inferior survival on univariate analysis. Stage, histology, treatment modality and risk assessment at diagnosis or relapse did not have a significant impact on survival outcomes. ASCT at first relapse had no impact on time to second progression (HR 1.72; 95% CI, 0.35-8.53; P = .51) or overall survival from first relapse (HR 1.55; 95% CI, 0.3-8.03; P = .6)., Conclusion: Our data aligns with the limited information available in VLR HL suggesting the negative impact of age and male gender on this rare event. Additionally, our data did not show benefit of ASCT at first relapse in terms of survival outcomes in this population, though this analysis is limited by small sample size. Further study of optimal therapy to prevent and treat VL in the era of novel agents is critical., Competing Interests: Disclosure The authors declare not conflicts of interest regarding this study., (Copyright © 2023. Published by Elsevier Inc.)
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- 2023
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5. A Web-Based Cancer Self-Management Program (I-Can Manage) Targeting Treatment Toxicities and Health Behaviors: Human-Centered Co-design Approach and Cognitive Think-Aloud Usability Testing.
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Howell D, Bryant Lukosius D, Avery J, Santaguida A, Powis M, Papadakos T, Addario V, Lovas M, Kukreti V, Haase K, Mayo SJ, Papadakos J, Moradian S, and Krzyzanowska MK
- Abstract
Background: Patients with cancer require adequate preparation in self-management of treatment toxicities to reduce morbidity that can be achieved through well-designed digital technologies that are developed in co-design with patients and end users., Objective: We undertook a user-centered co-design process in partnership with patients and other knowledge end users to develop and iteratively test an evidence-based and theoretically informed web-based cancer self-management program (I-Can Manage). The specific study aims addressed in 2 phases were to (1) identify from the perspective of patients with cancer and clinicians the desired content, features, and functionalities for an online self-management education and support (SMES) program to enable patient self-management of treatment toxicities (phase 1); (2) develop the SMES prototype based on human-centered, health literate design principles and co-design processes; and (3) evaluate usability of the I-Can Manage prototype through user-centered testing (phase 2)., Methods: We developed the I-Can Manage program using multiperspective data sources and based on humanistic and co-design principles with end users engaged through 5 phases of development. We recruited adult patients with lung, colorectal, and lymphoma cancer receiving systemic treatments from ambulatory clinics in 2 regional cancer programs for the qualitative inquiry phase. The design of the program was informed by data from qualitative interviews and focus groups, persona and journey mapping, theoretical underpinnings of social cognitive learning theory, and formalized usability testing using a cognitive think-aloud process and user satisfaction survey. A co-design team comprising key stakeholders (human design experts, patients/caregiver, clinicians, knowledge end users, and e-learning and digital design experts) was involved in the developmental process. We used a cognitive think-aloud process to test usability and participants completed the Post-Study System Usability Questionnaire (PSSUQ)., Results: In the initial qualitative inquiry phase, 16 patients participated in interviews and 19 clinicians participated in interviews or focus groups and 12 key stakeholders participated in a persona journey mapping workshop to inform development of the program prototype. The I-Can Manage program integrates evidence-based information and strategies for the self-management of treatment toxicities and health-promoting behaviors in 6 e-learning modules (lay termed "chapters"), starting with an orientation to self-management. Behavioral exercises, patient written and video stories, downloadable learning resources, and online completion of goals and action plans were integrated across chapters. Patient participants (n=5) with different cancers, gender, and age worked through the program in the human factors laboratory using a cognitive think-aloud process and all key stakeholders reviewed each chapter of the program and approved revisions. Results of the PSSUQ (mean total score: 3.75) completed following the cognitive think-aloud process (n=5) suggest patient satisfaction with the usability of I-Can Manage., Conclusions: The I-Can Manage program has the potential for activating patients in self-management of cancer and treatment toxicities but requires testing in a larger randomized controlled trial., (©Doris Howell, Denise Bryant Lukosius, Jonathan Avery, Athina Santaguida, Melanie Powis, Tina Papadakos, Vincenzo Addario, Mike Lovas, Vishal Kukreti, Kristen Haase, Samantha J Mayo, Janet Papadakos, Saeed Moradian, Monika K Krzyzanowska. Originally published in JMIR Cancer (https://cancer.jmir.org), 21.07.2023.)
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- 2023
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6. A Phase II, Open-Label Study of an Accelerated Infusion Rate of Daratumumab in Patients With Relapsed and Refractory Multiple Myeloma.
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Stakiw J, Kodad S, LeBlanc R, Sebag M, Hay AE, Kukreti V, Côté J, Camacho F, Fu M, Gul E, and Reece D
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- Humans, Antibodies, Monoclonal adverse effects, Pandemics, Prospective Studies, Retrospective Studies, COVID-19, Multiple Myeloma drug therapy
- Abstract
Introduction/background: Daratumumab is an anti-CD38 monoclonal antibody initially approved as a single agent for the treatment of relapsed and refractory multiple myeloma. The infusion-related reactions (IRRs) commonly seen with intravenous daratumumab have been managed by prolonging the first infusion, temporarily stopping/slowing the rate if reactions occur and using adequate pre- and post-infusion medications. Several retrospective studies have evaluated shorter infusions after ≥ 2 prior doses administered at the standard rates. Although the shorter infusions were well-tolerated, patients in these reports were given heterogeneous daratumumab regimens and had often already received multiple doses at the longer standard rates., Patients and Methods: CMRG-009 is a prospective study designed to demonstrate the safety of accelerated daratumumab infusions commencing with the second dose. After an initial dose on Cycle 1 Day consisting of 8 mg/kg over 4 hours, all subsequent doses were given over 90 minutes., Results: No grade 3 IRRs were observed with the 90-minutes infusions. Both the safety profile and anti-myeloma effects were otherwise similar to those observed with other single agent daratumumab studies using longer infusion times., Conclusion: This is the first formal prospective trial using infusion times shorter than the standard schedule directly after an initial 4-hours dose. This rapid infusion protocol has resulted in more efficient resource utilization and has become the standard protocol for the use in all intravenous daratumumab regimens in Canada. This approach has been particularly helpful in shortening chair time during the COVID-19 pandemic and providing a useful alternative in jurisdictions without access to subcutaneous daratumumab., Competing Interests: Disclosure Stakiw J: Research Funding: Roche, Janssen; Honoraria: BMS, Novartis, Amgen, Celgene, Janssen, Lundbeck. Kodad S: None. Leblanc R: Research Funding: Celgene; Honoraria: BMS/Celgene, Janssen, Amgen, Novartis, Takeda. Sebag M: Honoraria: Janssen, Amgen, Takeda, Celgene; Research Funding: Janssen. Hay A: Research Funding: Seattle Genetics, Roche, Janssen, Amgen, Novartis, Celgene, AbbVie, Karyopharm. Kukreti V: Honoraria: Celgene, Amgen, Kyowa Kirin. Cote J: Honoraria: Celgene, Takeda, Janssen, Amgen. Camacho F: Paid Consulting: Janssen, AbbVie, Bausch-Health, Otsuka Canada. Fu M: None. Gul E: None. Reece D: Research funding: Celgene, Janssen, Takeda, Merck, BMS, Millennium; Consultancy: Celgene, Janssen, Amgen, Karyopharm, Takeda; Honoraria: Celgene, Janssen, Amgen, Takeda, Sanofi., (Copyright © 2023 Elsevier Inc. All rights reserved.)
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- 2023
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7. Implementation of medication reconciliation in outpatient cancer care.
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Powis M, Dara C, Macedo A, Hack S, Ma L, Mak E, Morley L, Kukreti V, Dave H, Kirkby R, and Krzyzanowska MK
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- Humans, Medication Reconciliation, Outpatients, Pandemics, Electronic Health Records, COVID-19, Neoplasms drug therapy
- Abstract
Background: Medication reconciliation (MedRec) is a process where providers work with patients to document and communicate comprehensive medication information by creating a complete medication list (best possible medication history (BPMH)) then reconciling it against what patient is actually taking to identify potential issues such as drug-drug interactions. We undertook an environmental scan of current MedRec practices in outpatient cancer care to inform a quality improvement project at our centre with the aim of 30% of patients having a BPMH or MedRec within 30 days of initiating treatment with systemic therapy., Methods: We conducted semi-structured interviews with key stakeholders from 21 cancer centres across Canada, probing on current policies, and barriers and facilitators to MedRec. Guided by the findings of the scan, we then undertook a quality improvement project at our cancer centre, comprising six iterative improvement cycles., Results: Most institutions interviewed had a process in place for collecting a BPMH (81%) and targeted patients initiating systemic therapy (59%); however, considerable practice variation was noted and completion of full MedRec was uncommon. Lack of resources, high patient volumes, lack of a common medical record spanning institutions and settings which limits access to medication records from external institutions and community pharmacies were identified as significant barriers. Despite navigating challenges related to the COVID-19 pandemic, we achieved 26.6% of eligible patients with a documented BPMH. However, uptake of full MedRec remained low whereby 4.7% of patients had a documented MedRec., Conclusions: Realising improvements to completion of MedRec in outpatient cancer care is possible but takes considerable time and iteration as the process is complex. Resource allocation and information sharing remain major barriers which need to be addressed in order to observe meaningful improvements in MedRec., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
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- 2023
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8. Impact of a Training Program on Oncology Nurses' Confidence in the Provision of Self-Management Support and 5As Behavioral Counseling Skills.
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Howell D, McGowan P, Bryant-Lukosius D, Kirkby R, Powis M, Sherifali D, Kukreti V, Rask S, and Krzyzanowska MK
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Background: Cancer patients and their families play a central role in the self-management of the medical, emotional, and lifestyle consequences of cancer. Nurses with training in self-management support can enable cancer patients to better manage the effects of cancer and treatment., Methods: As part of a randomized controlled trial, we developed a training program to build nurses' confidence in the provision of self-management support (SMS). The SMS skills taught were adapted from the Stanford Peer Support training programs and embedded within the 5As (Assess, Advise, Agree, Assist, and Arrange) behavioral counseling process. We evaluated the impact of the training program on oncology nurses' and coaches' confidence using a Student's t-test for paired samples in a nonrandomized, one-group pre/postsurvey., Results: Participants were experienced oncology nurses from three participating cancer centers. A two-tailed Student's t-test for paired samples showed a significant improvement in nurses' confidence for the 15 SMS microskills targeted in the training between the pretest and post-test as follows: for Center 1, a mean difference of 0.79 (t = 7.18, p ≤ 0.00001); for Center 2, a mean difference of 0.73 (t = 8.4, p ≤ 0.00001); for Center 3, a mean difference of 1.57 (t = 11.45, p ≤ 0.00001); and for coaches, a mean difference of 0.52 (t = 7.6, p ≤ 0.00001)., Conclusions: Our training program improved oncology staff nurses' and cancer coaches' confidence in 15 SMS microskills and has potential for SMS training of nurses in routine care.
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- 2023
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9. Feasibility and Effectiveness of Self-Management Education and Coaching on Patient Activation for Managing Cancer Treatment Toxicities.
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Howell D, Pond GR, Bryant-Lukosius D, Powis M, McGowan PT, Makuwaza T, Kukreti V, Rask S, Hack S, and Krzyzanowska MK
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- Humans, Middle Aged, Patient Participation, Quality of Life psychology, Feasibility Studies, Ontario, Self-Management, Mentoring, Lung Neoplasms
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Background: Poorly managed cancer treatment toxicities negatively impact quality of life, but little research has examined patient activation in self-management (SM) early in cancer treatment., Methods: We undertook a pilot randomized trial to evaluate the feasibility, acceptability, and preliminary effectiveness of the SMARTCare (Self-Management and Activation to Reduce Treatment Toxicities) intervention. This intervention included an online SM education program (I-Can Manage) plus 5 sessions of telephone cancer coaching in patients initiating systemic therapy for lymphoma or colorectal or lung cancer at 3 centers in Ontario, Canada, relative to a usual care control group. Patient-reported outcomes included patient activation (Patient Activation Measure [PAM]), symptom or emotional distress, self-efficacy, and quality of life. Descriptive statistics and Wilcoxon rank-sum tests were used to examine changes over time (baseline and at 2, 4, and 6 months) within and between groups. We used general estimating equations to compare outcomes between groups over time. The intervention group completed an acceptability survey and qualitative interviews., Results: Of 90 patients approached, 62 (68.9%) were enrolled. Mean age of the sample was 60.5 years. Most patients were married (77.1%), were university educated (71%), had colorectal cancer (41.9%) or lymphoma (42.0%), and had stage III or IV disease (75.8%). Attrition was higher in the intervention group than among control subjects (36.7% vs 25%, respectively). Adherence to I-Can Manage was low; 30% of intervention patients completed all 5 coaching calls, but 87% completed ≥1. Both the continuous PAM total score (P<.001) and categorical PAM levels (3/4 vs 1/2) (P=.002) were significantly improved in the intervention group., Conclusions: SM education and coaching early during cancer treatment may improve patient activation, but a larger trial is needed., Clinicaltrials: gov Identifier: NCT03849950.
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- 2023
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10. Post Salvage Therapy Autologous Transplant for Relapsed Myeloma, Ongoing Relevance within Modern Treatment Paradigms?
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Khan S, Reece D, Atenafu EG, Bhella S, Chen C, Masih-Khan E, Paul H, Prica A, Tiedemann R, Trudel S, and Kukreti V
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- Humans, Autografts, Salvage Therapy, Retrospective Studies, Neoplasm Recurrence, Local drug therapy, Transplantation, Autologous, Antineoplastic Combined Chemotherapy Protocols adverse effects, Multiple Myeloma drug therapy, Hematopoietic Stem Cell Transplantation
- Abstract
Background: Salvage transplant has been historically considered effective therapy for myeloma patients relapsing after first transplant, if they achieved adequate remission duration. However, the efficacy of novel agent combinations has called this paradigm into question., Materials and Methods: We performed a retrospective analysis in a homogeneously treated cohort of 106 patients undergoing ASCT2 at our institution, all of whom received novel agent-based chemotherapy (immunomodulatory agent [IMiD] and/or proteasome inhibitor [PI]) for both induction and relapse. As an exploratory objective we assessed whether predictive thresholds of progression free survival post first transplant (ASCT1) for benefit post ASCT2 vary with use of IMiD maintenance post ASCT1., Results: The overall response rate (ORR) was 98% post-ASCT2 and treatment-related mortality (TRM) was low at 1.8%. With a median follow-up of 26 months (range 0.5-85) from ASCT2, median overall survival (OS) is estimated at 80 months (95% CI: ≥ 49-months) and median progression-free survival after ASCT2 (PFS2) at 24 months (95% CI 19-39). PFS post first transplant (PFS1) at >/= 50 months was associated with improved OS. Predictors of PFS2 included PFS1 ≤42 months and progression on IMiD-based maintenance post- ASCT1., Conclusion: ASCT2 continues to offer acceptable outcomes for most patients treated within modern day treatment paradigms, with longer PFS after ASCT1 and IMiD non-refractory disease being associated with improved outcomes., (Copyright © 2022 Elsevier Inc. All rights reserved.)
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- 2023
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11. Clinical utility of interim CT scans in patients receiving chemoimmuntherapy for first line treatment of follicular lymphoma.
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Manji F, Bhella S, Kridel R, Kukreti V, Kuruvilla J, Prica A, and Crump M
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- Humans, Retrospective Studies, Tomography, X-Ray Computed, Remission Induction, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Lymphoma, Follicular
- Abstract
Interim imaging with computed tomography (iCT) to assess response is common during frontline chemoimmunotherapy for follicular lymphoma (FL), but there is little evidence of its utility. We retrospectively reviewed outcomes of iCT in 190 patients with biopsy-proven FL who received first-line chemoimmunotherapy from 2003-2018. Most iCTs showed partial response (PR, 83%), with a minority showing complete response (CR, 8%) or stable disease (5%). Seven patients (4%) had radiographic disease progression (PD) on iCT; on repeat biopsy, four had another malignancy identified and three had transformation to DLBCL. Only one had asymptomatic PD. The 3-year PFS of all patients was 74% (median follow up 75 months). Patients with PR on iCT had similar 3-year PFS and OS as those with CR. In conclusion, iCT has limited utility in identifying patients with asymptomatic early progression during first-line treatment. Patients with PD mid-treatment warrant biopsy to identify histologic transformation or other malignancies.
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- 2022
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12. Clinical significance of clonal hematopoiesis in the setting of autologous stem cell transplantation for lymphoma.
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Lackraj T, Ben Barouch S, Medeiros JJF, Pedersen S, Danesh A, Bakhtiari M, Hong M, Tong K, Joynt J, Arruda A, Minden MD, Kuruvilla J, Bhella S, Kukreti V, Crump M, Prica A, Chen C, Deng Y, Xu W, Pugh TJ, Keating A, Dick JE, Abelson S, and Kridel R
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- Humans, Transplantation, Autologous adverse effects, Clonal Hematopoiesis, Stem Cell Transplantation adverse effects, Retrospective Studies, Hematopoietic Stem Cell Transplantation adverse effects, Lymphoma therapy, Lymphoma complications, Hodgkin Disease complications, Neoplasms, Second Primary therapy, Neoplasms, Second Primary genetics
- Abstract
Autologous stem cell transplantation (ASCT) remains a key therapeutic strategy for treating patients with relapsed or refractory non-Hodgkin and Hodgkin lymphoma. Clonal hematopoiesis (CH) has been proposed as a major contributor not only to the development of therapy-related myeloid neoplasms but also to inferior overall survival (OS) in patients who had undergone ASCT. Herein, we aimed to investigate the prognostic implications of CH after ASCT in a cohort of 420 lymphoma patients using ultra-deep, highly sensitive error-correction sequencing. CH was identified in the stem cell product samples of 181 patients (43.1%) and was most common in those with T-cell lymphoma (72.2%). The presence of CH was associated with a longer time to neutrophil and platelet recovery. Moreover, patients with evidence of CH had inferior 5-year OS from the time of first relapse (39.4% vs. 45.8%, p = .043) and from the time of ASCT (51.8% vs. 59.3%, p = .018). The adverse prognostic impact of CH was not due to therapy-related myeloid neoplasms, the incidence of which was low in our cohort (10-year cumulative incidence of 3.3% vs. 3.0% in those with and without CH, p = .445). In terms of specific-gene mutations, adverse OS was mostly associated with PPM1D mutations (hazard ratio (HR) 1.74, 95% confidence interval (CI) 1.13-2.67, p = .011). In summary, we found that CH is associated with an increased risk of non-lymphoma-related death after ASCT, which suggests that lymphoma survivors with CH may need intensified surveillance strategies to prevent and treat late complications., (© 2022 Wiley Periodicals LLC.)
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- 2022
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13. Implementation and Impact of Choosing Wisely Recommendations in Oncology.
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Nagarajah S, Powis ML, Fazelzad R, Krzyzanowska MK, and Kukreti V
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- Humans, Male, Medical Oncology, Pandemics, Breast Neoplasms, COVID-19 epidemiology, Prostatic Neoplasms therapy
- Abstract
The Choosing Wisely (CW) campaign, launched in 2012, includes oncology-specific recommendations to promote evidence-based care and deimplementation of low-value practices. However, it is unclear to what extent the campaign has prompted practice change. We systematically reviewed the literature to evaluate the uptake of cancer-specific CW recommendations focusing on the period before the declaration of the COVID-19 pandemic. We used Grimshaw's deimplementation framework to thematically group the findings and extracted information on implementation strategies, barriers, and facilitators from articles reporting on active implementation. In the 98 articles addressing 32 unique recommendations, most reported on passive changes in adherence pre-post publication of CW recommendations. Use of active surveillance for low-risk prostate cancer and reduction in staging imaging for early breast cancer were the most commonly evaluated recommendations. Most articles assessing passive changes in adherence pre-post CW publication reported improvement. All articles evaluating active implementation (10 of 98) reported improved compliance (range: 3%-73% improvement). Most common implementation strategies included provider education and/or stakeholder engagement. Preconceived views and reluctance to adopt new practices were common barriers; common facilitators included the use of technology and provider education to increase provider buy-in. Given the limited uptake of oncology-specific CW recommendations thus far, more attention toward supporting active implementation is needed. Effective adoption of CW likely requires a multipronged approach that includes building stakeholder buy-in through engagement and education, using technology-enabled forced functions to facilitate change along with policy and reimbursement models that disincentivize low-value care. Professional societies have a role to play in supporting this next phase of CW., Competing Interests: Monika K. KrzyzanowskaThis author is an Editor for JCO Oncology Practice. Journal policy recused the author from having any role in the peer review of this manuscript.Consulting or Advisory Role: Eisai, Lilly, IpsenResearch Funding: Eisai (Inst), Exelixis (Inst), Lilly (Inst) Vishal KukretiHonoraria: Celgene, Takeda, Amgen, Kirin Kyoto, Eusa PharmaceuticalConsulting or Advisory Role: AmgenNo other potential conflicts of interest were reported.
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- 2022
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14. Predicting the Risks of Aggressive-Intent Chemotherapy Toxicity in Older Patients With Lymphoma: A Prospective Observational Pilot Study.
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Dhir V, Maganti M, Rozenberg D, Kukreti V, Kuruvilla J, Crump M, and Prica A
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- Aged, Aged, 80 and over, Cohort Studies, Geriatric Assessment methods, Humans, Pilot Projects, Prospective Studies, Frailty, Lymphoma diagnosis, Lymphoma drug therapy
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Introduction: Lymphoma is a disease of older patients and while treatment is subtype specific, curative or aggressive intent combination chemotherapy is often recommended. However, there has been limited evidence on which to base treatment decisions for older adults. Our objectives were to assess the utility of risk stratification measures and serial functional tests in predicting chemotherapy toxicity and as well the feasibility of conducting these in older adults undergoing chemotherapy for lymphoproliferative disorders., Materials and Methods: This prospective cohort study recruited lymphoma patients 70 years or older planned for systemic chemotherapy. The Cancer and Aging Research Group (CARG) risk stratification tool and Chemotherapy Risk Assessment Scale for High-Age Patients (CRASH) were calculated at baseline. The Clinical Frailty Scale (CFS), Charlson Comorbidity Index score, grip strength and gait speed test, and toxicity events, were assessed at baseline and serially throughout treatment. Sarcopenia was calculated on CT scans at baseline, midway through treatment, and 1-month after completion of therapy. The primary endpoint was to assess the feasibility of applying these measures in busy ambulatory clinics. These measures were also correlated with clinical outcomes including ≥grade 3 adverse events (AEs), hospitalizations and emergency department visits, dose changes or delays, and overall survival., Results: In total, 30 patients were enrolled (mean age 78.1 ± 6.4 years), of whom 20 were treated with curative intent. A total of 16 patients (53%) experienced grade ≥3 AEs, 9 (56%) of which led to a chemotherapy delay. On univariable analyses, CFS score, a high CARG score, medium to high CRASH score, and the gait speed were associated with grade ≥3 AEs, while only CFS remained significant on multivariable analysis. On univariable analysis, patients with a medium to high risk CRASH score were more likely than low risk patients to have an unplanned emergency department visit or hospitalization., Conclusions: The CFS seems to predict toxicity in this cohort study, with gait speed, CARG and CRASH scores being potentially additional predictive methods of evaluation., (Copyright © 2022 Elsevier Ltd. All rights reserved.)
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- 2022
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15. Risk stratification for relapsed/refractory classical Hodgkin lymphoma integrating pretransplant Deauville score and residual metabolic tumor volume.
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Yhim HY, Eshet Y, Metser U, Lajkosz K, Cooper M, Prica A, Kukreti V, Bhella S, Lang N, Xu W, Rodin D, Hodgson D, Tsang R, Crump M, Kuruvilla J, and Kridel R
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- Antineoplastic Combined Chemotherapy Protocols, Humans, Neoplasm Recurrence, Local, Retrospective Studies, Risk Assessment, Transplantation, Autologous, Tumor Burden, Hematopoietic Stem Cell Transplantation methods, Hodgkin Disease pathology
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Pretransplant Deauville score (DS) is an imaging biomarker used for risk stratification in relapsed/refractory classical Hodgkin lymphoma (cHL). However, the prognostic value of residual metabolic tumor volume (rMTV) in patients with DS 4-5 has been less well characterized. We retrospectively assessed 106 patients with relapsed/refractory cHL who underwent autologous stem cell transplantation. Pretransplant DS was determined as 1-3 (59%) and 4-5 (41%), with a markedly inferior event-free survival (EFS) in patients with DS 4-5 (hazard ratio [HR], 3.14; p = .002). High rMTV
41% (rMTVhigh , ≥4.4 cm3 ) predicted significantly poorer EFS in patients with DS 4-5 (HR, 3.70; p = .014). In a multivariable analysis, we identified two independent factors predicting treatment failure: pretransplant DS combined with rMTV41% and disease status (primary refractory vs. relapsed). These two factors allow to stratify patients into three groups with divergent 2-year EFS: 89% for low-risk (51%; relapsed disease and either pretransplant DS 1-3 or DS 4-5/rMTVlow ; HR 1), 65% for intermediate-risk (28%; refractory disease and either DS 1-3 or DS 4-5/rMTVlow ; HR 3.26), and 45% for high-risk (21%; DS 4-5/rMTVhigh irrespective of disease status; HR 7.61) groups. Pretransplant DS/rMTV41% combination and disease status predict the risk of post-transplant treatment failure and will guide risk-stratified approaches in relapsed/refractory cHL., (© 2022 Wiley Periodicals LLC.)- Published
- 2022
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16. Fixed duration vs. prolonged duration treatment after first line therapy in patients with systemic light chain amyloidosis.
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Rivera Duarte A, Reece D, Li X, Xu W, Paul H, Masih-Khan E, Winter A, Tiedemann R, Prica A, Chen C, Trudel S, and Kukreti V
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- Humans, Middle Aged, Retrospective Studies, Survival Analysis, Treatment Outcome, Amyloidosis drug therapy, Immunoglobulin Light-chain Amyloidosis drug therapy, Multiple Myeloma
- Abstract
Background: The main objective of treatment in systemic light chain amyloidosis (AL amyloidosis) is to achieve the best hematological response. Deeper responses are associated with better organ responses and survival. In this study, we analysed the efficacy of prolonged duration treatment after first line in patients with AL amyloidosis., Methods: Retrospective analysis that included patients older than 18 years with AL amyloidosis. We excluded patients with more than 30% marrow plasmacytosis or concurrent multiple myeloma. Two cohorts identified accordingly if they received or not prolonged treatment after the first line. Survival analysis regarding progression free survival (PFS) and overall survival (OS) estimated with Kaplan-Meier and comparisons between groups with log-rank., Results: Thirty-eight patients were included in the analysis with a median age of 55 years. Twenty-one patients received prolonged duration treatment and 17 did not. In the prolonged duration group, after a median duration of 12 months, the median PFS was 58.8 months. In the fixed duration treatment group, PFS was 30.6 months. The difference was significant with p = .0045 favouring prolonged duration treatment. Organ response was sustained for a longer period in the prolonged duration treatment group. For OS, the difference was not significant., Conclusions: Prolonged duration treatment in patients with systemic light chain amyloidosis correlated with better PFS and deeper organ responses. Prospective studies are needed to analyse this further.
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- 2022
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17. Kinetics of response to first- and second-line therapies in multiple myeloma: Assessment by both M-spikes and light chains.
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Lebel E, Li X, Paul H, Masih-Khan E, Bhella S, Chen C, Prica A, Reece D, Tiedemann R, Trudel S, and Kukreti V
- Subjects
- Antineoplastic Combined Chemotherapy Protocols adverse effects, Bortezomib therapeutic use, Dexamethasone, Humans, Kinetics, Treatment Outcome, Hematopoietic Stem Cell Transplantation, Multiple Myeloma diagnosis, Multiple Myeloma drug therapy
- Abstract
Objectives: The prognostic value of kinetics of response to multiple myeloma (MM) therapy is controversial. We aimed to expand the knowledge on this topic by reviewing the kinetics of response to both first- and second-line MM therapy, utilizing a homogeneously treated cohort and analyzing separately both M-spike and light chain (LC) responses for each patient., Methods: We reviewed all patients who received first-line cyclophosphamide, bortezomib and dexamethasone induction followed by autologous transplant with melphalan and lenalidomide maintenance in our center between 2007 and 2019., Results: Analyzing 360 patients, we observed no correlation between response kinetics to first- versus second-line therapy at the individual patient level. Time to best response to first-line therapy was not a predictor of outcome; however, longer time to best response was highly predictive of a favorable outcome in the second-line setting, independent of other factors. Patients with IgA-MM cleared their M-spike faster than IgG-MM, probably reflecting different half-lives of these isotypes rather than disease biology, as the clearance of LC in both subtypes was similar., Conclusions: Analyzing both M-spike and LC responses in a homogenously treated cohort, we identified important insights regarding the prognostic value of kinetic patterns. Prospective analysis may shed more light on unsolved questions., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
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- 2022
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18. Light Chain Amyloidosis (AL) Associated With B Cell Lymphoma a Single Center Experience.
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la Torre A, Reece D, Crump M, Atenafu EG, Chen C, Prica A, and Kukreti V
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- Humans, Male, Retrospective Studies, Amyloidosis diagnosis, Immunoglobulin Light-chain Amyloidosis complications, Immunoglobulin Light-chain Amyloidosis diagnosis, Lymphoma, B-Cell pathology, Waldenstrom Macroglobulinemia complications, Waldenstrom Macroglobulinemia diagnosis, Waldenstrom Macroglobulinemia drug therapy
- Abstract
Introduction: Light chain (AL) amyloidosis and B-cell lymphoma represent 5% to 7% of all AL, Systemic amyloidosis, deposits in sites remote from the underlying lymphoma, and peritumoral amyloidosis deposition is within the immediate vicinity., Materials and Methods: We conducted a retrospectively study to identify and describe AL with B cell lymphoma at Princess Margaret Cancer Center from 01 January 1997 to 31 July 2019., Results: Thirty-five patients with AL and lymphoma, an incidence of 6, 2%, median age of diagnosis of 66 (range 47 to 86), majority male, most had underlying Waldestrom's Macroglobulinemia. 21 patients with peritumoral AL (PAL), and 15 with systemic AL. 42.8% of the patients had major organ involvement. 35% got treatment with Rituximab with alkylator, 20% received proteasome inhibitors, 17% patients were on a watch and wait approach, amyloid response showed very good partial response > 45.8%, and lymphoma ORR was 42.8%, with a median follow up of 31.5 months. A 36 month overall survival (OS) and progression-free survival (PFS) showed worse outcomes for heart involvement OS (P = .002), PFS (0.057) and IgM subtype OS (P = .02), PFS (0.01)., Conclusion: We have shown adverse outcome with IgM AL and to document a differences in OS and PFS not previously reported for PAL., (Copyright © 2021. Published by Elsevier Inc.)
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- 2021
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19. A descriptive cost-analysis of MYX.1/MCRN003, a phase 2 clinical trial evaluating high-dose weekly carfilzomib, cyclophosphamide, and dexamethasone in relapsed and refractory multiple myeloma.
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Monteith BE, Venner CP, Cheung MC, Pater J, Shepherd L, Richardson H, Reece D, Gul E, Lalancette M, Castonguay V, Kukreti V, Tiedemann R, Phua C, Bhella S, Dudebout J, Sherry M, Yen H, Chen BE, and Hay AE
- Subjects
- Adult, Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Canada, Cyclophosphamide therapeutic use, Dexamethasone therapeutic use, Drug Administration Schedule, Drug Resistance, Neoplasm, Female, Hospitalization economics, Hospitalization statistics & numerical data, Humans, Male, Middle Aged, Multiple Myeloma drug therapy, Multiple Myeloma mortality, Multiple Myeloma pathology, Oligopeptides therapeutic use, Patient Acceptance of Health Care statistics & numerical data, Recurrence, Survival Analysis, Treatment Outcome, Antineoplastic Combined Chemotherapy Protocols economics, Cost of Illness, Costs and Cost Analysis, Cyclophosphamide economics, Dexamethasone economics, Multiple Myeloma economics, Oligopeptides economics
- Abstract
Background: The prevalence of multiple myeloma is increasing and there is a need to evaluate escalating therapy costs (Canadian Cancer Statistics A, 2020). The MYX.1 phase II trial showed that high-dose weekly carfilzomib, cyclophosphamide, and dexamethasone (wKCD) is efficacious in relapsed and refractory disease. We conducted a descriptive cost analysis, from the perspective of the Canadian public healthcare system, using trial data., Methods: The primary outcome was the mean total cost per patient. Resource utilization data were collected from all 75 trial patients over a trial time horizon. Costs are presented in Canadian dollars (2020)., Results: The cost of treatment was calculated from the time of patient (pt) enrollment until the second data lock. The mean total cost was $203 336.08/pt (range $17 891.27-$505 583.55) Canadian dollars (CAD, where 1 CAD = 0.67 Euro (EUR)) and $14 081.45/pt per cycle. The median number of cycles was 15. The predominant cost driver was the cost of chemotherapy accounting for an average of $179 332.78/pt or $12 419.17/pt per cycle. Carfilzomib acquisition accounted for the majority of chemotherapy costs - $162 471.65/pt or $11 251.50/pt per cycle. Fifty-six percent (56%) of patients had at least one hospitalization during the trial period with an average cost of $12 657.86 per hospitalization. Three patients developed thrombotic microangiopathy (TMA) with an average cost of $18 863.32/pt including the cost of hospitalizations and therapeutic plasma exchange., Conclusions: High-dose wKCD is an active triplet regimen for relapsed and refractory multiple myeloma (RRMM) associated with reduced total cost compared with twice-weekly carfilzomib-based regimens., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
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- 2021
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20. The survival impact of maintenance lenalidomide: an analysis of real-world data from the Canadian Myeloma Research Group national database.
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Cherniawsky HM, Kukreti V, Reece D, Masih-Khan E, McCurdy A, Jimenez-Zepeda VH, Sebag M, Song K, White D, Stakiw J, LeBlanc R, Reiman A, Aslam M, Louzada M, Kotb R, Gul E, Atenafu E, and Venner CP
- Subjects
- Antineoplastic Combined Chemotherapy Protocols, Bortezomib therapeutic use, Canada, Dexamethasone therapeutic use, Disease-Free Survival, Humans, Lenalidomide therapeutic use, Maintenance Chemotherapy, Multiple Myeloma drug therapy, Multiple Myeloma epidemiology
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- 2021
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21. The impact of lenalidomide maintenance on second-line chemotherapy in transplant eligible patients with multiple myeloma.
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Cherniawsky HM, Kukreti V, Reece D, Masih-Khan E, McCurdy A, Jimenez-Zepeda VH, Sebag M, Song K, White D, Stakiw J, LeBlanc R, Reiman A, Louzada M, Aslam M, Kotb R, Gul E, Atenafu E, and Venner CP
- Subjects
- Canada, Disease Management, Hematopoietic Stem Cell Transplantation, Humans, Lenalidomide administration & dosage, Maintenance Chemotherapy, Multiple Myeloma diagnosis, Multiple Myeloma mortality, Prognosis, Retrospective Studies, Treatment Outcome, Lenalidomide therapeutic use, Multiple Myeloma therapy, Preoperative Care
- Abstract
Objectives: To understand the impact of therapy sequencing on progression-free (PFS) and overall survival (OS) for the treatment of multiple myeloma (MM). The use of daily, low-dose, lenalidomide maintenance (LM) has raised concern for fostering resistance, preventing its use in the relapsed setting., Methods: We conducted a retrospective analysis of survival outcomes from the Canadian Myeloma Research Group Database. Patients were grouped based on receipt of LM after autologous stem cell transplant and receipt of lenalidomide in second-line therapy, 575 patients were included., Results: Patients treated with LM had statistically similar 2nd PFS when re-exposed to lenalidomide in second-line therapy compared to those receiving non-lenalidomide-containing regimens (10.2 vs 14.0 months, P =.53). This cohort also had the longest 2nd OS, 18 months longer than patients treated with LM who did not receive lenalidomide at relapse (55.3 vs 37 months, P =.004). Patients treated with LM also demonstrated deeper responses to second-line therapy than their non-LM counterparts., Conclusion: Our data suggest that patients progressing on LM who receive lenalidomide-containing therapy at first relapse have comparable 2nd PFS and better 2nd OS compared to non-lenalidomide-containing second-line regimens. Identification of patients mostly likely to benefit from further lenalidomide-containing therapy is paramount., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
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- 2021
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22. Evolving Best Practice for Take-Home Cancer Drugs.
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Pardhan A, Vu K, Gallo-Hershberg D, Forbes L, Gavura S, and Kukreti V
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- Consensus, Humans, Medical Oncology, Ontario, Antineoplastic Agents, Neoplasms drug therapy
- Abstract
Purpose: Take-home cancer drugs (THCDs) have become a standard treatment of many cancers. Robust guidelines have been developed for intravenous chemotherapy drugs, but few exist for THCDs with a focus on decentralized models. Hence, Ontario Health (Cancer Care Ontario) established the Oncology Pharmacy Task Force (OPTF) to develop consensus-based recommendations on best practices for THCDs to ensure that patients receive safe, consistent, high-quality care in the community once they leave the cancer center/practice with a prescription., Methods: The OPTF included 34 members with comprehensive representation. Guidance from leading authorities was extracted through literature review, thematically analyzed, and synthesized to develop 29 recommendations. The consensus process (> 70% agreement) included a three-step modified Delphi method followed by an extensive review process., Results: Sixteen recommendations were developed: training and education for providers (2), drug access (1), prescribing (4), patient and family/caregiver education (3), communication (1), dispensing (3), monitoring for patient adherence and adverse effects (1), and incident reporting (1)., Conclusion: Through a rigorous methodology, the OPTF derived a robust set of recommendations similar to the ASCO/Oncology Nursing Society and ASCO/National Community Oncology Dispensing Association guidelines, further validating and strengthening the applicability across multiple jurisdictions, including those with decentralized models. Unique aspects in a decentralized model include the need for two pharmacy professionals, with one doing cognitive verification of the script and the other dispensing the medication; moreover, they optimize interprofessional communication between community providers and the cancer center/practice health care team., Competing Interests: Kathy VuStock and Other Ownership Interests: Incyte Vishal KukretiHonoraria: Amgen, Takeda Pharmaceuticals, CelgeneNo other potential conflicts of interest were reported.
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- 2021
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23. Syngeneic transplants for multiple myeloma - a single center experience and review of the literature.
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Lebel E, Prica A, Bhella S, Kukreti V, Tiedemann R, Trudel S, Reece D, and Chen C
- Subjects
- Humans, Isografts, Transplantation, Autologous, Transplantation, Isogeneic, Multiple Myeloma diagnosis, Multiple Myeloma therapy
- Published
- 2020
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24. A risk model for relapsed/refractory aggressive NHL integrating clinical risk factors and pretransplant Deauville score.
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Yhim HY, Eshet Y, Metser U, Lim CH, Lajkosz K, Isaev K, Cooper M, Prica A, Kukreti V, Bhella S, Lang N, Lee KH, Xu W, Hodgson D, Tsang R, Yoon SE, Kim SJ, Kim WS, Crump M, Kuruvilla J, and Kridel R
- Subjects
- Antineoplastic Combined Chemotherapy Protocols therapeutic use, Humans, Retrospective Studies, Risk Factors, Transplantation, Autologous, Hematopoietic Stem Cell Transplantation, Lymphoma, Non-Hodgkin drug therapy, Lymphoma, Non-Hodgkin therapy
- Abstract
There are limited data regarding the combined value of the pretransplant Deauville score (DS) from a positron emission tomography scan and clinical risk factors in patients with relapsed/refractory aggressive non-Hodgkin lymphoma (NHL). We performed a retrospective analysis to assess the prognostic role of pretransplant DS in patients with relapsed/refractory aggressive NHL who underwent salvage chemotherapy and autologous stem cell transplantation (ASCT). We identified 174 eligible patients between January 2013 and March 2019. In multivariable analysis, pretransplant DS, B symptoms, and secondary International Prognostic Index (sIPI) were independent risk factors for event-free survival (EFS). These variables were used to derive an integrated risk score that categorized 166 patients with available information for all risk factors into 3 groups: low (n = 92; 55.4%), intermediate (n = 48; 28.9%), and high (n = 26; 15.7%). The new prognostic index showed a strong association with EFS (low-risk vs intermediate-risk hazard ratio [HR], 3.94; 95% confidence interval [CI], 2.16-7.17; P < .001; low-risk vs high-risk HR, 10.83; 95% CI, 5.81-20.19; P < .001) and outperformed models based on clinical risk factors or DS alone. These results were validated in 60 patients from an independent external cohort (low-risk vs intermediate-risk HR, 4.04; 95% CI, 1.51-10.82; P = .005; low-risk vs high-risk HR, 10.49; 95% CI, 4.11-26.73; P < .001). We propose and validate a new prognostic index that risk-stratifies patients undergoing salvage chemotherapy followed by ASCT, thereby identifying patients at high risk for posttransplant treatment failure., (© 2020 by The American Society of Hematology.)
- Published
- 2020
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25. Five biopsies, one diagnosis: challenges in idiopathic multicentric Castleman disease.
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Semenchuk J, Merchant A, Sakhdari A, and Kukreti V
- Subjects
- Adult, Diagnosis, Differential, Humans, Male, Neck, Biopsy methods, Bone Marrow Cells pathology, Castleman Disease diagnosis, Kidney pathology, Liver pathology, Lymph Nodes pathology
- Abstract
A previously healthy 29-year-old man initially presented to the hospital with pleuritic chest pain and shortness of breath. Over the next 2 months he developed ongoing fevers and night sweats with recurrent exudative pleural effusions and ascites. He had an extensive infectious and autoimmune workup that was unremarkable. He had an initial lymph node biopsy that showed reactive changes only. He had an acute kidney injury and his renal biopsy revealed thrombotic microangiopathy. His liver biopsy showed non-specific inflammatory changes. His bone marrow biopsy showed megakaryocyte hyperplasia and fibrosis, which raised suspicion for the thrombocytopenia, ascites, reticulin fibrosis, renal dysfunction and organomegaly syndrome subtype of multicentric Castleman disease. This prompted a repeat lymph node biopsy, showing changes consistent with mixed type Castleman disease that fit with his clinical picture. He was initiated on steroids and siltuximab with significant clinical improvement., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.)
- Published
- 2020
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26. A Case of Rapid Deterioration with Marked Hypergammaglobulinemia.
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Leung F, Lee S, Kukreti V, and Kulasingam V
- Subjects
- Adult, Diagnosis, Differential, Humans, Male, Castleman Disease diagnosis, Clinical Deterioration, Hypergammaglobulinemia, Immunoglobulin G4-Related Disease diagnosis
- Published
- 2020
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27. Validation of the RHL30 digital gene expression assay as a prognostic biomarker for relapsed Hodgkin lymphoma.
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Calvente L, Tremblay-LeMay R, Xu W, Chan FC, Hong M, Zhang T, Yhim HY, Kuruvilla J, Crump M, Kukreti V, Prica A, Regier D, Marra MA, Karsan A, Steidl C, Scott DW, Sabatini P, and Kridel R
- Subjects
- Adult, Autografts, Female, Humans, Male, Middle Aged, Risk Factors, Biomarkers, Tumor biosynthesis, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Hematopoietic Stem Cell Transplantation, Hodgkin Disease metabolism, Hodgkin Disease mortality, Hodgkin Disease therapy
- Abstract
Despite continuing improvements in the management of classical Hodgkin lymphoma (cHL), relapse remains associated with a risk of lymphoma-related mortality. The biological composition of relapse tumour biopsies shows interpatient variability, which can be leveraged to design prognostic biomarkers. Here, we validated the RHL30 assay, a previously reported gene expression model in an independent cohort of 41 patients with relapsed cHL. Patients classified as high-risk by the RHL30 assay had inferior failure-free survival (FFS) after autologous stem cell transplantation (2-year FFS 41% vs. 92%, P = 0·035). The RHL30 model is a robust biomarker that risk-stratifies patients considered for autologous stem cell transplantation., (© 2020 British Society for Haematology and John Wiley & Sons Ltd.)
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- 2020
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28. An open-label, pharmacokinetic study of lenalidomide and dexamethasone therapy in previously untreated multiple myeloma (MM) patients with various degrees of renal impairment - validation of official dosing guidelines.
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Chen CI, Cao Y, Trudel S, Reece DE, Kukreti V, Tiedemann R, Prica A, Paul H, Le LW, Levina O, Kakar S, Lau A, Chen H, and Chen E
- Subjects
- Antineoplastic Combined Chemotherapy Protocols adverse effects, Dexamethasone therapeutic use, Humans, Lenalidomide therapeutic use, Thalidomide therapeutic use, Treatment Outcome, Multiple Myeloma complications, Multiple Myeloma drug therapy, Renal Insufficiency complications
- Abstract
Lenalidomide is a backbone agent in the treatment of multiple myeloma, but dose adjustment is required for those with renal impairment (RI). We evaluated the pharmacokinetics (PK) and safety of lenalidomide and dexamethasone as frontline pre-transplant induction, with doses adjusted at start of each cycle based on creatinine clearance, as per the official dosing guidelines. After 4 cycles, PK studies showed that patients with moderate RI (30 ≤ CrCl < 60 mL/min) receiving 10 mg dosing may be under-dosed and those with severe RI (CrCl <30ml/min) appeared appropriately dosed initially, but sustained significant decreases in maximum serum concentration (Cmax) after repeated dosing, due to rapid clinical improvement and enhanced drug clearance. PK drug monitoring during cycle 1 may facilitate appropriate and timely dose adjustments. Adverse events rates did not vary based on severity of RI. No patient discontinued lenalidomide for toxicity. This supports the feasibility and safety of frontline lenalidomide in transplant-eligible patients with RI.
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- 2020
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29. Feasibility randomised controlled trial of remote symptom chemotherapy toxicity monitoring using the Canadian adapted Advanced Symptom Management System (ASyMS-Can): a study protocol.
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Moradian S, Krzyzanowska M, Maguire R, Kukreti V, Amir E, Morita PP, Liu G, and Howell D
- Subjects
- Feasibility Studies, Humans, Ontario, Prospective Studies, Randomized Controlled Trials as Topic, Research Design, Telephone, Antineoplastic Agents toxicity, Drug Monitoring methods, Neoplasms drug therapy, Symptom Assessment
- Abstract
Introduction: Technology is emerging as a solution to develop home-based, proactive 'real-time' symptom monitoring and management in cancer care. The Advanced Symptom Monitoring and Management System-Canada (ASyMS-Can) is a remote phone-based symptom management system that enables real-time remote monitoring of systemic chemotherapy toxicities., Methods and Analysis: This study is an open-label, prospective, mixed-method, Phase II, 2-arm parallel group assignment (ASyMS-Can vs usual care) feasibility study in patients with cancer receiving systemic (neo-adjuvant or adjuvant) chemotherapy at Princess Margaret Cancer Centre. A total of 114 patients will be recruited in oncology clinics prior to initiation of chemotherapy. Patients in both arms will complete a demographic and a set of questionnaires at enrolment, mid and end of treatment. Patients in intervention arm will be provided with an encrypted, secure, preprogrammed ASyMS phone for symptom reporting daily for the first 14 days of each chemotherapy treatment cycle up to sixth cycle (16 weeks). Feasibility metrics (recruitment, retention and protocol adherence) and outcomes to assess impact of ASyMS-Can include symptom severity, emotional distress, quality of life and acceptability to patients and clinicians., Ethics and Dissemination: The study has received ethical and institutional approvals from the University Health Network. Dissemination will include presentations at national/international conferences, and publications in peer-reviewed journals., Trial Registration Number: NCT03335189., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
- Published
- 2020
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30. Toxicity and survival outcomes of autologous stem cell transplant in multiple myeloma patients with renal insufficiency: an institutional comparison between two eras.
- Author
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Li AY, Atenafu EG, Bernard RS, Masih-Khan E, Reece D, Franke N, Tiedemann R, Prica A, Trudel S, Kukreti V, and Chen CI
- Subjects
- Disease-Free Survival, Humans, Melphalan, Retrospective Studies, Stem Cell Transplantation, Transplantation, Autologous, Treatment Outcome, Hematopoietic Stem Cell Transplantation, Multiple Myeloma therapy, Renal Insufficiency therapy
- Abstract
Autologous stem cell transplant (ASCT) is a feasible treatment option for multiple myeloma (MM) patients with renal insufficiency; however, these patients tend to experience higher rates of drug toxicity and transplant-related mortality (TRM) during ASCT. Recent adoption of bortezomib-based induction regimens and dose reduction of melphalan during conditioning may improve outcomes in this population. In this single center retrospective study, we compared the toxicity and survival outcomes of 96 MM patients with renal insufficiency undergoing ASCT between two eras: 1998-2007 and 2008-2016. The proportion of dialysis dependent patients was similar in both groups (49 and 45%). We found no TRM in those transplanted more recently as compared with 13% in the older era of ASCT. There were significantly more high grade (grades 3-4) toxicities in the older era of ASCT including high grade electrolyte abnormalities, mucositis, delirium, and bleeding. Patients transplanted more recently had significantly higher overall response rate (ORR) as well as deeper responses to ASCT (≥VGPR in 79% vs 39%). Progression-free survival (PFS) was prolonged by 26 months in the more recent era compared with the older era. Overall, improvements in treatment regimens have resulted in reduced TRM and toxicities for patients with renal insufficiency undergoing ASCT.
- Published
- 2020
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31. Evaluation of Lymphadenopathy and Suspected Lymphoma in a Lymphoma Rapid Diagnosis Clinic.
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Nixon S, Bezverbnaya K, Maganti M, Gullane P, Reedijk M, Kuruvilla J, Prica A, Kridel R, Kukreti V, Bennett S, Rogalla P, Delabie J, Pintilie M, and Crump M
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Diagnosis, Differential, Female, Humans, Male, Middle Aged, Young Adult, Diagnostic Tests, Routine methods, Lymphadenopathy diagnosis, Lymphoma diagnosis
- Abstract
Purpose: Lymphomas often present a diagnostic challenge, and for some a delay in diagnosis can negatively influence outcomes of therapy. We established a nurse practitioner-led lymphoma rapid diagnosis clinic (LRDC) with the goal of reducing wait times to definitive diagnosis. We examined the initial 30-month experience of the LRDC, and results were compared with time periods before implementation of the clinic to determine program impact., Methods: All patients referred to LRDC with suspicion of lymphoma from June 1, 2015 to Nov 30, 2017 were evaluated. Time from initial consultation to diagnosis was compared with patients diagnosed at our center with lymphoma in 2008 and 2012. Patient symptoms and relevant laboratory/imaging findings were collected to identify patterns of presentation and predictive factors for benign diagnoses., Results: Of the 126 patients evaluated, 66 (52%) had confirmation of lymphoma diagnosis. Median time to lymphoma diagnosis was 16 days for patients assessed in LRDC and 28 days for historical controls ( P < .001). By univariable analysis, lymph node size greater than 3.4 cm and presence of mediastinal or abdominal adenopathy increased the likelihood of a diagnosis of malignancy, whereas younger age, being a nonsmoker, and prior rheumatologic condition were associated with a nonmalignant diagnosis. In multivariable analysis, lymph node size, age, and prior rheumatologic diagnosis remained significant., Conclusion: Establishing a nurse practitioner-led LRDC was effective in shortening time to diagnosis of lymphoma. Younger age, smaller lymph node size, and prior rheumatologic disorder reduced the likelihood of a cancer diagnosis in our patient population.
- Published
- 2020
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32. Development and Validation of a Score to Predict Acute Care Use After Initiation of Systemic Therapy for Cancer.
- Author
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Grant RC, Moineddin R, Yao Z, Powis M, Kukreti V, and Krzyzanowska MK
- Subjects
- Adult, Aged, Databases, Factual, Female, Humans, Logistic Models, Male, Middle Aged, Ontario, Retrospective Studies, Antineoplastic Agents therapeutic use, Emergency Service, Hospital statistics & numerical data, Hospitalization statistics & numerical data, Neoplasms drug therapy, Risk Assessment methods
- Abstract
Importance: Emergency department visits and hospitalizations after starting systemic therapy for cancer are frequent, undesirable, and costly. A score to quantify the risk of needing acute care can inform decision-making and facilitate the development of preventive interventions., Objective: To develop and validate a score to predict early use of acute care after initiating systemic therapy for cancer., Design, Setting, and Participants: A retrospective population-based cohort study was conducted between July 1, 2014, and June 30, 2015. Patients with cancer were eligible if they started a new systemic therapy for cancer, regardless of line of therapy. A total of 12 162 patients in Southwestern Ontario, Canada, formed the development cohort and 15 845 patients in Northeastern Ontario formed the validation cohort. Data analysis was conducted from December 1, 2016, to August 10, 2019., Exposures: The Prediction of Acute Care Use During Cancer Treatment (PROACCT) score was created based on logistic regression in the development cohort. Combinations of cancer type and regimens were grouped into quintiles based on risk of needing acute care. The score was assessed in the validation cohort., Main Outcomes and Measures: At least 1 emergency department visit or hospitalization within 30 days after starting systemic therapy for cancer identified from administrative databases., Results: Among the 12 162 patients in the development cohort, 6903 were women and 5259 were men (mean [SD] age, 62.9 [12.6] years); among the 15 845 patients in the validation cohort, 9025 were women and 6820 were men (mean [SD] age, 62.9 [12.6] years). Use of acute care occurred within 30 days after initiation of systemic therapy in 3039 patients (25.0%) in the development cohort and 4212 patients (26.6%) in the validation cohort. Three characteristics predicted early use of acute care and formed the PROACCT score: combination of cancer type and treatment regimen, age, and emergency department visits in the prior year (C statistic, 0.67; 95% CI, 0.66-0.69; P < .001). Other characteristics including patient-reported symptoms did not improve performance. In the validation cohort, the PROACCT score was associated with use of acute care (odds ratio per point increase, 1.22; 95% CI, 1.20-1.24; P < .001), had a C statistic of 0.61 (95% CI, 0.60-0.62; P < .001), was reasonably calibrated, and provided net benefit in decision curve analysis., Conclusions and Relevance: The PROACCT score predicted the risk of early use of acute care in patients starting systemic treatment for cancer and could be incorporated at the point of care to select patients for preventive interventions. Future studies should validate the PROACCT score in other settings.
- Published
- 2019
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33. Outcomes of patients with relapsed low-grade lymphoma retreated with rituximab are similar to rituximab naïve patients.
- Author
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Vijenthira A, Maganti M, Kukreti V, Kuruvilla J, Tiedemann R, Chen C, Crump M, and Prica A
- Subjects
- Antineoplastic Agents, Immunological administration & dosage, Antineoplastic Agents, Immunological adverse effects, Humans, Molecular Targeted Therapy, Prognosis, Rituximab administration & dosage, Rituximab adverse effects, Treatment Outcome, Antineoplastic Agents, Immunological therapeutic use, Lymphoma drug therapy, Lymphoma pathology, Rituximab therapeutic use
- Published
- 2019
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- View/download PDF
34. Addition of Cyclophosphamide "On Demand" to Lenalidomide and Corticosteroids in Patients With Relapsed/Refractory Multiple Myeloma-A Retrospective Review of a Single-center Experience.
- Author
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Alahmadi M, Masih-Khan E, Atenafu EG, Chen C, Kukreti V, Tiedemann R, Trudel S, and Reece DE
- Subjects
- Adult, Aged, Dexamethasone therapeutic use, Disease Progression, Drug Resistance, Neoplasm drug effects, Female, Humans, Lenalidomide therapeutic use, Male, Middle Aged, Multiple Myeloma mortality, Multiple Myeloma pathology, Progression-Free Survival, Recurrence, Retrospective Studies, Treatment Outcome, Antineoplastic Agents, Alkylating therapeutic use, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Cyclophosphamide therapeutic use, Multiple Myeloma drug therapy
- Abstract
Introduction: The combination of lenalidomide and dexamethasone (Len-Dex) is an established regimen for patients with relapsed or refractory myeloma. To prolong the benefit of this effective regimen, the Myeloma Program at Princess Margaret Cancer Centre has routinely added a third agent, oral cyclophosphamide (Cy) given weekly, to Len-Dex at disease progression., Patients and Methods: In the present report, we describe the cases of 53 patients who had received Len-Dex-Cy for a minimum of 4 weeks from January 2007 to December 2014 after progression with Len-Dex alone. The dose of added Cy ranged from 250 to 500 mg weekly. The median number of previous regimens, including Len-Dex, was 2 (range, 2-4); 80% of patients had undergone previous autologous stem cell transplantation., Results: The overall rate of response equal to or greater than a partial response was 34%, and clinical benefit (stable disease or better) was observed in 87% of the patients. The median duration of Len-Dex-Cy therapy was 6.9 months (range, 0.9-55.1 months). The median progression-free survival was 6.1 months (range, 4.2-8.1 months) from the addition of Cy and 24.1 months (range, 15.9-32.0 months) from start of Len-Dex., Conclusion: The addition of Cy for patients with myeloma developing progression with Len-Dex was an inexpensive option with manageable toxicity that resulted in a clinically meaningful extension of disease control., (Copyright © 2018. Published by Elsevier Inc.)
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- 2019
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35. Ambulatory Toxicity Management (AToM) Pilot: results of a pilot study of a pro-active, telephone-based intervention to improve toxicity management during chemotherapy for breast cancer.
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Krzyzanowska MK, MacKay C, Han H, Eberg M, Gandhi S, Laferriere NB, Powis M, Howell D, Atzema CL, Chan KKW, Kukreti V, Mitchell S, Nayer M, Pasetka M, Knittel-Keren D, and Redwood E
- Abstract
Background: Chemotherapy is associated with a significant risk of toxicity, which often peaks between ambulatory visits to the cancer centre. Remote symptom management support is a tool to optimize self-management and healthcare utilization, including emergency department visits and hospitalizations (ED+H) during chemotherapy. We performed a single-arm pilot study to evaluate the feasibility, acceptability, and potential impact of a telephone symptom management intervention on healthcare utilization during chemotherapy for early stage breast cancer (EBC)., Methods: Women starting adjuvant or neoadjuvant chemotherapy for EBC at two cancer centres in Ontario, Canada, received standardized, nurse-led calls to assess common toxicities at two time points following each chemotherapy administration. Feasibility outcomes included patient enrollment, retention, RN adherence to delivering calls per the study schedule, and resource use associated with calls; acceptability was evaluated based on patient and provider feedback. Impact on acute care utilization was evaluated post hoc by linking individual patient records to provincial data holdings to examine ED+H patterns among participating patients compared to contemporaneous controls., Results: Between September 2013 and December 2014, 77 women were enrolled (mean age 55 years). Most commonly used regimens were AC-paclitaxel (58%) and FEC-docetaxel (16%); 78% of patients received primary granulocyte colony-stimulating factor prophylaxis. 83.8% of calls were delivered per schedule; mean call duration was 9 min. The intervention was well received by both patients and clinicians. Comparison of ED+H rates among study participants versus controls showed that there were fewer ED visits in intervention patients [incidence rate ratio (IRR) (95% CI) = 0.54 (0.36, 0.81)] but no difference in the rate of hospitalizations [IRR (95% CI) = 1.02 (0.59, 1.77)]. Main implementation challenges included identifying eligible patients, fitting the calls into existing clinical responsibilities, and effective communication to the patient's clinical team., Conclusions: Telephone-based pro-active toxicity management during chemotherapy is feasible, perceived as valuable by clinicians and patients, and may be associated with lower rates of acute care use. However, attention must be paid to workflow issues for scalability. Larger scale evaluation of this approach is in progress., Competing Interests: Approval from the institutional research ethics boards at both participating centres was received prior to initiating the study. Patients provided individual, written consent to participate in the study. In addition, patients provided consent to link their study records to provincial administrative healthcare data holdings to evaluate the impact of the intervention on ED+H.Aspects of this work have been presented at the American Society of Clinical Oncology Quality Care Symposium, Phoenix, AZ (February 2016); the Applied Research in Cancer Control Conference, Toronto, Ontario (May 2016); and the Multinational Association of Supportive Care in Cancer, Adelaide, Australia (June 2016).Authors Cassandra MacKay, Heekyung Han, Maria Eberg, and Erin Redwood are or were employees of Cancer Care Ontario, a not-for-profit agency of the Government of Ontario. All other authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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- 2019
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36. Publisher Correction: The evaluation of monoclonal gammopathy of renal significance: a consensus report of the International Kidney and Monoclonal Gammopathy Research Group.
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Leung N, Bridoux F, Batuman V, Chaidos A, Cockwell P, D'Agati VD, Dispenzieri A, Fervenza FC, Fermand JP, Gibbs S, Gillmore JD, Herrera GA, Jaccard A, Jevremovic D, Kastritis E, Kukreti V, Kyle RA, Lachmann HJ, Larsen CP, Ludwig H, Markowitz GS, Merlini G, Mollee P, Picken MM, Rajkumar VS, Royal V, Sanders PW, Sethi S, Venner CP, Voorhees PM, Wechalekar AD, Weiss BM, and Nasr SH
- Abstract
In the key to Figure 1 of this article, 'Amyloid microtubules' has been corrected to 'Microtubules'.
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- 2019
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37. The evaluation of monoclonal gammopathy of renal significance: a consensus report of the International Kidney and Monoclonal Gammopathy Research Group.
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Leung N, Bridoux F, Batuman V, Chaidos A, Cockwell P, D'Agati VD, Dispenzieri A, Fervenza FC, Fermand JP, Gibbs S, Gillmore JD, Herrera GA, Jaccard A, Jevremovic D, Kastritis E, Kukreti V, Kyle RA, Lachmann HJ, Larsen CP, Ludwig H, Markowitz GS, Merlini G, Mollee P, Picken MM, Rajkumar VS, Royal V, Sanders PW, Sethi S, Venner CP, Voorhees PM, Wechalekar AD, Weiss BM, and Nasr SH
- Subjects
- Biomarkers blood, Biopsy, Genetic Testing, Humans, Kidney Diseases blood, Kidney Diseases genetics, Kidney Diseases pathology, Paraproteinemias blood, Paraproteinemias genetics, Paraproteinemias pathology, Kidney Diseases diagnosis, Paraproteinemias diagnosis
- Abstract
The term monoclonal gammopathy of renal significance (MGRS) was introduced by the International Kidney and Monoclonal Gammopathy Research Group (IKMG) in 2012. The IKMG met in April 2017 to refine the definition of MGRS and to update the diagnostic criteria for MGRS-related diseases. Accordingly, in this Expert Consensus Document, the IKMG redefines MGRS as a clonal proliferative disorder that produces a nephrotoxic monoclonal immunoglobulin and does not meet previously defined haematological criteria for treatment of a specific malignancy. The diagnosis of MGRS-related disease is established by kidney biopsy and immunofluorescence studies to identify the monotypic immunoglobulin deposits (although these deposits are minimal in patients with either C3 glomerulopathy or thrombotic microangiopathy). Accordingly, the IKMG recommends a kidney biopsy in patients suspected of having MGRS to maximize the chance of correct diagnosis. Serum and urine protein electrophoresis and immunofixation, as well as analyses of serum free light chains, should also be performed to identify the monoclonal immunoglobulin, which helps to establish the diagnosis of MGRS and might also be useful for assessing responses to treatment. Finally, bone marrow aspiration and biopsy should be conducted to identify the lymphoproliferative clone. Flow cytometry can be helpful in identifying small clones. Additional genetic tests and fluorescent in situ hybridization studies are helpful for clonal identification and for generating treatment recommendations. Treatment of MGRS was not addressed at the 2017 IKMG meeting; consequently, this Expert Consensus Document does not include any recommendations for the treatment of patients with MGRS.
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- 2019
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38. Usability Evaluation of a Mobile Phone-Based System for Remote Monitoring and Management of Chemotherapy-Related Side Effects in Cancer Patients: Mixed-Methods Study.
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Moradian S, Krzyzanowska MK, Maguire R, Morita PP, Kukreti V, Avery J, Liu G, Cafazzo J, and Howell D
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Background: As most chemotherapy is administered in the outpatient setting, patients are required to manage related side effects at home without direct support from health professionals. The Advanced Symptom Management System (ASyMS) has been developed to facilitate the remote monitoring and management of chemotherapy-related toxicity in patients with cancer, using patient-reported outcomes questionnaires and a clinician alerting system., Objective: This study aims to evaluate the usability of the ASyMS, a mobile phone-based technology, from the perspective of Canadian patients with cancer receiving chemotherapy to identify existing design, functionality, and usability issues and elicit their views, experiences, and satisfaction with the ASyMS., Methods: We used a mixed-method approach to data collection with user-based testing, a think-aloud technique, semistructured interviews, and short answer questionnaires with a purposive sample of 10 patients with cancer. Participants attended usability testing sessions at the Centre for Global eHealth Innovation, University Health Network, and performed specific tasks on the ASyMS device. The test was videorecorded and each task was timed during the test. After the usability sessions, participants completed a posttest questionnaire and participated in a semistructured qualitative interview. A thematic analysis was used to code and categorize the identified issues into themes that summarized the type and frequency of occurrence., Results: The thematic analysis generated 3 overarching themes as follows: ASyMS user-friendliness; usefulness of ASyMS (content quality and richness); and intention to use. Results from the posttest questionnaire indicated that 80% (8/10) of participants had great motivation to use the ASyMS, 70% (7/10) had positive perceptions of the successful use of the ASyMS, and all (10/10, 100%) had a positive attitude toward using the ASyMS in the future. Most identified design and functionality issues were related to the navigation of the ASyMS device and a desire for a more attractive design with advanced functionality and features. The main general design recommendations were as follows: enhance the readability of the screen; implement advance options (eg, search option); and support better navigation., Conclusions: The ASyMS has shown positive perceptions of patients in usability testing and qualitative interviews. An evaluation of the effects of the ASyMS on symptom outcomes in a clinical trial is needed., (©Saeed Moradian, Monika K. Krzyzanowska, Roma Maguire, Plinio P. Morita, Vishal Kukreti, Jonathan Avery, Geoffrey Liu, Joseph Cafazzo, Doris Howell. Originally published in JMIR Cancer (http://cancer.jmir.org), 21.12.2018.)
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- 2018
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39. Chemotherapy with stem cell transplantation is more effective than immunotherapy in sporadic late onset nemaline myopathy with monoclonal gammopathy.
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Kotchetkov R, Dyszkiewicz-Korpanty A, and Kukreti V
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- Humans, Male, Middle Aged, Myopathies, Nemaline pathology, Paraproteinemias pathology, Immunotherapy methods, Myopathies, Nemaline therapy, Paraproteinemias therapy, Stem Cell Transplantation methods
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- 2018
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40. Improving the Safety and Quality of Systemic Treatment Regimens in Computerized Prescriber Order Entry Systems.
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Crespo A, Redwood E, Vu K, and Kukreti V
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- Humans, Medical Oncology standards, Medication Therapy Management, Ontario, Patient Care Management methods, Patient Care Management standards, Pharmacy Service, Hospital, Practice Patterns, Physicians', Medical Oncology methods, Medical Order Entry Systems standards, Quality Improvement
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Purpose: Systemic treatment (ST) computerized prescriber order entry (CPOE) and preprinted orders (PPO) are proven to reduce errors. There is no known guidance in oncology to facilitate high-quality, accurate regimen development and review; hence, this was identified as a system-wide gap. This provincial initiative aimed to improve the quality of oncology regimens through a comprehensive review of systemic treatment (ST) regimens and the development of standards., Methods: A system-wide analysis of all active regimens (both CPOE and PPO) to ensure they were built as intended was conducted in 2015. Thirty-five hospitals (on behalf of 75 treatment facilities) were asked to report any unintentional discrepancies and details of the maintenance review process. Discrepancies were compiled, categorized, and analyzed for potential to cause harm. In addition, a multidisciplinary expert working group was formed to create best practice recommendations., Results: The review yielded a 94% response rate and took a total of 18 months to complete (70% completed within 9 months). The average number of regimens reviewed was 336 (range, 15 to 700; n = 9). Unintentional discrepancies were reported by nine hospitals (27%). A total of 369 discrepancies were reported (average, 55 per hospital), and 28 were deemed to have a moderate potential for harm. Only two hospitals (6%) had an established maintenance process; now, all have standard processes for review. Consensus-based recommendations for ST-CPOE and PPO regimen development and maintenance were developed., Conclusion: The review identified unintentional discrepancies and, because of the potential for patient harm, corrective action has been taken. Identified discrepancies have been amended, and standard regimen development and maintenance review processes are now implemented system-wide to improve the quality and safety of systemic treatment delivery.
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- 2018
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41. Intravenous Chemotherapy Compounding Errors in a Follow-Up Pan-Canadian Observational Study.
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Gilbert RE, Kozak MC, Dobish RB, Bourrier VC, Koke PM, Kukreti V, Logan HA, Easty AC, and Trbovich PL
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- Administration, Intravenous, Antineoplastic Agents administration & dosage, Canada epidemiology, Follow-Up Studies, Humans, Neoplasms drug therapy, Pharmacists, Pharmacy Service, Hospital standards, Risk Assessment, Risk Factors, Antineoplastic Agents adverse effects, Antineoplastic Agents chemistry, Drug Compounding, Medication Errors, Neoplasms epidemiology
- Abstract
Purpose: Intravenous (IV) compounding safety has garnered recent attention as a result of high-profile incidents, awareness efforts from the safety community, and increasingly stringent practice standards. New research with more-sensitive error detection techniques continues to reinforce that error rates with manual IV compounding are unacceptably high. In 2014, our team published an observational study that described three types of previously unrecognized and potentially catastrophic latent chemotherapy preparation errors in Canadian oncology pharmacies that would otherwise be undetectable. We expand on this research and explore whether additional potential human failures are yet to be addressed by practice standards., Methods: Field observations were conducted in four cancer center pharmacies in four Canadian provinces from January 2013 to February 2015. Human factors specialists observed and interviewed pharmacy managers, oncology pharmacists, pharmacy technicians, and pharmacy assistants as they carried out their work. Emphasis was on latent errors (potential human failures) that could lead to outcomes such as wrong drug, dose, or diluent., Results: Given the relatively short observational period, no active failures or actual errors were observed. However, 11 latent errors in chemotherapy compounding were identified. In terms of severity, all 11 errors create the potential for a patient to receive the wrong drug or dose, which in the context of cancer care, could lead to death or permanent loss of function. Three of the 11 practices were observed in our previous study, but eight were new. Applicable Canadian and international standards and guidelines do not explicitly address many of the potentially error-prone practices observed., Conclusion: We observed a significant degree of risk for error in manual mixing practice. These latent errors may exist in other regions where manual compounding of IV chemotherapy takes place. Continued efforts to advance standards, guidelines, technological innovation, and chemical quality testing are needed.
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- 2018
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42. Effectiveness and tolerability of first-line autologous stem cell transplant and maintenance rituximab for mantle cell lymphoma.
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Falcone U, Jiang H, Bashir S, Tsang R, Kukreti V, Keating A, Crump M, and Kuruvilla J
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- Adult, Aged, Female, Humans, Lymphoma, Mantle-Cell mortality, Maintenance Chemotherapy, Male, Middle Aged, Retrospective Studies, Survival Analysis, Transplantation, Autologous, Hematopoietic Stem Cell Transplantation methods, Lymphoma, Mantle-Cell therapy, Rituximab therapeutic use
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- 2018
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43. Single-center Experience in Treating Patients With t(4;14) Multiple Myeloma With and Without Planned Frontline Autologous Stem Cell Transplantation.
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Chan H, Phillips M, Maganti M, Farooki S, Piza Rodriguez G, Masih-Khan E, Chen C, Prica A, Reece D, Tiedemann R, Trudel S, and Kukreti V
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- Female, Humans, Male, Middle Aged, Multiple Myeloma mortality, Multiple Myeloma pathology, Survival Rate, Treatment Outcome, Hematopoietic Stem Cell Transplantation methods, Multiple Myeloma drug therapy, Transplantation, Autologous methods
- Abstract
Background: Translocation t(4;14) has traditionally been classified as a high-risk cytogenetic feature in patients with multiple myeloma with shortened progression-free (PFS) and overall survival (OS) despite initial response to treatment. Recent data have shown an improved long-term survival in these patients treated with novel agents, such as bortezomib., Patients and Methods: We conducted a retrospective study on our patients with t(4;14) multiple myeloma treated with bortezomib-based induction between July 1, 2006 and June 30, 2014 to assess the real-world outcomes of these patients in a tertiary center., Results: Among the 75 patients analyzed, the median PFS was 33.5 months, and the median OS was 69.6 months after a median follow-up of 41 months. Even in the era of novel agents, patients who received frontline autologous stem cell transplant had a better PFS than those who received chemotherapy alone (median PFS, 24.2 months vs. 41.5 months; P = .01). Hypercalcemia at the time of presentation was found to be a significant predictor of progression (hazard ratio [HR], 10.1; 95% confidence interval [CI], 4.0-26.0) and death (HR, 9.4; 95% CI, 3.2-27.8), and co-harboring of del(17p) by fluorescent in situ hybridization with t(4;14) was associated with a significantly inferior OS (HR, 4.0; 95% CI, 1.4-11.4)., Conclusion: Even in the era of novel agents, t(4;14) remains a negative prognostic marker. Frontline autologous stem cell transplant remains as an essential tool when treating these high-risk patients, but further prospective randomized studies are needed to determine the most effective strategy for this patient group., (Copyright © 2018 Elsevier Inc. All rights reserved.)
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- 2018
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44. Brentuximab vedotin plus bendamustine in relapsed or refractory Hodgkin's lymphoma: an international, multicentre, single-arm, phase 1-2 trial.
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O'Connor OA, Lue JK, Sawas A, Amengual JE, Deng C, Kalac M, Falchi L, Marchi E, Turenne I, Lichtenstein R, Rojas C, Francescone M, Schwartz L, Cheng B, Savage KJ, Villa D, Crump M, Prica A, Kukreti V, Cremers S, Connors JM, and Kuruvilla J
- Subjects
- Academic Medical Centers, Adolescent, Adult, Aged, Bendamustine Hydrochloride therapeutic use, Brentuximab Vedotin, Confidence Intervals, Disease-Free Survival, Female, Hodgkin Disease diagnosis, Humans, Immunoconjugates therapeutic use, Internationality, Kaplan-Meier Estimate, Lymphoma, Large-Cell, Anaplastic diagnosis, Male, Middle Aged, New York City, Prognosis, Risk Assessment, Salvage Therapy methods, Single-Blind Method, Survival Analysis, Treatment Outcome, Young Adult, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Hodgkin Disease drug therapy, Hodgkin Disease mortality, Lymphoma, Large-Cell, Anaplastic drug therapy, Lymphoma, Large-Cell, Anaplastic mortality
- Abstract
Background: Brentuximab vedotin is currently approved for patients with relapsed or refractory Hodgkin's lymphoma who previously received an autologous stem cell transplant or two previous multiagent chemotherapy regimens, and for patients with relapsed or refractory systemic anaplastic large-T-cell lymphoma who previously received at least one chemotherapy regimen. A high proportion of patients with CD30-expressing relapsed or refractory lymphomas have durable responses to single-agent brentuximab vedotin and show longer progression-free survival than do patients treated with chemotherapy. In patients with Hodgkin's lymphoma and peripheral T-cell lymphoma, treatment with bendamustine alone only achieves modest improvements in progression-free survival compared with that for chemotherapy. The objective of this study was to explore the safety and clinical activity of the combination of brentuximab vedotin plus bendamustine in heavily pretreated patients with relapsed or refractory Hodgkin's lymphoma and anaplastic large-T-cell lymphoma., Methods: In this international, multicentre, single-arm, phase 1-2 trial, eligible patients were aged 18 years or older, had histologically confirmed relapsed or refractory Hodgkin's lymphoma or anaplastic large-T-cell lymphoma, had biopsy-proven CD30-positive tumours, had an Eastern Cooperative Oncology Group performance status of 2 or less, and received at least one previous multiagent chemotherapy regimen. In phase 1, patients were assigned following a 3+3 dose-escalation design to one of four cohorts to receive one dose of either 1·2 mg/kg or 1·8 mg/kg of brentuximab vedotin intravenously on day 1 of a 21 day cycle, plus one dose of bendamustine (70 mg/m
2 , 80 mg/m2 , or 90 mg/m2 ) on days 1 and 2 of the treatment cycle. In phase 2, all patients were assigned to receive brentuximab vedotin plus bendamustine at the recommended phase 2 dose from phase 1. The primary endpoints were maximum tolerated dose and dose-limiting toxicity for phase 1, and the proportion of patients achieving an overall response in phase 2. For both phases 1 and 2, all patients receiving at least one dose of study drug were evaluable for toxicity and all patients completing at least one cycle of therapy were evaluable for response. The study is ongoing but no longer recruiting patients. This trial is registered with ClinicalTrials.gov, number NCT01657331., Findings: Between July 26, 2012, and May 31, 2017, we enrolled and assigned 65 patients to treatment (64 [98%] with Hodgkin's lymphoma and one [2%] with anaplastic large-T-cell lymphoma; 28 [43%] during phase 1 and 37 [57%] during phase 2). In the phase 1 part, the maximum tolerated dose of the combination was not reached. Dose-limiting toxicities were observed in three (11%) of 28 patients, including grade 4 neutropenia at 1·8 mg/kg brentuximab vedotin plus 80 mg/m2 of bendamustine in two (7%) patients and diffuse rash at 1·2 mg/kg brentuximab vedotin plus 70 mg/m2 of bendamustine in one (4%) patient. The recommended phase 2 dose was deemed to be 1·8 mg/kg of brentuximab vedotin and 90 mg/m2 of bendamustine, which are the standard doses of the drugs when given as single agents. In the phase 2 part, an overall response was achieved in 29 (78% [95% CI 62-91]) of 37 patients. Serious adverse events included grade 3 lung infection in five (14%) of 37 patients in the phase 2, and grade 3-4 neutropenia in 16 (25%) of 65 patients across phases 1 and 2. There were no treatment-related deaths., Interpretation: This study shows that brentuximab vedotin plus bendamustine, with a favourable safety profile, is an active salvage regimen for heavily pretreated patients with relapsed or refractory Hodgkin's lymphoma. This salvage regimen can potentially serve as an efficacious and safe alternative to platinum-based chemotherapy before autologous stem cell transplant., Funding: Seattle Genetics, Lymphoma Research Fund of Columbia University and National Center for Advancing Translational Sciences, and National Institutes of Health., (Copyright © 2018 Elsevier Ltd. All rights reserved.)- Published
- 2018
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45. Integrated Care Planning for Cancer Patients: A Scoping Review.
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Khan AI, Arthurs E, Gradin S, MacKinnon M, Sussman J, and Kukreti V
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Introduction: There has been a growing emphasis on the use of integrated care plans to deliver cancer care. However little is known about how integrated care plans for cancer patients are developed including featured core activities, facilitators for uptake and indicators for assessing impact., Methods: Given limited consensus around what constitutes an integrated care plan for cancer patients, a scoping review was conducted to explore the components of integrated care plans and contextual factors that influence design and uptake., Results: Five types of integrated care plans based on the stage of cancer care: surgical, systemic, survivorship, palliative and comprehensive (involving a transition between stages) are described in current literature. Breast, esophageal and colorectal cancers were common disease sites. Multi-disciplinary teams, patient needs assessment and transitional planning emerged as key features. Provider buy-in and training alongside informational technology support served as important facilitators for plan uptake. Provider-level measurement was considerably less robust compared to patient and system-level indicators., Conclusions: Similarities in design features, components and facilitators across the various types of integrated care plans indicates opportunities to leverage shared features and enable a management lens that spans the trajectory of a patient's journey rather than a phase-specific silo approach to care.
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- 2017
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46. Bleomycin pulmonary toxicity does not adversely affect the outcome of patients with Hodgkin lymphoma.
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Sun HL, Atenafu EG, Tsang R, Kukreti V, Marras TK, Crump M, and Kuruvilla J
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- Adolescent, Adult, Aged, Antineoplastic Combined Chemotherapy Protocols adverse effects, Bleomycin administration & dosage, Bleomycin adverse effects, Dacarbazine administration & dosage, Doxorubicin administration & dosage, Female, Humans, Kaplan-Meier Estimate, Lung Diseases chemically induced, Lung Diseases diagnosis, Male, Middle Aged, Outcome Assessment, Health Care methods, Outcome Assessment, Health Care statistics & numerical data, Proportional Hazards Models, Retrospective Studies, Vinblastine administration & dosage, Young Adult, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Hodgkin Disease drug therapy
- Abstract
Bleomycin pulmonary toxicity (BPT) is a well-described complication of bleomycin-containing regimens. Previous data on risk factors and the impact of BPT on survival in Hodgkin lymphoma (HL) were conflicting. We reviewed 253 HL patients treated with adriamycin, bleomycin, vinblastine, dacarbazine (ABVD) at the Princess Margaret Hospital from 1999 to 2009 to examine the incidence and risk factors for BPT, and the effect of BPT on survival. BPT was defined by pulmonary symptoms, bilateral interstitial infiltrates on computed tomography, and the absence of infection. Kaplan-Meier estimates were used to compare overall survival (OS) and progression-free survival (PFS) between groups. The incidence of BPT was low (11%). Age ≥45 (OR = 2.5) and granulocyte colony-stimulating factor use (OR = 3.6) were identified as predictors of BPT on multivariable logistic models. At a follow-up of 5 years, OS and PFS were 88% and 82%, respectively. Neither BPT nor bleomycin discontinuation had significant impact on survival outcomes.
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- 2017
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47. A phase 1/2 study of the oral proteasome inhibitor ixazomib in relapsed or refractory AL amyloidosis.
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Sanchorawala V, Palladini G, Kukreti V, Zonder JA, Cohen AD, Seldin DC, Dispenzieri A, Jaccard A, Schönland SO, Berg D, Yang H, Gupta N, Hui AM, Comenzo RL, and Merlini G
- Subjects
- Administration, Oral, Aged, Boron Compounds adverse effects, Disease-Free Survival, Female, Follow-Up Studies, Glycine administration & dosage, Glycine adverse effects, Humans, Male, Middle Aged, Proteasome Inhibitors adverse effects, Survival Rate, Amyloidosis drug therapy, Amyloidosis mortality, Boron Compounds administration & dosage, Glycine analogs & derivatives, Proteasome Inhibitors administration & dosage
- Abstract
This phase 1/2 study assessed the safety, tolerability, and preliminary efficacy of the oral proteasome inhibitor (PI) ixazomib in patients with relapsed/refractory immunoglobulin light chain (AL) amyloidosis. Ixazomib was administered to adult patients with relapsed/refractory AL amyloidosis after 1 or more prior lines of therapy (including bortezomib) on days 1, 8, and 15 of 28-day cycles, for up to 12 cycles. Patients with less than partial response after 3 cycles received oral dexamethasone (40 mg, days 1-4) from cycle 4. A 3+3 dose-escalation phase was followed by 2 expansion cohorts (PI-naive and PI-exposed patients) at the maximum tolerated dose (MTD). Twenty-seven patients were enrolled: 11 during dose escalation (6 at 4.0 mg and 5 at 5.5 mg) and 16 during dose expansion (4.0 mg). Three patients experienced dose-limiting toxicities: 1 at 4.0 mg and 2 at 5.5 mg; the MTD was determined as 4.0 mg. Most common adverse events (AEs) included nausea, skin and subcutaneous tissue disorders (SSTD), diarrhea, and fatigue; grade 3 or higher AEs included dyspnea, fatigue, and SSTD. Overall, the hematologic response rate was 52% in patients treated at the MTD (n = 21). Organ responses were seen in 56% of patients (5 cardiac, 5 renal). Median hematologic progression-free survival was 14.8 months; 1-year progression-free and overall survival rates were 60% and 85%, respectively (median follow-up, 16.9 months). Weekly oral ixazomib appears to be active in patients with relapsed/refractory AL amyloidosis, with a generally manageable safety profile. The study was registered at clinicaltrials.gov as #NCT01318902 A phase 3 study is ongoing (#NCT01659658)., (© 2017 by The American Society of Hematology.)
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- 2017
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48. Secondary primary malignancies during the lenalidomide-dexamethasone regimen in relapsed/refractory multiple myeloma patients.
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Kotchetkov R, Masih-Khan E, Chu CM, Atenafu EG, Chen C, Kukreti V, Trudel S, Tiedemann R, and Reece DE
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- Adult, Aged, Aged, 80 and over, Female, Humans, Incidence, Lenalidomide, Male, Middle Aged, Thalidomide therapeutic use, Treatment Outcome, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Dexamethasone therapeutic use, Multiple Myeloma drug therapy, Neoplasm Recurrence, Local drug therapy, Neoplasms, Second Primary epidemiology, Thalidomide analogs & derivatives
- Abstract
Lenalidomide in combination with dexamethasone (Len-dex) represents a highly effective treatment in relapsed/refractory multiple myeloma (RRMM) patients. However, an increased risk of secondary primary malignancies (SPMs), including myelodysplastic syndrome (MDS) and acute myelogenous leukemia (AML) has been described in patients receiving lenalidomide. In order to assess the incidence and features of this complication, we reviewed 195 patients with RRMM treated with Len-dex at our institution. The median follow-up time from diagnosis of MM was 73 months (10-234 months) and from initiation of Len-dex was 19 months (1-104 months). The median duration of Len-dex for all patients was 7.8 months (range 1-90 months). The incidence rate (IR) for all SPMs from start of Len-dex was 2.37 per 100 patient-years, which reflected an IR of 1.29 for MDS/AML and 1.08 for nonhematologic malignancies (NHM). MDS was the most common SPM noted. The cumulative IR of SPM at 5 years was 1.54% from the time of MM diagnosis and 5.24% from starting Len-dex. Multivariable cumulative incidence of SPM analysis identified older age (P = 0.005) and prior number of regimens (P = 0.026) as adverse risk factors. We found more concomitant G-CSF use (P = 0.029) in patients with MDS/AML, however, causal association is not clear. The progression-free survival after Len-dex was the longest for patients in MDS/AML group, and the 5-year overall survival did not differ among groups. Although the rate of SPM was relatively low with Len-dex, concomitant G-CSF should be used judiciously and patients receiving this regimen should be observed for the development of this complication., (© 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)
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- 2017
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49. Carfilzomib significantly improves the progression-free survival of high-risk patients in multiple myeloma.
- Author
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Avet-Loiseau H, Fonseca R, Siegel D, Dimopoulos MA, Špička I, Masszi T, Hájek R, Rosiñol L, Goranova-Marinova V, Mihaylov G, Maisnar V, Mateos MV, Wang M, Niesvizky R, Oriol A, Jakubowiak A, Minarik J, Palumbo A, Bensinger W, Kukreti V, Ben-Yehuda D, Stewart AK, Obreja M, and Moreau P
- Subjects
- Adolescent, Adult, Aged, Dexamethasone administration & dosage, Disease-Free Survival, Female, Humans, Lenalidomide, Male, Middle Aged, Oligopeptides administration & dosage, Recurrence, Risk Factors, Survival Rate, Thalidomide administration & dosage, Thalidomide analogs & derivatives, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Multiple Myeloma drug therapy, Multiple Myeloma mortality
- Abstract
The presence of certain high-risk cytogenetic abnormalities, such as translocations (4;14) and (14;16) and deletion (17p), are known to have a negative impact on survival in multiple myeloma (MM). The phase 3 study ASPIRE (N = 792) demonstrated that progression-free survival (PFS) was significantly improved with carfilzomib, lenalidomide, and dexamethasone (KRd), compared with lenalidomide and dexamethasone (Rd) in relapsed MM. This preplanned subgroup analysis of ASPIRE was conducted to evaluate KRd vs Rd by baseline cytogenetics according to fluorescence in situ hybridization. Of 417 patients with known cytogenetic risk status, 100 patients (24%) were categorized with high-risk cytogenetics (KRd, n = 48; Rd, n = 52) and 317 (76%) were categorized with standard-risk cytogenetics (KRd, n = 147; Rd, n = 170). For patients with high-risk cytogenetics, treatment with KRd resulted in a median PFS of 23.1 months, a 9-month improvement relative to treatment with Rd. For patients with standard-risk cytogenetics, treatment with KRd led to a 10-month improvement in median PFS vs Rd. The overall response rates for KRd vs Rd were 79.2% vs 59.6% (high-risk cytogenetics) and 91.2% vs 73.5% (standard-risk cytogenetics); approximately fivefold as many patients with high- or standard-risk cytogenetics achieved a complete response or better with KRd vs Rd (29.2% vs 5.8% and 38.1% vs 6.5%, respectively). KRd improved but did not abrogate the poor prognosis associated with high-risk cytogenetics. This regimen had a favorable benefit-risk profile in patients with relapsed MM, irrespective of cytogenetic risk status, and should be considered a standard of care in these patients. This trial was registered at www.clinicaltrials.gov as #NCT01080391., (© 2016 by The American Society of Hematology.)
- Published
- 2016
- Full Text
- View/download PDF
50. A pharmacokinetics and safety phase 1/1b study of oral ixazomib in patients with multiple myeloma and severe renal impairment or end-stage renal disease requiring haemodialysis.
- Author
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Gupta N, Hanley MJ, Harvey RD, Badros A, Lipe B, Kukreti V, Berdeja J, Yang H, Hui AM, Qian M, Zhang X, Venkatakrishnan K, and Chari A
- Subjects
- Administration, Oral, Adult, Aged, Aged, 80 and over, Anemia etiology, Blood Proteins metabolism, Boron Compounds administration & dosage, Boron Compounds metabolism, Drug Dosage Calculations, Female, Glycine administration & dosage, Glycine metabolism, Glycine pharmacokinetics, Humans, Kidney Failure, Chronic therapy, Male, Middle Aged, Multiple Myeloma complications, Protease Inhibitors administration & dosage, Renal Dialysis, Boron Compounds pharmacokinetics, Glycine analogs & derivatives, Multiple Myeloma drug therapy, Protease Inhibitors pharmacokinetics, Renal Insufficiency therapy
- Abstract
Renal impairment (RI) is a major complication of multiple myeloma (MM). This study aimed to characterize the single-dose pharmacokinetics (PK) of the oral proteasome inhibitor, ixazomib, in cancer patients with normal renal function [creatinine clearance (CrCl) ≥90 ml/min; n = 20), severe RI (CrCl <30 ml/min; n = 14), or end-stage renal disease requiring haemodialysis (ESRD; n = 7). PK and adverse events (AEs) were assessed after a single 3 mg dose of ixazomib. Ixazomib was highly bound to plasma proteins (~99%) in all renal function groups. Unbound and total systemic exposures of ixazomib were 38% and 39% higher, respectively, in severe RI/ESRD patients versus patients with normal renal function. Total ixazomib concentrations were similar in pre- and post-dialyser samples collected from ESRD patients; therefore, ixazomib can be administered without regard to haemodialysis timing. Except for anaemia, the incidence of the most common AEs was generally similar across groups, but grade 3 and 4 AEs were more frequent in the severe RI/ESRD groups versus the normal group (79%/57% vs. 45%), as were serious AEs (43%/43% vs. 15%). The PK and safety results support a reduced ixazomib dose of 3 mg in patients with severe RI/ESRD., (© 2016 The Authors. British Journal of Haematology published by John Wiley & Sons Ltd.)
- Published
- 2016
- Full Text
- View/download PDF
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