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Half of older patients with diffuse large B-cell lymphoma (DLBCL) receiving curative-intent treatment are frail. Understanding differences in healthcare utilization including costs between frail and non-frail patients can inform appropriate models of care. A retrospective cohort study was conducted using population-based data in Ontario, Canada. Patients >66 years with DLBCL who received frontline curative-intent chemo-immunotherapy between 2006-2017 were included. Frailty was defined using a cumulative deficit-based frailty index. Healthcare utilization and costs were grouped into five phases: (1) 90 days preceding first treatment; (2) early treatment (0 to +90 days after starting treatment); (3) late treatment (+91 to +180 days); (4) follow-up (+181 to -181 days prior to death); (5) end-of-life (last 180 days before death). Costs were standardized to 30-day intervals (2019 Canadian dollars). 5,527 patients were included (median age 75 years (IQR 70-80), 48% female). 2,699 (49%) patients were classified as frail. Median costs (IQR) for frail vs. non-frail patients per 30-days based on phase of care were: (1)$5,683 (3,065-10,322) vs. $2,586 (1,656-4,721); (2)$13,090 (10,385-16,809) vs. $11,256 (9,107-13,976); (3)$5,734 (3,347-8,904) vs. $4,883 (2,845-7,543; (4)$1,138 (552-2,397) vs. $686 (350-1,425); (5)$11,413 (5,845-21,381) vs. $9,089 (4,844-15,793), p<0.0001 in all phases. In multivariable modelling, frail patients had higher rates of emergency department visits and hospitalizations and increased costs compared to non-frail patients through all phases except end-of-life. During end-of-life, a substantial portion of patients [84% (N=2569)] required admission to hospital; 27% (N=684) of whom required ICU admission. Future work could assess whether certain hospitalizations are preventable, particularly for patients identified as frail., (Copyright © 2024 American Society of Hematology.)

The prevalence of frailty in clinical trials of lymphoma is unknown. We conducted a secondary analysis of the phase III LY.12 trial in which patients with relapsed aggressive non-Hodgkin lymphoma were randomized to different salvage regimens before autologous stem cell transplant. The primary objective was to construct a lymphoma clinical trials-specific frailty index (LyFI) using previously described methods. The secondary objective was to describe the association of frailty withover all and event-free survival (OS, EFS). The LyFI was constructed using 619 patients, and11% ( N  = 70) were classified as frail. Frailty was associated with EFS (HR 1.94, 95%CI 1.53-2.46) and OS (HR 2.01, 95%CI 1.57-2.58) in univariable analysis, but was only significant as a continuous (not binary) variable in multivariable analysis controlling for prognostic score, suggesting limitations of a FI in this trial population. Future work could validate the FI using clinical assessments and/or apply it to an older trial population.

Purpose: Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare cancer, and large international cooperative efforts are needed to evaluate the significance of clinical risk factors and immunoarchitectural patterns (IAPs) for all stages of pediatric and adult patients with NLPHL., Methods: Thirty-eight institutions participated in the Global nLPHL One Working Group retrospective study of NLPHL cases from 1992 to 2021. We measured progression-free survival (PFS), overall survival (OS), transformation rate, and lymphoma-specific death rate. We performed uni- and multivariable (MVA) Cox regression stratified by management to select factors for the lymphocyte-predominant international prognostic score (LP-IPS) validated by five-fold cross-validation., Results: We identified 2,243 patients with a median age of 37 years (IQR, 23-51). The median follow-up was 6.3 years (IQR, 3.4-10.8). Most had stage I to II (72.9%) and few B symptoms (9.9%) or splenic involvement (5.4%). IAP was scored for 916 (40.8%). Frontline management included chemotherapy alone (32.4%), combined modality therapy (30.5%), radiotherapy alone (24.0%), observation after excision (4.6%), rituximab alone (4.0%), active surveillance (3.4%), and rituximab and radiotherapy (1.1%). The PFS, OS, transformation, and lymphoma-specific death rates at 10 years were 70.8%, 91.6%, 4.8%, and 3.3%, respectively. On MVA, IAPs were not associated with PFS or OS, but IAP E had higher risk of transformation (hazard ratio [HR], 1.81; P < .05). We developed the LP-IPS with 1 point each for age ≥45 years, stage III-IV, hemoglobin <10.5 g/dL, and splenic involvement. Increasing LP-IPS was significantly associated with worse PFS (HR, 1.52) and OS (HR, 2.31) and increased risk of lymphoma-specific death (HR, 2.63) and transformation (HR, 1.41)., Conclusion: In this comprehensive study of all ages of patients with NLPHL, we develop the LP-IPS to identify high-risk patients and inform upcoming prospective clinical trials evaluating de-escalation of therapy for patients with low LP-IPS scores (<2).

Purpose: Primary Mucosa-associated lymphoid tissue (MALT) lymphoma is a rare diagnosis in the breast, and clinical diagnosis based on radiological features is often challenging. This study aimed to evaluate the clinicopathological, and radiological characteristics of the patients diagnosed with primary breast MALT lymphoma., Methods: This study examined 18 cases of primary MALT lymphoma of the breast diagnosed at a single tertiary center between January 2002 to December 2020. Medical charts, radiological imaging and original pathology slides were reviewed for each case., Results: All cases were female (gender assigned at birth) and presented with a palpable mass or an incidental imaging finding. Imaging presentation ranged from mammographic asymmetries, circumscribed masses, and ultrasound masses lacking suspicious features. Seventeen cases were biopsied under ultrasound; one received a diagnostic excision biopsy. Microscopic examination of the breast specimens demonstrated atypical small lymphocyte infiltration with plasmacytoid differentiation and rare lymphoepithelial lesions. Immunohistochemistry was performed in all cases and established the diagnosis. Most patients were treated with radiotherapy, and only three were treated with chemotherapy. The median follow-up period was 4 years and 7.5 months, and all patients were alive at the last follow-up., Conclusion: Primary MALT breast lymphomas are usually indolent and non-systemic, and local radiotherapy may effectively alleviate local symptoms. Radiological findings show overlap with benign morphological features, which can delay the diagnosis of this unusual etiology. Although further studies involving a larger cohort could help establish the clinical and radiological characteristics of primary breast MALT lymphomas, pathology remains the primary method of diagnosis., Trial Registration Number: University Health Network Ethics Committee (CAPCR/UHN REB number 19-5844), retrospectively registered., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The treatment pattern and outcomes in patients with indolent B-cell lymphoma treated during the coronavirus disease 2019 (COVID-19) pandemic period compared to the prepandemic period are unclear. This was a retrospective population-based study using administrative databases in Ontario, Canada (follow-up to 31 March 2022). The primary outcome was treatment pattern; secondary outcomes were death, toxicities, healthcare utilization (emergency department [ED] visit, hospitalization) and SARS-CoV-2 outcomes. Adjusted hazard ratios (aHR) from Cox proportional hazards models were used to estimate associations. We identified 4143 patients (1079 pandemic, 3064 prepandemic), with a median age of 69 years. In both time periods, bendamustine (B) + rituximab (BR) was the most frequently prescribed regimen. During the pandemic, fewer patients received R maintenance or completed the full 2-year course (aHR 0.81, 95% CI 0.71-0.92, p = 0.001). Patients treated during the pandemic had less healthcare utilization (ED visit aHR 0.77, 95% CI 0.68, 0.88, p < 0.0001; hospitalization aHR 0.81, 95% CI 0.70-0.94, p = 0.0067) and complications (infection aHR 0.69, 95% CI 0.57-0.82, p < 0.0001; febrile neutropenia aHR 0.66, 95% CI 0.47-0.94, p = 0.020), with no difference in death. Independent of vaccination, active rituximab use was associated with a higher risk of COVID-19 complications. Despite similar front-line regimen use, healthcare utilization and admissions for infection were less in the pandemic cohort., (© 2023 British Society for Haematology and John Wiley & Sons Ltd.)

Background: The optimal hemoglobin (Hb) threshold for red blood cell transfusions in adult patients with myelodysplastic syndromes (MDS) has not been defined., Study Design and Methods: We conducted a pilot randomized multi-center study of two transfusion algorithms (liberal, to maintain Hb 110-120 g/L, transfuse 2 units if Hb < 105 g/L and 1 unit if Hb 105-110 g/L vs. restrictive, 85-105 g/L, transfuse 2 units when Hgb < 85 g/L). Primary objectives were 70% compliance in maintaining the q2 week hemoglobin within the targeted range and the achievement of a 15 g/L difference in pre-transfusion Hb. Secondary outcomes included measures of quality of life (QOL), iron studies and safety., Results: Twenty-eight patients were randomized between February 2015-2020, 13 to the restrictive arm and 15 to the liberal arm in three tertiary care centers. The compliance was 66% and 45% and the mean pre-transfusion Hb thresholds were 86 (standard deviation [SD] 8) and 98 g/L (SD 10) in the restrictive and liberal arms, (mean difference 11.8 g/L, p < .0001), respectively. Patients in the liberal arm experienced a mean of 3.4 (SD 2.6) more transfusion visits and received a mean of 5.3 (SD 5.5) more units of blood during the 12-week study. Ferritin increased by 1043 (SD 1516) IU/L and 148 (SD 1319) IU/L in the liberal and restrictive arms, respectively. Selected QOL scores were superior pre-transfusion and more patients achieved clinically important improvements in the liberal arm compared with the restrictive arm for selected symptoms and function domains., Conclusion: The results establish that policies for transfusion support can be delivered in practice at multiple hospitals, but further research is required to understand the full clinical effects and safety of liberal transfusion policies in MDS outpatients., (© 2024 AABB.)

The standard treatment for Diffuse Large B-Cell Lymphoma (DLBCL) is rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (RCHOP). However, many patients require subsequent treatment after relapsed disease. The ABC subtype of DLBCL (ABC-DLBCL) has a worse prognosis, and the PHOENIX trial explored adding ibrutinib to RCHOP for this patient population. The trial showed favorable outcomes for younger patients, and our study aimed to inform clinical decision-making via a cost-effectiveness model to compare RCHOP with and without ibrutinib (I-RCHOP). A Markov decision analysis model was designed to compare the treatments for patients younger than 60 years with ABC-DLBCL. The model considered treatment pathways, adverse events, relapses, and death, incorporating data on salvage treatments and novel therapies. The results indicated that I-RCHOP was more cost-effective, with greater quality-adjusted life years (QALY, 15.48 years vs. 14.25 years) and an incremental cost-effectiveness ratio (ICER) of CAD 34,111.45/QALY compared to RCHOP only. Sensitivity analyses confirmed the model's robustness. Considering the high market price for ibrutinib, I-RCHOP may be more costly. However, it is suggested as the preferred cost-effective strategy for younger patients due to its benefits in adverse events, overall survival, and quality of life. The decision analytic model provided relevant and robust results to inform clinical decision-making.

Background: Hematopoietic cell transplantation (HCT) is an established therapy for hematologic malignancies and serious non-malignant blood disorders. Despite its curative potential, HCT is associated with substantial toxicity and health resource utilization. Effective delivery of HCT requires complex hospital-based care, which limits the number of HCT centres in Canada. In Canada, the quantity, indications, temporal trends, and outcomes of patients receiving HCT are not known. Methods: A retrospective cohort study of first transplants reported to the Cell Therapy Transplant Canada (CTTC) registry between 2000 and 2019. We determined overall survival (OS) and non-relapse mortality (NRM), categorizing the cohort into early (2000-2009) and later (2010-2019) eras to investigate temporal changes. Results: Of 18,046 transplants, 7571 were allogeneic and 10,475 were autologous. Comparing the two eras, allogeneic transplants increased in number by 22.3%, with greater use of matched unrelated donors in the later era. Autologous transplants increased by 10.9%. Temporal improvements in NRM were observed in children and adults. OS improved in pediatric patients and in adults receiving autologous HCT. In adults receiving allogeneic HCT, OS was stable despite the substantially older age of patients in the later era. Interpretation: HCT is an increasingly frequent procedure in Canada which has expanded to serve older adults. Noted improvements in NRM and OS reflect progress in patient and donor selection, preparation for transplant, and post-transplant supportive care. In allogeneic HCT, unrelated donors have become the most frequent donor source, highlighting the importance of the continued growth of volunteer donor registries. These results serve as a baseline measure for quality improvement and health services planning in Canada.

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 × 10 6 /kg (n = 478) achieved a shorter median progression-free survival (PFS) of 24.1m versus 34.5m in patients collecting 4.5 to 8 × 10 6 /kg (n = 129). A small group (n = 14) collecting ≤4.5 × 10 6 /kg but minimum of 2 × 10 6 /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.)

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.)

Background: Mental disorders have been reported in patients with diffuse large B-cell lymphoma (DLBCL), but studies examining their association with mortality are lacking., Methods: We conducted a population-based study using linked administrative health-care databases from Ontario, Canada. All patients with DLBCL 18 years of age or older treated with rituximab-based therapy between January 1, 2005, and December 31, 2017, were identified and followed until March 1, 2020. Mental disorders were defined as either preexisting or postdiagnosis (after lymphoma treatment initiation). Cox proportional hazards models were used to estimate the adjusted hazard ratio (HR) between mental disorders and 1-year and all-cause mortality while controlling for covariates., Results: We identified 10 299 patients with DLBCL. The median age of the cohort was 67 years; 46% of patients were female, and 28% had a preexisting mental disorder. At 1-year follow-up, 892 (9%) had a postdiagnosis mental disorder, and a total of 2008 (20%) patients died. Preexisting mental disorders were not associated with 1-year mortality (adjusted HR = 1.06, 95% confidence interval [CI] = 0.96 to 1.17, P = .25), but postdiagnosis disorders were (adjusted HR = 1.51, 95% CI = 1.26 to 1.82, P = .0001). During a median follow-up of 5.2 years, 2111 (22%) patients had a postdiagnosis mental disorder, and 4084 (40%) patients died. Both preexisting and postdiagnosis mental disorders were associated with worse all-cause mortality (preexisting adjusted HR = 1.12, 95% CI = 1.04 to 1.20, P = .0024; postdiagnosis adjusted HR = 1.63, 95% CI = 1.49 to 1.79, P < .0001)., Conclusions: Patients with DLBCL and mental disorders had worse short-term and long-term mortality, particularly those with postdiagnosis mental disorders. Further studies are needed to examine mental health service utilization and factors mediating the relationship between mental disorders and inferior mortality., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background and Aims: Anthracyclines can cause cancer therapy-related cardiac dysfunction (CTRCD). We aimed to assess whether statins prevent decline in left ventricular ejection fraction (LVEF) in anthracycline-treated patients at increased risk for CTRCD., Methods: In this multicenter double-blinded, placebo-controlled trial, patients with cancer at increased risk of anthracycline-related CTRCD (per ASCO guidelines) were randomly assigned to atorvastatin 40 mg or placebo once-daily. Cardiovascular magnetic resonance (CMR) imaging was performed before and within 4 weeks after anthracyclines. Blood biomarkers were measured at every cycle. The primary outcome was post-anthracycline LVEF, adjusted for baseline. CTRCD was defined as a fall in LVEF by >10% to <53%. Secondary endpoints included left ventricular (LV) volumes, CTRCD, CMR tissue characterization, high sensitivity troponin I (hsTnI), and B-type natriuretic peptide (BNP)., Results: We randomized 112 patients (56.9 ± 13.6 years, 87 female, and 73 with breast cancer): 54 to atorvastatin and 58 to placebo. Post-anthracycline CMR was performed 22 (13-27) days from last anthracycline dose. Post-anthracycline LVEF did not differ between the atorvastatin and placebo groups (57.3 ± 5.8% and 55.9 ± 7.4%, respectively) when adjusted for baseline LVEF (P = 0.34). There were no significant between-group differences in post-anthracycline LV end-diastolic (P = 0.20) or end-systolic volume (P = 0.12), CMR myocardial edema and/or fibrosis (P = 0.06-0.47), or peak hsTnI (P ≥ 0.99) and BNP (P = 0.23). CTRCD incidence was similar (4% versus 4%, P ≥ 0.99). There was no difference in adverse events., Conclusions: In patients at increased risk of CTRCD, primary prevention with atorvastatin during anthracycline therapy did not ameliorate early LVEF decline, LV remodeling, CTRCD, change in serum cardiac biomarkers, or CMR myocardial tissue changes., Trial Registration: NCT03186404., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Bendamustine (B) with rituximab (R) has become the preferred regimen for patients with indolent lymphoma in Ontario, Canada, compared to R with cyclophosphamide, vincristine, prednisone (CVP) or cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP). We conducted a propensity-matched retrospective cohort population-based study of patients treated with R-CVP/CHOP from 2005 to 2012 and patients treated with BR from 2013 to 2018. The primary outcome was 5-year overall survival (OS), and secondary outcomes included toxicities and healthcare utilization. The 5-year OS for patients treated with BR (n = 2023) and R-CVP/CHOP (n = 2023) was 80% and 75% respectively. Treatment with BR was associated with improved OS (HR 0.79, 95% CI 0.69-0.91). During the first 9 months, patients treated with BR versus R-CVP/CHOP had a higher number of admissions for infection (22% compared to 17%, p < 0.01) and a higher number of mean ED visits (mean 1.01 ± 1.68 visits vs. 0.85 ± 1.51 visits, p < 0.01). This trend persisted for 3 years. The adjusted 5-year OS for patients 75 years and older did not differ based on treatment regimen (55.5% for BR vs. 55.4% for R-CVP/CHOP). Our study supports the use of BR for patients with indolent lymphoma requiring treatment but suggests increased risk of certain toxicities warranting careful patient selection., (© 2023 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

Purpose: Proliferation of T-follicular helper (TFH) CD4+ T cells is a postulated pathogenic mechanism for T-cell non-Hodgkin lymphomas (T-NHL). The inducible T-cell costimulator (ICOS) is highly expressed by TFH, representing a potential target. MEDI-570 is a monoclonal antibody against ICOS, which eliminates ICOS+ cells in preclinical models., Patients and Methods: We report the safety, pharmacokinetics (PK), pharmacodynamics (PD), and clinical activity of MEDI-570 in T-NHL. NCI-9930 is a phase I, first-in-human study of MEDI-570 in relapsed/refractory malignant T-NHL known to express ICOS. MEDI-570 was administered intravenously every 3 weeks for up to 12 cycles. Primary endpoints were safety, dose-limiting toxicities (DLT), and recommended phase II dose (RP2D). Secondary and exploratory endpoints included efficacy parameters and various correlative studies. This study is supported by the National Cancer Institute (NCT02520791)., Results: Twenty-three patients were enrolled and received MEDI-570 at five dose levels (0.01-3 mg/kg). Sixteen (70%) had angioimmunoblastic T-cell lymphoma (AITL); median age was 67 years (29-86) and the median prior lines of therapies was 3 (1-16). Most common grade 3 or 4 adverse events were decreased CD4+ T cells (57%), lymphopenia (22%), anemia (13%), and infusion-related reactions (9%). No DLTs were observed. The RP2D was determined at 3 mg/kg. Analysis of T-cell subsets showed reductions in CD4+ICOS+ T cells reflecting its effects on TFH cells. The response rate in AITL was 44%., Conclusions: MEDI-570 was well tolerated and showed promising clinical activity in refractory AITL. MEDI-570 resulted in sustained reduction of ICOS+ T lymphocytes., (©2023 American Association for Cancer Research.)

Purpose: The use of virtual care rapidly increased during the COVID-19 pandemic and has persisted as a routine method of care delivery. Much of the literature on virtual care in oncology has focused on solid tumors, and little is known about its application in malignant hematology., Methods: We performed a retrospective review of patients with hematologic malignancies at Princess Margaret Cancer Centre from October 2019 to March 2021 to determine the use of virtual care during this period, cost-savings associated with virtual visits, and patient satisfaction. Patient satisfaction was assessed using the Your Voice Matters survey, a provincially administered survey to evaluate patient experience., Results: Overall, 12.1% (1,122/9,295) of patients had a virtual visit during the study period (0% from October 2019 to February 2020, 36% from March to August 2020, and 30% from September 2020 to March 2021), of which 36% were in the lymphoma clinic and 46% were in the myeloma clinic. The mean two-way opportunity cost for an in-person visit was $168.00 CAD per person with public transit, and $120.40 CAD per person driving. Responses to the Your Voice Matters survey indicated that patients with a virtual visit reported that physical symptoms were discussed appropriately (mean 4.73/5), and were more likely to ask for a follow-up virtual visit compared with patients with in-person visits (mean 4.50/5 v 3.02/5, respectively; P < .01)., Conclusion: These findings suggest that virtual care may be a feasible and well-received tool for delivering care to a substantial proportion of patients with hematologic malignancies, while enabling substantial cost-savings to patients.

Bendamustine and rituximab (BR) is a preferred first-line therapy for indolent non-Hodgkin's lymphoma (iNHL) and mantle cell lymphoma (MCL); however, few reports on BR performance in elderly patients are available to date. We compared safety and efficacy of BR in patients ≥70 years (elderly) vs <70 years (younger) treated at our institution. Among 201 patients, 113 were elderly (median age: 77 years), including 38 patients ≥80 years, and 88 were younger (median age: 62 years). Elderly patients had more bone marrow involvement by lymphoma, anemia, ECOG status 3 and high-risk disease follicular lymphoma (P < .05 for all). Fifty-four percent of elderly received full dose of bendamustine vs 79.5% of younger patients. More elderly patients (54%) vs younger (43.2%) experienced treatment delay. Less elderly proceeded to rituximab maintenance. Overall, the number of adverse events per patient and transformed B-Cell lymphoma/secondary malignancies were similar between groups. Elderly patients had less febrile neutropenia, rituximab-associated infusion reactions, but more herpes zoster reactivation. There were more deaths in the elderly (37.2%) vs younger (10.2%) groups (P < .001), mainly due to non-lymphoma-related causes. With median follow-up of 42 months [4.0-97.0] disease-free survival for the elderly was similar to younger patients. There was no difference between patients <80 and ≥80 years (P = .274). In conclusion, the real-world elderly patients have more advanced disease and higher ECOG status. BR is well-tolerated; elderly patients had lower incidence of febrile neutropenia. Dose reduction and treatment delays are common, but BR efficacy was not affected even in very old patients (≥80 years)., (© 2022 UICC.)

Early-stage Hodgkin lymphoma has become one of the most curable hematologic malignancies. Depending upon the disease location, possible toxicities, and patient preference, chemotherapy alone with ABVD remains an accepted treatment modality for this disease. There remains a paucity of data regarding the longitudinal trajectory of health-related quality of life (HRQoL) in patients treated for HL. The impact of disease and treatment on HRQoL is increasingly important to understand as the number of long-term survivors increases. We report the longitudinal HRQoL using data prospectively collected from diagnosis up to 10 years post-treatment in the ABVD arm of the HD.6 randomized controlled trial for early-stage HL patients (N=169). We analyzed HRQoL using the EORTC QLQ-C30 collected at baseline, 3 months, 6 months, and 12 months after completion of chemotherapy and yearly up to year 10. Clinically and statistically significant improvements were noted for specific domains including emotional (3 months post-treatment), social (12 months post-treatment) and financial functioning (2 years post-treatment), and the specific symptom of fatigue (6 months post-treatment) during the follow-up period. To our knowledge, this is the first prospective, longitudinal analysis of HRQoL specifically among patients with early-stage HL treated with ABVD therapy alone. Although improvements were noted, sustained clinically and statistically significant improvements were noted only in select symptoms emphasizing the need to better understand and optimize HRQoL among this patient group., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: The aim of the study is to evaluate the prognostic value of a joint evaluation of PET and CT radiomics combined with standard clinical parameters in patients with HL., Methods: Overall, 88 patients (42 female and 46 male) with a median age of 43.3 (range 21-85 years) were included. Textural analysis of the PET/CT images was performed using freely available software (LIFE X). 65 radiomic features (RF) were evaluated. Univariate and multivariate models were used to determine the value of clinical characteristics and FDG PET/CT radiomics in outcome prediction. In addition, a binary logistic regression model was used to determine potential predictors for radiotherapy treatment and odds ratios (OR), with 95% confidence intervals (CI) reported. Features relevant to survival outcomes were assessed using Cox proportional hazards to calculate hazard ratios with 95% CI., Results: albumin ( p = 0.034) + ALP ( p = 0.028) + CT radiomic feature GLRLM GLNU mean ( p = 0.012) (Area under the curve (AUC): 95% CI (86.9; 100.0)-Brier score: 3.9, 95% CI (0.1; 7.8) remained significant independent predictors for PFS outcome. PET-SHAPE Sphericity ( p = 0.033); CT grey-level zone length matrix with high gray-level zone emphasis (GLZLM SZHGE mean ( p = 0.028)); PARAMS XSpatial Resampling ( p = 0.0091) as well as hemoglobin results ( p = 0.016) remained as independent factors in the final model for a binary outcome as predictors of the need for radiotherapy (AUC = 0.79)., Conclusion: We evaluated the value of baseline clinical parameters as well as combined PET and CT radiomics in HL patients for survival and the prediction of the need for radiotherapy treatment. We found that different combinations of all three factors/features were independently predictive of the here evaluated endpoints.

Purpose: Recent studies of polatuzumab vedotin and CD19 chimeric antigen receptor T-cell therapy (CAR-T) have shown significant improvements in progression-free survival over standard of care (SOC) for patients with diffuse large B-cell lymphoma. However, they are costly, and it is unclear whether these strategies, alone or combined, are cost-effective over SOC., Methods: A Markov model was constructed to compare four strategies for patients with newly diagnosed intermediate- to high-risk diffuse large B-cell lymphoma: strategy 1: polatuzumab-rituximab, cyclophosphamide, doxorubicin, and prednisone (R-CHP) plus second-line CAR-T for early relapse (< 12 months); strategy 2: polatuzumab-R-CHP plus second-line salvage therapy ± autologous stem-cell transplant; strategy 3: rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone plus second-line CAR-T for early relapse; strategy 4: SOC (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone plus second-line salvage therapy ± autologous stem-cell transplant). Transition probabilities were estimated from trial data. Lifetime costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs) were calculated from US and Canadian payer perspectives. Willingness-to-pay (WTP) thresholds of $150,000 US dollars (USD) or Canadian dollars (CAD)/QALY were used., Results: In probabilistic analyses (10,000 simulations), each strategy was incrementally more effective than the previous strategy, but also more costly. Adding polatuzumab-R-CHP to the SOC had an ICER of $546,956 (338,797-1,199,923) USD/QALY and $245,381 (151,671-573,250) CAD/QALY. Adding second-line CAR-T to the SOC had an ICER of $309,813 (190,197-694,200) USD/QALY and $303,163 (221,300-1,063,864) CAD/QALY. Simultaneously adding both polatuzumab-R-CHP and second-line CAR-T to the SOC had an ICER of $488,284 (326,765-840,157) USD/QALY and $267,050 (182,832-520,922) CAD/QALY., Conclusion: Given uncertain incremental benefits in long-term survival and high costs, neither polatuzumab-R-CHP frontline, CAR-T second-line, nor a combination are likely to be cost-effective in the United States or Canada at current pricing compared with the SOC.

Marginal zone lymphomas (MZL) are a rare, heterogenous group of lymphomas, accounting for 5-17% of indolent non-Hodgkin lymphomas in the western world. They can be further divided into three subtypes: extranodal MZL, splenic MZL, and nodal MZL. These subtypes differ in clinical presentation and behavior, which influences how they are managed. There is currently no standard of care for the treatment of MZL, owing to the difficulty in conducting phase 3 randomized trials in MZL, and the fact that there are limited data on the efficacy of therapy in individual subtypes. Treatment practices are thus largely borrowed from other indolent lymphomas and are based on patient and disease characteristics, as well as access to therapy. This review summarizes the Canadian treatment landscape for MZL and how these therapies may be sequenced in practice.

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.)

Patients with hematological malignancies (HM) are at risk of acute respiratory failure (ARF). Malnutrition, a common association with HM, has the potential to influence ICU outcomes. Geriatric nutritional risk index (G-NRI) is a score derived from albumin and weight, which reflects risk of protein-energy malnutrition. We evaluated the association between G-NRI at ICU admission and ICU mortality in HM patients with ARF. We conducted a single center retrospective study of ventilated HM patients between 2014 and 2018. We calculated G-NRI for all patients using their ICU admission albumin and weight. Our primary outcome was ICU mortality. Secondary outcomes included duration of mechanical ventilation and ICU length of stay. Two hundred eighty patients were admitted to the ICU requiring ventilation. Median age was 62 years (IQR 51-68), 42% (n = 118) were females, and median SOFA score was 11 (IQR 9-14). The most common type of HM was acute leukemia (54%) and 40% underwent hematopoietic cell transplant. Median G-NRI was 87 (IQR 79-99). ICU mortality was 51% (n = 143) with a median duration of ventilation of 4 days (IQR 2-7). Mortality across those at severe malnutrition (NRI < 83.5) was 59% (65/111) compared to 46% (76/164) across those with moderate-no risk (p = 0.047). On multivariable analysis, severe NRI (OR 2.34, 95% CI 1.04-5.27, p = 0.04) was significantly associated with ICU mortality. In this single center, exploratory study, severe G-NRI was prognostic of ICU mortality in HM patients admitted with respiratory failure., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: American Society of Clinical Oncology recommends that older adults with cancer being considered for chemotherapy receive geriatric assessment (GA) and management (GAM), but few randomized controlled trials have examined its impact on quality of life (QOL)., Patients and Methods: The 5C study was a two-group parallel 1:1 single-blind multicenter randomized controlled trial of GAM for 6 months versus usual oncologic care. Eligible patients were age 70+ years, diagnosed with a solid tumor, lymphoma, or myeloma, referred for first-/second-line chemotherapy or immunotherapy or targeted therapy, and had an Eastern Cooperative Oncology Group performance status of 0-2. The primary outcome QOL was measured with the global health scale of the European Organisation for the Research and Treatment of Cancer QOL questionnaire and analyzed with a pattern mixture model using an intent-to-treat approach (at 6 and 12 months). Secondary outcomes included functional status, grade 3-5 treatment toxicity; health care use; satisfaction; cancer treatment plan modification; and overall survival., Results: From March 2018 to March 2020, 350 participants were enrolled. Mean age was 76 years and 40.3% were female. Fifty-four percent started treatment with palliative intent. Eighty-one (23.1%) patients died. GAM did not improve QOL (global QOL of 4.4 points [95% CI, 0.9 to 8.0] favoring the control arm). There was also no difference in survival, change in treatment plan, unplanned hospitalization/emergency department visits, and treatment toxicity between groups., Conclusion: GAM did not improve QOL. Most intervention group participants received GA on or after treatment initiation per patient request. Considering recent completed trials, GA may have benefit if completed before treatment selection. The COVID-19 pandemic may have affected our QOL outcome and intervention delivery for some participants.

Intratumoral heterogeneity (ITH) provides the substrate for tumor evolution and treatment resistance, yet is remarkably understudied in lymphoma, due to the often limited amount of tissue that gets sampled during the routine diagnostic process, generally from a single nodal or extranodal site. Furthermore, the trajectory of how lymphoma, and especially non-Hodgkin lymphoma, spreads throughout the human body remains poorly understood. Here, we present a detailed characterization of ITH by applying whole-genome sequencing to spatially separated tumor samples harvested at the time of autopsy (n=24) and/or diagnosis (n=3) in three patients presenting with refractory B-cell non-Hodgkin lymphoma. Through deconvolution of bulk samples into clonal mixtures and inference of phylogenetic trees, we found evidence that polyclonal seeding underlies tumor dissemination in lymphoma. We identify mutation signatures associated with ancestral and descendant clones. In our series of patients with highly refractory lymphoma, the determinants of resistance were often harbored by founding clones, although there was also evidence of positive selection of driver mutations, likely under the influence of therapy. Lastly, we show that circulating tumor DNA is suitable for the detection of ancestral mutations but may miss a significant proportion of private mutations that can be detected in tissue. Our study clearly shows the existence of intricate patterns of regional and anatomical evolution that can only be disentangled through multi-regional tumor tissue profiling.

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.

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.)

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.)

Selinexor is a first-in-class, oral therapy that selectively inhibits nuclear export. The drug is active with an overall response rate (ORR) of approximately 30% in relapsed/refractory (r/r) non-Hodgkin lymphoma (NHL). Long-term patient follow-up has not been reported. Thirty-one NHL patients were treated between July 2012 and July 2018; 22 were evaluated for response. ORR was 32% (7/22). Two patients achieved complete remission (CR) and were alive and lymphoma-free at the end of follow-up. Fifteen patients (68%) progressed during treatment, most of them died within 3-10 months. The most common grade 3/4 adverse events were gastrointestinal and hematological. Median follow up was 50 months. Overall survival for the entire cohort was 16%. Selinexor monotherapy for r/r NHL is an active therapy with the potential for long-term disease control. It may serve as a 'bridge' to subsequent therapy. Additional studies are needed to identify predictive biomarkers and to evaluate combination approaches.

Background: The objectives of this study were to determine whether frailty is associated with survival in a population-based sample of patients with diffuse large B-cell lymphoma (DLBCL) and to describe the healthcare utilization patterns of frail versus nonfrail patients during treatment., Methods: A retrospective cohort study was conducted using population-based data in Ontario, Canada. Patients aged ≥66 years diagnosed between 2006 and 2017 with DLBCL or transformed follicular lymphoma who received first-line curative-intent chemoimmunotherapy were included. Frailty was defined using a modified version of a generalizable frailty index developed for use with Ontario administrative data. Cox regression was performed to examine the association between frailty and 1-year mortality., Results: A total of 5,527 patients were included (median age, 75 years [interquartile range, 70-80 years]; 48% female), of whom 2,699 (49%) were classified as frail. Within 1 year of first-line treatment, 32% (n=868) of frail patients had died compared with 20% (n=553) of nonfrail patients (unadjusted hazard ratio, 1.8; 95% CI, 1.6-2.0; P<.0001). Frail patients had higher healthcare utilization during treatment, with most hospitalizations related to infection and/or lymphoma. In multivariable modeling controlling for age, inpatient diagnosis, number of chemoimmunotherapy cycles received, comorbidity burden, and healthcare utilization, frailty remained independently associated with 1-year mortality (adjusted hazard ratio, 1.5; 95% CI, 1.3-1.7; P<.0001)., Conclusions: In a population-based sample of older adult patients with DLBCL receiving front-line curative-intent therapy, half were classified as frail, and their adjusted relative rate of death in the first year after starting treatment was 50% higher than that of nonfrail patients. Frailty seems to be associated with poor treatment tolerance and a higher likelihood of requiring acute hospital-based care.

Guillain-Barré syndrome (GBS) is a rare condition caused by autoimmune damage of peripheral nerves. We describe a case where a man in his 80s presented with subacute, progressive fatigue and weakness. He had received an outpatient work-up for possible haematological malignancy, but eventually presented to the emergency department for worsening weakness. A physical exam and cerebrospinal fluid analysis suggested a diagnosis of GBS. Subsequently, a pathological diagnosis of angioimmunoblastic T-cell lymphoma was made. The patient underwent intravenous immunoglobulin treatment for GBS and was started on cyclophosphamide, doxorubicin, vincristine and prednisone therapy. Prior research has suggested that incident malignancy may be associated with GBS, which may be caused by a paraneoplastic-type phenomenon, malignancy-associated immune dysregulation or an autoimmune reaction triggered by a common exposure. Clinicians should be aware of the possible association between these two conditions and should remain open minded to the possibility of non-infectious triggers for GBS., Competing Interests: Competing interests: PT reports non-financial support from Aurora, outside the submitted work. NAH, SA, HS, RW and AP have nothing to declare., (© BMJ Publishing Group Limited 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

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% (rMTV high , ≥4.4 cm 3 ) 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 rMTV 41% 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/rMTV low ; HR 1), 65% for intermediate-risk (28%; refractory disease and either DS 1-3 or DS 4-5/rMTV low ; HR 3.26), and 45% for high-risk (21%; DS 4-5/rMTV high irrespective of disease status; HR 7.61) groups. Pretransplant DS/rMTV 41% 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.)

The objective was to assess the cost-effectiveness of staging PET/CT in early-stage follicular lymphoma (FL) from the Canadian health-care system perspective. Methods: The study population was FL patients staged as early-stage using conventional CT imaging and planned for curative-intent radiation therapy (RT). A decision analytic model simulated the management after adding staging PET/CT versus using staging CT alone. In the no-PET/CT strategy, all patients proceeded to curative-intent RT as planned. In the PET/CT strategy, PET/CT information could result in an increased RT volume, switching to a noncurative approach, or no change in RT treatment as planned. The subsequent disease course was described using a state-transition cohort model over a 30-y time horizon. Diagnostic characteristics, probabilities, utilities, and costs were derived from the literature. Baseline analysis was performed using quality-adjusted life years (QALYs), costs (2019 Canadian dollars), and the incremental cost-effectiveness ratio. Deterministic sensitivity analyses were conducted, evaluating net monetary benefit at a willingness-to-pay threshold of $100,000/QALY. Probabilistic sensitivity analysis using 10,000 simulations was performed. Costs and QALYs were discounted at a rate of 1.5%. Results: In the reference case scenario, staging PET/CT was the dominant strategy, resulting in an average lifetime cost saving of $3,165 and a gain of 0.32 QALYs. In deterministic sensitivity analyses, the PET/CT strategy remained the preferred strategy for all scenarios supported by available data. In probabilistic sensitivity analysis, the PET/CT strategy was strongly dominant in 77% of simulations (i.e., reduced cost and increased QALYs) and was cost-effective in 89% of simulations (i.e., either saved costs or had an incremental cost-effectiveness ratio below $100,000/QALY). Conclusion: Our analysis showed that the use of PET/CT to stage early-stage FL patients reduces cost and improves QALYs. Patients with early-stage FL should undergo PET/CT before curative-intent RT., (© 2022 by the Society of Nuclear Medicine and Molecular Imaging.)

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.

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.)

There is increasing interest from cancer patients and their healthcare providers in the use of virtual care in routine clinical practice. In the setting of hematologic malignancy, where patients often undergo complex and immunodepleting treatments, understanding how to use virtual care safely and effectively is critically important. We aimed to describe the use of virtual care in patients with hematologic malignancies and to examine physician- and patient-reported outcomes in the form of a systematic scoping review. An electronic search of PubMed, Ovid MEDLINE, Elsevier Embase, Scopus, and EBSCO CINAHL was conducted from January 2000 to April 2021. A comprehensive search strategy was used to identify relevant articles, and data were extracted to assess the study design, population, setting, patient characteristics, virtual care platform, and study results. Studies were included if they described the use of virtual care for patients with hematologic malignancies; commentaries were excluded. Fifteen studies met the inclusion criteria after abstract and full-text review. Three studies found that app-based tools were effective in monitoring patient symptoms and triggering alerts for more urgent follow-up. Four studies described the use of phone-based interventions. Five studies found that videoconferencing, with both physicians and oncology nurses, was highly rated by patients. Emerging themes included high levels of patient satisfaction across all domains of virtual care. Provider satisfaction scores were rated lower than patient scores, with concerns about technical issues leading to challenges with virtual care. Four studies found that virtual care allowed providers to promptly respond to patient concerns, especially when patients were experiencing side-effects or had questions about their treatment. Overall, the use of virtual care in patients with hematologic malignancies appears feasible, and resulted in high patient satisfaction. Further research is needed in order to evaluate the optimal method of integrating virtual care into clinical practice.

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.)

Purpose: Ibrutinib reduces mortality in chronic lymphocytic leukemia (CLL). It increases the risk of atrial fibrillation (AF) and bleeding and there are concerns about heart failure (HF) and central nervous system ischemic events. The magnitude of these risks remains poorly quantified., Methods: Using linked administrative databases, we conducted a population-based cohort study of Ontario patients who were treated for CLL diagnosed between 2007 and 2019. We matched ibrutinib-treated patients with controls treated with chemotherapy but unexposed to ibrutinib on prior AF, age ≥ 66 years, anticoagulant exposure, and propensity for receiving ibrutinib. Study outcomes were AF-related health care contact, hospital-diagnosed bleeding, new diagnoses of HF, and hospitalizations for stroke and acute myocardial infarction (AMI). The cumulative incidence function was used to estimate absolute risks. We used cause-specific regression to study the association of ibrutinib with bleeding rates, while adjusting for anticoagulation as a time-varying covariate., Results: We matched 778 pairs of ibrutinib-treated and unexposed patients with CLL (N = 1,556). The 3-year incidence of AF-related health care contact was 22.7% (95% CI, 19.0 to 26.6) in ibrutinib-treated patients and 11.7% (95% CI, 9.0 to 14.8) in controls. The 3-year risk of hospital-diagnosed bleeding was 8.8% (95% CI, 6.5 to 11.7) in ibrutinib-treated patients and 3.1% (95% CI, 1.9 to 4.6) in controls. Ibrutinib-treated patients were more likely to start anticoagulation after the index date. After adjusting for anticoagulation as a time-varying covariate, ibrutinib remained positively associated with bleeding (HR, 2.58; 95% CI, 1.76 to 3.78). The 3-year risk of HF was 7.7% (95% CI, 5.4 to 10.6%) in ibrutinib-treated patients and 3.6% (95% CI, 2.2 to 5.4) in controls. There was no significant difference in the risk of ischemic stroke or AMI., Conclusion: Ibrutinib is associated with higher risk of AF, bleeding, and HF, but not AMI or stroke., Competing Interests: Husam Abdel-QadirEmployment: GlaxoSmithKline (I)Honoraria: Bausch Health (I), Valeant Pharmaceuticals International (I), Novartis (I), Janssen (I), ROC Skincare (I), Sanofi (I), Vivier (I)Consulting or Advisory Role: Bausch Health (I), LEO Pharma (I), Amgen Foundation (I), Procter & Gamble (I), Pfizer (I)Speakers' Bureau: Allergan (I), Biossance (I), Webber Naturals (I) Darryl LeongHonoraria: JanssenResearch Funding: Novartis Andrea PangResearch Funding: Everest Clinical Research Anca PricaHonoraria: AstraZeneca, Kite/GileadResearch Funding: Bristol Myers Squibb/Celgene Kumaraswamy NanthakumarConsulting or Advisory Role: Abbott Laboratories, BioSense WebsterResearch Funding: Abbott Laboratories, BioSense Webster Paaladinesh ThavendiranathanHonoraria: AmgenNo other potential conflicts of interest were reported.

Introduction: The Alliance A041202/CCTG CLC.2 trial demonstrated superior progression-free survival with ibrutinib-based therapy compared to chemoimmunotherapy with bendamustine-rituximab (BR) in previously untreated older patients with chronic lymphocytic leukemia. We completed a prospective trial-based economic analysis of Canadian patients to study the direct medical costs and quality-adjusted benefit associated with these therapies., Methods: Mean survival was calculated using the restricted mean survival method from randomization to the study time-horizon of 24 months. Health state utilities were collected using the EuroQOL EQ-5D instrument with Canadian tariffs applied to calculate quality-adjusted life years (QALYs). Costs were applied to resource utilization data (expressed in 2019 US dollars). We examined costs and QALYs associated ibrutinib, ibrutinib with rituximab (IR), and BR therapy., Results: A total of 55 patients were enrolled; two patients were excluded from the analysis. On-protocol costs (associated with protocol-specified resource use) were higher for patients receiving ibrutinib (mean $189,335; P < 0.0001) and IR (mean $219,908; P < 0.0001) compared to BR (mean $51,345), driven by higher acquisition costs for ibrutinib. Total mean costs (over 2-years) were $192,615 with ibrutinib, $223,761 with IR, and $55,413 with BR (P < 0.0001 for ibrutinib vs. BR and P < 0.0001 for IR vs. BR). QALYs were similar between the three treatment arms: 1.66 (0.16) for ibrutinib alone, 1.65 (0.24) for IR, and 1.66 (0.17) for BR; therefore, a formal cost-utility analysis was not conducted., Conclusions: Direct medical costs are higher for patients receiving ibrutinib-based therapies compared to chemoimmunotherapy in frontline chronic lymphocytic leukemia, with the cost of ibrutinib representing a key driver., Competing Interests: Conflict of interest Dr. Woyach has received honoraria and/or research funding from Pharmacyclics, Abbvie, and Janssen. Dr. Lam has received honoraria from Abbvie and Janssen. Dr. Owen has received honoraria from Janssen., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

This study compared the quality-adjusted effectiveness and costs of three treatment options for transplant-eligible patients with early progression (POD24) of follicular lymphoma. A Markov decision-analytic model using a 20-year time horizon was used to compare allogeneic stem cell transplant (alloSCT), autologous stem cell transplant (ASCT), and chemo-immunotherapy (O-CHOP). For second relapse/refractory disease, novel therapy use was modeled, including lenalidomide and rituximab/obinutuzumab, and PI3K inhibitors (PI3Ki). Costs were considered from a Canadian public health payer's perspective. Probabilistic analyses (10,000 simulations) demonstrated that at a willingness-to-pay threshold of $50,000, ASCT was most cost effective 60% of the time. ASCT resulted in more life years (10.2 vs. alloSCT 9.9 vs. O-CHOP 10.0) and quality-adjusted life years (7.5 vs. alloSCT 6.6 vs. O-CHOP 7.4), with the lowest direct costs ($190,128 CAD). In sensitivity analyses, the model was robust to key variables, including differing probabilities of progression, non-relapse mortality, graft-versus-host-disease (GVHD), costs of treating GVHD, costs of PI3Ki, and probability of secondary malignancy from ASCT. However, if patients were older than 65 years or their life expectancy was less than 10 years, chemo-immunotherapy was the preferred strategy. When considering cost, effectiveness, and toxicities, the preferred treatment strategy for most patients with POD24 follicular lymphoma is ASCT., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Cost-effectiveness analyses embedded within randomized trials allow for evaluation of value alongside conventional efficacy outcomes; however, collection of resource utilization data can require considerable trial resources., Methods: We re-analyzed the results from four phase III Canadian Cancer Trials Group trials that embedded cost-effectiveness analyses to determine the impact of minimizing potential cost categories on the incremental cost-effectiveness ratios. For each trial, we disaggregated total costs into component incremental cost categories and recalculated incremental cost-effectiveness ratios using (1) only the top 3 cost categories, (2) the top 5 cost categories, and (3) all cost components. Using individual trial-level data, confidence intervals for each incremental cost-effectiveness ratio simulation were generated by bootstrapping and descriptively presented with the original confidence intervals (and incremental cost-effectiveness ratios) from the publications., Results: Drug acquisition costs represented the highest incremental cost category in three trials, while hospitalization costs represented the other consistent cost driver and the top incremental cost category in the fourth trial. Recalculated incremental cost-effectiveness ratios based on fewer cost components (top 3 and top 5) did not differ meaningfully from the original published results. Based on conventional willingness-to-pay thresholds (US$50,000-US$100,000 per quality-adjusted life-year), none of the re-analyses would have changed the original perception of whether the experimental therapies were considered cost-effective., Conclusions: These results suggest that the collection of resource utilization data within cancer trials could be narrowed. Omission of certain cost categories that have minimal impact on incremental cost-effectiveness ratio, such as routine laboratory investigations, could reduce the costs and undue burden associated with the collection of data required for cancer trial cost-effectiveness analyses.

Rationale: Patients with hematologic malignancies requiring mechanical ventilation have historically experienced poor outcomes. Objectives: We aimed to determine whether body composition characteristics derived from thoracic computed tomographic (CT) imaging were associated with time to liberation from mechanical ventilation. Methods: We evaluated mechanically ventilated patients with hematological malignancies admitted between 2014 and 2018. We included patients with thoracic CT imaging completed between 1 month before and 48 hours after intensive care unit (ICU) admission. We assessed the association of carinal skeletal muscle cross-sectional area (CSA), subcutaneous fat CSA, and fat index (fat/skeletal muscle ratio) with time to liberation from mechanical ventilation within 28 days. We accounted for the competing event of death within 28 days of mechanical ventilation. Results: One hundred fifty-six patients were included; the mean age was 57 years (standard deviation 14) and 39% were female. Thirty-seven percent had received a hematopoietic stem cell transplant, and the median ratio of arterial oxygen tension/pressure to fraction of inspired oxygen was 134 mm Hg (interquartile range [IQR], 92-205). Median skeletal muscle CSA was 68 cm 2 (IQR, 54-88) and subcutaneous fat CSA was 38 cm 2 (IQR, 27-52). Forty-two percent of patients were liberated from mechanical ventilation within 28 days and 56% died in the ICU. Subcutaneous fat CSA (subdistribution hazard ratio [sHR], 0.81; 95% confidence interval [95% CI], -0.68 to 0.97) and fat index (sHR, 0.81; 95% CI, -0.68 to 0.97) were significantly associated with longer time to liberation from mechanical ventilation. Skeletal muscle CSA was not associated with time to liberation from ventilation (sHR, 1.08; 95% CI, -0.94 to 1.23). Conclusions: Body composition measurements based on thoracic CT scans were associated with time to liberation from ventilation. These could represent novel surrogate markers of physical frailty in patients with hematologic malignancies receiving mechanical ventilation.

We conducted an analysis of indirect costs alongside the LY.12 randomized trial in patients with relapsed or refractory (R/R) aggressive non-Hodgkin lymphoma (NHL). Lost productivity data for Canadian patients and caregivers in the trial were collected at baseline and with each chemotherapy cycle pre-transplant, using an adapted Lost Productivity questionnaire. Mean per patient indirect costs were CAD 2999 for patients in the GDP arm and CAD 3400 in the DHAP arm. A substantial majority was not working or had to reduce their workload during this treatment time. Salvage chemotherapy for R/R aggressive NHL is associated with significant indirect costs to patients and their caregivers.

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.)

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.)

High-dose chemotherapy and autologous stem cell transplant (ASCT) remains a cornerstone of treatment in relapsed/refractory (R/R) aggressive-histology lymphomas. This retrospective study examined efficacy and safety of peripheral blood stem cell (PBSC) mobilization using cyclophosphamide/etoposide and GCSF (CE + GCSF, n  = 129) versus gemcitabine, dexamethasone and cisplatin and GCSF (GDP + GCSF, n  = 210). All patients received first salvage with GDP. Patients mobilized with CE + GCSF required fewer days of leukapheresis (median 1 vs 2 day; p  = .001) and achieved higher total CD34+ yield than GDP + GCSF patients (8.5 vs 7.1 × 10 6 CD34+ cells/kg, p  = .001). Rates of febrile neutropenia and CD34+ collection ≥5 × 10 6 CD34+ cells/kg were similar (OR 1.19, 95% CI: 0.54-2.6, p  = .66). In multivariable analysis, days to engraftment and admission duration were not statistically different between the two mobilization strategies. While CE + GCSF appeared more efficacious for mobilization after GDP salvage, this did not translate to significant differences in clinical outcomes.