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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. [ABSTRACT FROM AUTHOR]

Objectives: Lymphocytic infiltrates in the subcutaneous adipose tissue, often accompanied by fat necrosis, are typically seen in benign panniculitis. Diagnostic considerations include subcutaneous panniculitis-like T-cell lymphoma and cutaneous γδ T-cell lymphoma, whereas a primary subcutaneous B-cell lymphoma in this setting has not been previously described. Methods: We report the case of a 72-year-old woman with multiple deep cutaneous nodules on the trunk and upper extremities. Results: During 3 years of clinical follow-up, new skin nodules developed, while existing lesions remained stable or regressed. No other organ involvement was detected. Sequential biopsy specimens of the subcutaneous lesions revealed patchy, predominantly septal, lymphocytic infiltrates associated with extensive hyaline fat necrosis. The histologic and immunophenotypic features were consistent with marginal zone lymphoma. Genotyping revealed an identical monoclonal immunoglobulin gene rearrangement across all biopsy specimens. Conclusions: This case represents, to our knowledge, the first reported case of primary subcutaneous B-cell lymphoma closely associated with panniculitis. [ABSTRACT FROM AUTHOR]

Rituximab has improved the treatment of B-cell non-Hodgkin lymphomas. While it is generally well tolerated, serious adverse effects including infusion reactions with hemodynamic compromise and cardiac arrhythmias or ischemia are possible. We report a case of coronary vasospasm occurring during a rituximab infusion in a patient with minimal tumour burden and who had no cardiac risk factors. This case highlights that determination of the cause of ischemia is important and may identify some patients who can be successfully rechallenged. [ABSTRACT FROM AUTHOR]

Summary The Canadian Cancer Trials Group (CCTG) LY.17 is an ongoing multi‐arm randomized phase II trial evaluating novel salvage therapies compared with R‐GDP (rituximab, gemcitabine, dexamethasone and cisplatin) in autologous stem cell transplantation (ASCT)‐eligible patients with relapsed/refractory diffuse large B‐cell lymphoma (RR‐DLBCL). This component of the LY.17 trial evaluated a dose‐intensive chemotherapy approach using a single cycle of inpatient R‐DICEP (rituximab, dose‐intensive cyclophosphamide, etoposide and cisplatin) to achieve both lymphoma response and stem cell mobilization, shortening time to ASCT. This report is the result of the protocol‐specified second interim analysis of the 67 patients who were randomized to either 1 cycle of R‐DICEP or to 3 cycles of R‐GDP. The overall response rate (ORR) was 65.6% for R‐DICEP and 48.6% for R‐GDP. The ASCT rate was 71.9% versus 54.3%, and 1‐year progression‐free survival rate was 42% versus 32%, respectively, for R‐DICEP versus R‐GDP. Although the improvement in ORR for R‐DICEP versus R‐GDP exceeded the pre‐specified 10% threshold to proceed to full accrual of 64 patients/arm, higher rates of grade 3–5 toxicities, and the need for hospitalization led to the decision to stop this arm of the study. CCTG LY.17 will continue to evaluate different salvage regimens that incorporate novel agents. [ABSTRACT FROM AUTHOR]

Outcomes of patients with relapsed low-grade lymphoma retreated with rituximab are similar to rituximab naïve patients Rituximab combined with chemotherapy has been shown to be superior to chemotherapy alone in patients with relapsed/refractory indolent lymphomas [[1]]. As per the regional funding guidelines, patients had to have at least a one-year treatment-free period between their first- and second-line therapies; this therefore excluded any patients who were refractory to rituximab per this definition. Maintenance rituximab use after second-line chemoimmunotherapy was associated with superior PFS (HR: 0.39 (95%CI: 0.2, 0.77), I p i =.0069), with most patients (19/26 patients, 73%) who received it being in Group 1 (NoR-R). [Extracted from the article]

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.A313 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 4.0mgand5 at 5.5mg)and 16 during doseexpansion (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. Mostcommonadverse 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 5 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. [ABSTRACT FROM AUTHOR]

Simple Summary: Cancer patients and their families require support to effectively self-manage the medical, emotional, and lifestyle consequences of cancer. In this paper, we describe a training program that showed improvement in oncology nurses confidence in the microskills required for the provision of self-management support to patients for application in routine care and in roles as cancer coaches before and after training at three cancer centres in Ontario, Canada. Self-management support is lacking in cancer care and little attention has been focused on the required preparation of nurses to provide self-management support and behavior change counseling. Our training program may have potential for improving nurses' provision of self-management support, however, further testing in a larger population of nurses is required to assess effects on nurses skills and its impact on patient uptake of self-management behaviors and health outcomes. 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Multiple myeloma (MM) rarely occurs in patients 40 years of age and younger. This young age has been reported to correlate with improved survival in patients with MM. The objective of this study is to describe presenting features and outcomes of patients ≤40 years of age with MM who undergo autologous stem cell transplantation (ASCT) as first-line treatment, and compare overall survival (OS) and progression free survival (PFS) to patients aged 41-65 years. We performed a retrospective institutional review of all patients ≤40 years of age and 41-65 years of age at the time of diagnosis of MM who had undergone upfront ASCT from January 1, 1990, to July 31, 2007. Thirty-eight patients ≤40 years of age and 608 patients aged 41-65 were identified. There was a high rate of plasma cell leukemia (PCL) in young patients at 11% compared to the reported rate of 2%-4%. At diagnosis, there was an increased rate of renal failure in the young cohort compared to patients aged 41-65 years at 25% versus 16% and Bence Jones proteinuria at 81% versus 51%. The rate of complete or partial response was similar between the groups at 79% and 83% in the young and older cohorts, respectively. Median PFS post-ASCT was 22.0 months (95% confidence interval [CI]: 16.1, 28.0), versus 26.9 months (95% CI: 24.0, 29.8) for patients aged 41-65 years (P = .66). Median OS from date of ASCT was also similar to those over 40 years: 68.1 months (95% CI: 39.0, 97.2) versus 80.7 months (95% CI: 68.1, 93.4); P = .90. Treatment-related mortality (TRM) was low at 2.6% and 2.3% in the young and older cohorts, respectively. Despite previous reports that young age is a positive prognostic marker, our study found OS post-ASCT is equivalent to those aged 41-65 years. This study emphasizes the importance of developing strategies to better the outcomes of young patients with MM. [Copyright &y& Elsevier]

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. [ABSTRACT FROM AUTHOR]

The article presents a study on cyclophosphamide, bortezomib and dexamethasone induction therapy for newly diagnosed patients with multiple myeloma (MM). It discusses the development of new therapies for MM, method used to calculate the patients' survival, and the overall response for all patients in the study.

High dose chemotherapy followed by autologous stem cell transplant (ASCT) is a cornerstone of frontline therapy for multiple myeloma (MM) [[1]]. Four of the ten transplants were performed as second-line therapy, including two for relapsed disease 42 and 48 months after frontline ASCT (Patients #4 and #5 on Table 1) and one relapsing 47 months after frontline syngeneic transplant (Patient #3). GVHD was questioned in 2 patients (Patients #3 and #5), both receiving allogeneic-like conditioning and cyclosporine prophylaxis. Two of nine patients developed a secondary cancer during follow up (Patient #5 myelodysplastic syndrome 7 years post-syngeneic transplant; Patient #4 transitional cell carcinoma 11 years post-syngeneic transplant). [Extracted from the article]

Summary: 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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/m2, 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The presence of certain high-risk cytogenetic abnormalities, such as translocations (4;14), (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 pre-planned 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 5-fold 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The article focuses on a research related to study of inhibitor of aurora kinase called AT9283 found in patients with refractory and relapsed multiple myeloma through clinical trials. Topics discussed include measurement of expression of Histone H3 protein by western blot analysis; occurrence of thrombocytopenia in trial patients; and association of administration of AT9283 with myelosuppression; and usage of hematopoietic growth factors to manage myelosuppression.

Post-autologous stem cell transplant (ASCT) studies have demonstrated that absolute lymphocyte count (ALC) recovery is associated with prolonged survival in some hematological malignancies. To assess whether ALC recovery has prognostic significance in patients with multiple myeloma (MM) undergoing single ASCT, we conducted a retrospective analysis of ALC at different time-points in patients with MM. In total 769 consecutive patients who underwent single ASCT from January 2000 to December 2007 were evaluated. An ALC of ≥ 1400 cells/μL at day 0, day 15 and day 90 significantly correlated with a better overall survival (OS) (median OS of 111, 90.7 and 84 months vs. 74, 70.5 and 65 months, respectively,p< 0.001 for all time-points). Multivariate analysis showed that ALC is an independent prognostic factor for OS after ASCT. In conclusion, ALC is a surrogate marker of the host immune system that correlates with better survival in patients with MM undergoing single ASCT. Immunomodulatory drugs, vaccination strategies and cellular therapies in MM should be investigated. [ABSTRACT FROM PUBLISHER]

Follicular lymphoma ( FL) in young adults ( YA, <40 years old) is uncommon, and the clinical characteristics and outcomes of this group are not well defined. We conducted a retrospective database review of 427 patients with newly diagnosed FL aged 65 years or less registered at Princess Margaret Cancer Centre between 1995 and 2010. YA ( n = 61) and those 40-65 ( n = 366) were compared with regards to clinical stage at diagnosis, FL International Prognostic Index ( FLIPI) score, and the following clinical outcomes: time to second treatment, cause-specific survival (CSS) and overall survival (OS). At diagnosis, stage and FLIPI score were similar, as were the proportion of patients requiring therapy ( YA 75% versus older adults 71%). Median follow-up was 8·1 years. Time to second therapy was similar in both age groups (5-year probability 23% YA versus 27% older adults; Gray's P-value = 0·76). Ten-year OS was significantly higher for YA (87% versus older adults 72%; P = 0·029). On multivariate analysis, age <40 years, low FLIPI score and observation as initial management were favourable prognostic factors for OS and CSS. We conclude that YA with FL have a favourable prognosis compared to older patients; whether this reflects competing mortality risks or age-related differences in lymphoma biology warrants further investigation. [ABSTRACT FROM AUTHOR]

Subcutaneous injection is now commonly used as a standard for bortezomib administration. The bortezomib (Velcade®) product monograph recommends that intravenous injections be prepared at a concentration of 1mg/mL, while sub- cutaneous injections may be prepared at a concentration of 2.5mg/mL. Many institutions and subcutaneous administration guidelines use 2mL as the maximum volume for subcutaneous injection. Using 2mL as the maximum volume for injection would mean that many patients receiving bortezomib will receive two injections during each visit with common dosing parameters. In this prospective study evaluating a change to subcutaneous administration, bortezomib 1mg/mL was administered subcutaneously at a higher maximum of 3mL per injection site. For 57 individual patients, 339 doses were administered. Skin reactions were noted in 42% with all reactions being Grade 1 or 2. Patients tolerated subcutaneous injections well and only four patients were switched back to intravenous route. This is the first time that subcutaneous bortezomib of a volume up to a maximum of 3mL (bortezomib 3mg) per injection site has been reported. This higher single dose is well tolerated with limited skin reactions, no significant hypotension and facilitates ease of administration with only 5 patients needing two injections per visit. If the maximum volume for injection was kept at 2mL, a total of 46 patients would have received two injections per visit. [ABSTRACT FROM AUTHOR]

Background: The NCIC CTG LY.12 study showed that gemcitabine, dexamethasone, and cisplatin (GDP) were noninferior to dexamethasone, cytarabine, and cisplatin (DHAP) in patients with relapsed or refractory aggressive histology lymphoma prior to autologous stem cell transplantation. We conducted an economic evaluation from the perspective of the Canadian public healthcare system based on trial data. Methods: The primary outcome was an incremental cost utility analysis comparing costs and benefits associated with GDP vs DHAP. Resource utilization data were collected from 519 Canadian patients in the trial. Costs were presented in 2012 Canadian dollars and disaggregated to highlight the major cost drivers of care. Benefit was measured as quality-adjusted life-years (QALYs) based on utilities translated from prospectively collected quality-of-life data. All statistical tests were two-sided. Results: The mean overall costs of treatment per patient in the GDP and DHAP arms were $19 961 (95% confidence interval (CI) = $17 286 to $24 565) and $34 425 (95% CI = $31 901 to $39 520), respectively, with an incremental difference in direct medical costs of $14 464 per patient in favor of GDP (P < .001). The predominant cost driver for both treatment arms was related to hospitalizations. The mean discounted quality-adjusted overall survival with GDP was 0.161 QALYs and 0.152 QALYs for DHAP (difference = 0.01 QALYs, P = .146). In probabilistic sensitivity analysis, GDP was associated with both cost savings and improved quality-adjusted outcomes compared with DHAP in 92.6% of cost-pair simulations. Conclusions: GDP was associated with both lower costs and similar quality-adjusted outcomes compared with DHAP in patients with relapsed or refractory lymphoma. Considering both costs and outcomes, GDP was the dominant therapy. [ABSTRACT FROM AUTHOR]

Rituximab is a monoclonal anti-CD20 antibody that is standard of care for treatment of B-cell non-Hodgkin lymphoma (NHL). The purpose of this study was to quantify the incidence of rituximab (R)-related interstitial pneumonitis (IP) in patients with NHL receiving immunochemotherapy. All patients with NHL who received cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP), cyclophosphamide, vincristine and prednisone (CVP), R-CHOP or R-CVP in Princess Margaret Hospital between June 1998 and August 2009 were retrospectively reviewed. We compared cohorts of patients who did and did not receive R and documented the incidence of IP during and/or post-treatment. In total 560 patients were included in this analysis. The rate of IP in the entire cohort was 2.9% (16/560) with a trend toward a higher rate in the R group (3.95% vs. 1.3% [odds ratio 3.1, 0.84-17.27, p = 0.074]). Baseline pulmonary computed tomography abnormalities in patients with lymphoma are relatively common. The addition of R to chemotherapy does not significantly increase the risk of symptomatic chemotherapy-related IP. [ABSTRACT FROM AUTHOR]

Neutropenia is a major dose-limiting toxicity associated with lenalidomide in relapsed/refractory multiple myeloma (MM). The optimal dosing schedule of granulocyte colony-stimulating factor (G-CSF) is unclear. We developed an intermittent G-CSF schedule (4-6 doses per cycle) initiated upon onset of grade 3-4 neutropenia. Of 216 patients with relapsed/refractory MM treated at our center with lenalidomide/dexamethasone on an Expanded Access Program, there was a high incidence of grade 3-4 neutropenia (61%) and grade 3-4 infections (37%). Despite intermittent G-CSF use in 117 patients, recurrent grade 3-4 neutropenia was common (59%), and dose reductions were required in 40% of G-CSF recipients, most due to thrombocytopenia. G-CSF recipients had a longer duration on therapy and achieved a higher rate and depth of response. Intermittent G-CSF may be an effective approach for lenalidomide dose-preservation, which may lead to improved outcomes, although it does not prevent infections or thrombocytopenia-related dose limitations. [ABSTRACT FROM AUTHOR]

A letter to the editor in response to the article "Lenalidomide (Revlimid), bortezomib (Velcade) and dexamethasone for the treatment of secondary plasma cell leukemia," that was published in a previous issue of the journal is presented.

This single institution, open label Phase I- II dose escalation trial evaluated the safety and efficacy of the combination of lenalidomide (Revlimid®), cyclophosphamide and prednisone ( CPR) in patients with relapsed/refractory multiple myeloma. The maximal administered dose of CPR consisted of cyclophosphamide 300 mg/m2 on day 1, 8, and 15, lenalidomide 25 mg on d 1-21 and prednisone 100 mg every other day in a 28-d cycle. Between November 2007 and June 2009, 32 patients were entered in cohorts of three at three dose levels. The median age was 64 years, 59% were male, with a median two prior regimens. Responding patients could stay on treatment until progression. The full-dose CPR regimen produced no dose-limiting toxicity and was delivered for a median of 16 months (3·5-65 months) with acceptable safety and tolerance. The overall response rate (≥ partial response) was 94% at a median follow up of 28 months. The median progression-free survival was 16·1 months [95% confidence interval ( CI); 10·9-22·5 months], while the median overall survival was 27·6 months (95% CI; 16·8-36·6 months). Only the beta-2 microglobulin level at protocol entry correlated with a better survival ( P = 0·047). These observations compare favourably with other 2- and 3- drug combinations for relapsed/refractory myeloma, and suggest that CPR should be evaluated further in the setting of relapsed/refractory disease, or in newly diagnosed patients. [ABSTRACT FROM AUTHOR]

Choosing Wisely® is a medical stewardship initiative led by the American Board of Internal Medicine Foundation in collaboration with professional medical societies in the United States. The American Society of Hematology (ASH) released its first Choosing Wisely® list in 2013. Using the same evidence-based methodology as in 2013, ASH has identified 5 additional tests and treatments that should be questioned by clinicians and patients under specific, indicated circumstances. The ASH 2014 Choosing Wisely® recommendations include: (1) do not anticoagulate for more than 3 months in patients experiencing a first venous thromboembolic event in the setting of major, transient risk factors for venous thromboembolism; (2) do not routinely transfuse for chronic anemia or uncomplicated pain crises in patients with sickle cell disease; (3) do not perform baseline or surveillance computed tomography scans in patients with asymptomatic, early-stage chronic lymphocytic leukemia; (4) do not test or treat for heparin-induced thrombocytopenia if the clinical pretest probability of heparin-induced thrombocytopenia is low; and (5) do not treat patients with immune thrombocytopenia unless they are bleeding or have very low platelet counts. [ABSTRACT FROM AUTHOR]

Follicular lymphoma (FL) is characterized by an initial response to treatment with inevitable relapse. We evaluated chemoimmunotherapy resistance (CIR resistance) including transformation. We identified patients who received rituximab combination therapy for symptomatic FL. CIR resistance was defined as disease progression during rituximab-based chemoimmunotherapy, rituximab maintenance or within 6 months of treatment completion. Our primary outcome was time to early progression (CIR resistance). Between July 2006 and April 2010, 132 patients met the inclusion criteria and 22 (16.7%) demonstrated CIR resistance with a median follow-up of 33 months. High-risk Follicular Lymphoma International Prognostic Index (FLIPI) score was predictive of CIR resistance (hazard ratio [HR] 2.43; 95% confidence interval [CI], 1.4-4.1; p = 0.001). Overall, eight patients (36.3%) transformed (biopsy-proven), with no transformation in the chemoimmunotherapy responder group. Median overall survival in the CIR resistant group was 47 months. Patients with CIR resistance had high rates of histologic transformation and shorter survival with poor response to next therapy. [ABSTRACT FROM AUTHOR]

CAN2007 was a phase 1/2 study of once- and twice-weekly single-agent bortezomib in relapsed primary systemic amyloid light chain amyloidosis (AL) amyloidosis. Seventy patients were treated, including 18 and 34 patients at the maximum planned doses on the once- and twice-weekly schedules. This prespecified final analysis provides mature response and long-term outcomes data after 3-year additional follow-up since the last report. In the once-weekly 1.6 mg/m(2) and twice-weekly 1.3 mg/m(2) bortezomib groups, final hematologic response rates were 68.8% and 66.7%; 80% of patients in each group sustained their response for ⩾1 year. One-year progression-free rates were 72.2% and 76.8%. Median overall survival (OS) was 62.1 months and not reached; 4-year OS rates were 75.0% and 63.0%. Low baseline difference in κ/λ free light-chain level was associated with higher hematologic complete response rates and longer OS. At data cutoff, 40 (57%) patients had received subsequent therapy, including 19 (27%) retreated with bortezomib, 11 (58%) of whom achieved complete or partial hematologic responses. Four patients received prolonged bortezomib for between 3.5 and 5.6 years, with no new safety concerns, highlighting the feasibility of long-term therapy. Single-agent bortezomib produced durable hematologic responses and promising long-term OS in relapsed AL amyloidosis. [ABSTRACT FROM AUTHOR]

Recently, the occurrence of oligoclonal and monoclonal bands (OB/MB) unrelated to the original clone has been reported in patients with multiple myeloma who undergo autologous stem cell transplant (ASCT) and/or receive treatment with novel agents. The aim of our study was to assess the impact of OB/MB occurrence on overall (OS) and progression-free survival (PFS) for patients with MM undergoing single ASCT at our institution. All consecutive patients with documented MM undergoing single ASCT from January 2000 to December 2012 were evaluated. Ninety-nine patients (11.8%) developed OB/MB at day 100 post-ASCT (32.3%, OB and 67.7%, MB). Multivariate analysis identified the development of OBs/MBs as an independent favorable prognostic factor for OS and PFS ( p = 0.008 and 0.012, respectively). In conclusion, the occurrence of OB/MB is an important prognostic factor in patients with MM who undergo ASCT. Its impact on clinical outcomes should be prospectively validated and its biological significance further elucidated. [ABSTRACT FROM AUTHOR]

Autologous stem-cell transplant has been widely used to treat patients with AL amyloidosis. However, transplant-related mortality rates are high, and a recent randomized trial suggested that non-transplant regimens produced comparable results with less toxicity. In order to define the role of patient selection in stem cell transplantation, we evaluated 78 consecutive AL amyloidosis patients transplanted at our centre. Transplant-related mortality occurred in 11·5%. Complete haematological response and organ response were achieved in 56% and 60%. Median overall survival was significantly lower for patients with brain-type natriuretic peptide ( BNP) >300 pg/ml (17·5 months vs. not-reached) ( P = 0·0004), troponin-I >0·07 ng/ml (13·5 months vs. not-reached) ( P = 0·00001) and those not achieving a complete haematological response (88 months vs. not-reached) ( P = 0·0345); high BNP and troponin-I were the most important predictive factors in a multivariate analysis. Based on this study, patients with BNP <300 pg/ml and/or normal levels of troponin-I should be considered transplant candidates. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Despite demonstrable risk of venous thromboembolism (VTE), thromboprophylaxis continues to be underutilized in hospitalized cancer patients. Our study evaluated institutional VTE prophylaxis rates after devising a series of strategic interventions to longitudinally improve adherence rates over a period of eight years. Methods and materials: Between 2004 and 2012, a series of interventions were implemented to improve the thromboprophylaxis rate among patients with solid tumours hospitalized at our institution using quality improvement methodology. Interventions included development of guidelines and institutional policies coupled with educational in-services for physicians, nurses and pharmacists and engagement of the Cancer Quality Committee. Thromboprophylaxis rates were monitored to assess response to interventions. Results: At the outset in 2004, 11 of 57 (19.3%) eligible patients received appropriate pharmacological prophylaxis and formed the baseline of our analysis. Post-2009 policy implementation and educational sessions, 46.5% of an eligible 185 inpatients were administered thromboprophylaxis. Following a two-year grace period to allow for policy acceptance, three audits were conducted in 2011 for which an average prophylaxis rate of 62.3% resulted. In 2012, following another round of educational sessions, a 96.7% rate was achieved and maintained ten weeks later. Minimal bleeding risk was observed during this eight year initiative. Conclusion: A reproducible 96.7% prophylaxis uptake rate was the result of our perseverance and persistence in believing that culture change was inevitable through continuously collaborating with stakeholders at all levels. [Copyright &y& Elsevier]

Choosing Wisely® is a medical stewardship and quality improvement initiative led by the American Board of Internal Medicine Foundation in collaboration with leading medical societies in the United States. The ASH is an active participant in the Choosing Wisely® project. Using an iterative process and an evidence-based method, ASH has identified 5 tests and treatments that in some circumstances are not well supported by evidence and which in certain cases involve a risk of adverse events and financial costs with low likelihood of benefit. The ASH Choosing Wisely® recommendations focus on avoiding liberal RBC transfusion, avoiding thrombophilia testing in adults in the setting of transient major thrombosis risk factors, avoiding inferior vena cava filter usage except in specified circumstances, avoiding the use of plasma or prothrombin complex concentrate in the nonemergent reversal of vitamin K antagonists, and limiting routine computed tomography surveillance after curativeintent treatment of non-Hodgkin lymphoma. We recommend that clinicians carefully consider anticipated benefits of the identified tests and treatments before performing them. [ABSTRACT FROM AUTHOR]

Involvement of the central nervous system ( CNS) in multiple myeloma ( MM) is a rare complication, with reported survival of <6 months. This report describes 37 MM patients with leptomeningeal and/or parenchymal brain involvement treated at our institution and identifies factors associated with long-term survival. From January 1999 to December 2010, 37 patients with CNS MM were evaluated at our institution. Clinical characteristics, treatment and survival were retrospectively collected. CNS disease was present at MM diagnosis in 24% and at relapse in 76%. Plasma cell leukemia (40%) and skull plasmacytomas (65%) were common, suggesting haematological and contiguous spread. Intrathecal ( IT) chemotherapy was used in 81%, cranial and/or spinal irradiation in 78%, and various systemic therapies [immunomodulatory agents ( IMiDs) (51%), cisplatin-based ( DPACE; cisplatin, doxorubicin, cyclophosphamide, etoposide) (27%), bortezomib (19%), alkylators (11%), dexamethasone alone (8%), auto-transplant (5%)]. Median survival from CNS disease was only 4·6 months [95% confidence interval ( CI): 2·8-6·7]; however, nine patients had prolonged survival (median: 17·1 months, 95% CI: 13·2-67·4). In general, these long-term survivors were treated with radiotherapy, multi-dosing IT chemotherapy, and IMi D-containing therapy. CNS MM is a highly aggressive disease but in our experience, long-term survival can be achieved with the combination of multi-dosing IT chemotherapy, radiation and IMi D-based therapy. [ABSTRACT FROM AUTHOR]

This is a randomized trial evaluating the safety and immunogenicity of one or two doses of 2009 pandemic H1N1 influenza vaccination in adults with lymphoid malignancies. Adults with a lymphoid malignancy receiving active systemic therapy, or within a year after autologous stem cell transplant, received one dose of AS03-adjuvanted A/California/7/2009 (H1N1) vaccine, and were randomized 21 days later to a second dose or no further vaccination. The primary outcomes were seroprotection and seroconversion rates by hemagglutination inhibition 21 and 42 days after initial vaccination. Twenty-two patients received one dose, and 20 patients received a second dose. Seroconversion rates at day 21 were 30% (one dose) and 5% (two doses), and subsequently 30% for both groups at day 42. Seroprotection rates at day 21 were 40% (one dose) and 15% (two doses), and subsequently 35% (one dose) and 40% (two doses) at day 42. Differences in serologic endpoints were not statistically significant between both study arms at day 42. Patients with low levels of B-cells (CD19-positive) had low seroconversion rates on days 21 (odds ratio [OR] 0.74, 95% confidence interval [CI] 0.59-0.93, p = 0.043) and 42 (OR 0.12, 95% CI 0.01-1.07, p = 0.058). Only three of the 14 patients who received rituximab achieved seroprotective titers by day 42. Patients with lymphoid malignancies did not achieve rates of seroconversion or seroprotection seen in healthy subjects despite a second dose and the use of an adjuvant. Notwithstanding suboptimal immunogenicity, seasonal and pandemic influenza vaccination should continue to be recommended. [ABSTRACT FROM AUTHOR]

Dexamethasone ± thalidomide with infusion of cisplatin, doxorubicin, cyclophosphamide, and etoposide [D(T) PACE] is generally reserved as salvage therapy for aggressive multiple myeloma ( MM) or plasma cell leukaemia ( PCL) resistant to conventional therapies. The efficacy and durability of this potentially toxic regimen in this setting is unclear. We identified 75 patients who received D(T) PACE for relapsed/refractory MM at two tertiary care centres: Princess Margaret Hospital, Toronto and Mayo Clinic Arizona. At time of D(T) PACE, 16 patients had PCL and three patients had leptomeningeal disease. Patients were heavily pretreated (median three prior regimens, range 1-12; prior autologous stem cell transplant [ ASCT] 33%). Overall response rate was 49% (very-good partial response 16%, partial response 33%) with stable disease in an additional 36%. Median progression-free survival ( PFS) was 5·5 months (95% confidence interval [ CI]:4·3-9·8); overall survival ( OS) 14·0 months (95% CI:8·7-19·3). Thirty-five patients proceeded to ASCT or clinical trial, with median PFS for this subset of 13·4 months (95% CI:7·7-20·1) and OS 20·5 months (95% CI:14·8-63·8). D(T) PACE is an effective salvage therapy for heavily pretreated MM patients. Although the overall response rate of 49% in this poor prognosis cohort is reasonable, the PFS is short, suggesting the best role for D(T) PACE is in bridging to definitive therapy, such as transplantation. [ABSTRACT FROM AUTHOR]

The combination of lenalidomide, bortezomib and dexamethasone (RVD) has shown excellent efficacy in patients with relapsed or refractory multiple myeloma (RRMM). The aim of our study was to assess the efficacy and toxicity profile of RVD for patients with advanced RRMM. We retrospectively reviewed the records of all patients with RRMM treated with RVD between March 2009 and December 2011. Thirty patients received ≥1 full cycle of RVD. Primary endpoints were overall response rate (ORR), progression-free survival (PFS) and overall survival (OS). After a median of 5 cycles (1-16), a very good partial response (VGPR) was seen in 10%, partial response (PR) in 36.7% and stable disease (SD) in 13.3% (ORR of 46.7%). Disease progression occurred in 21 patients at a median of 3 months (range 1.41-4.59). Eight patients (26%) experienced grade 3/4 adverse events, including anemia, neutropenia, muscle weakness and pneumonia. No patient experienced worsening peripheral neuropathy. Although RVD has been previously shown to be effective in RRMM, the ORR and PFS we observed were affected by very advanced disease status and heavy prior exposure to novel agents. Nevertheless, six of these patients with RRMM experienced a benefit of ≥6 months, suggesting synergism of this immunomodulatory derivative/proteasome inhibitor combination and/or re-establishment of drug sensitivity by an emergent myeloma clone. [ABSTRACT FROM AUTHOR]

Mantle-cell lymphoma (MCL) is a rare cancer, with the majority of patients (pts) presenting in stage Ill-IV and the outcomes are poor. To determine the curability of localized MCL, we examine stage I-II pts at our institution between 1990-2007.26 pts with stage I (38%) and stage II (62%) were referred. Sites involved were head and neck in 73%. Five had a blastoid variant. Five patients were treated with palliative intent. Analysis was focused on pts treated with a curative intent (21 pts): 17 CT-I- RT, 2 RT, 2 CT followed by ASCT. 13 patients received CHOP, 5-RCHOP, 1-CVP; most received ≤ 6 cycles.The RT median dose was 35Gy and IFRT for the majority. For 21 pts treated with a curative intent, median follow up was 5.8 years. The overall response rate was 95%. Among the 19 CR/CRu pts, 9 relapsed for a 5-year relapse rate of 46%. Relapses were mainly observed at distant sites, 3 were in GI tract, 1 had both local and distant relapse. Median PFS and OS were 3.2 and 6.4years, respectively. 5-year OS was 62%. In univariate analysis, blastoid variant and stage II were prognostic factors for PFS. Multivariate analysis could not be performed due to the small sample size. With a treatment approach using combined CT+RT for stage I-II MCL, local control was achieved in 94%. Systemic relapse remains a significant problem, especially for stage II and blastoid variant. Radiotherapy should remain part of curative treatment plan in stage I-II MCL. [ABSTRACT FROM AUTHOR]

Carfilzomib is a next-generation, selec-tive proteasome inhibitor being evaluated for the treatment of relapsed and refrac-tory multiple myeloma. In this open-label, single-arm phase 2 study (PX-171-003-A1), patients received single-agent carfil-zomib 20 mg/m2 intravenously twice weekly for 3 of 4 weeks in cycle 1, then 27 mg/m² for ≤12 cycles. The primary endpoint was overall response rate (> partial response). Secondary end-points included clinical benefit response rate (> minimal response), duration of response, progression-free survival, over-all survival, and safety. A total of 266 patients were evaluable for safety, 257 for efficacy; 95% were refractory to their last therapy; 80% were refractory or intolerant to both bortezomib and lena-lidomide. Patients had median of 5 prior lines of therapy, including bortezomib, lenalidomide, and thalidomide. Overall re-sponse rate was 23.7% with median dura-tion of response of 7.8 months. Median overall survival was 15.6 months. Ad-verse events (AEs) were manageable with- out cumulative toxicities. Common AEs were fatigue (49%), anemia (46%), nausea (45%), and thrombocytopenia (39%). Thirty-three patients (12.4%) experienced periph-eral neuropathy, primarily grades 1 or 2. Thirty-three patients (12.4%) withdrew be-cause of an AE. Durable responses and an acceptable tolerability profile in this heavily pretreated population demonstrate the po-tential of carfilzomib to offer meaningful clinical benefit. This trial was registered at www.clinicaltrials.gov as #NCT00511238. [ABSTRACT FROM AUTHOR]

The article focuses on the study of single-agent carfilzomib in bortezomib-naive patients with multiple myeloma. It mentions that clinical activity of bortezomib in malignancies has resulted in further interest in the proteasome as a target in a broad range of cancers. It states that carfilzomib is a selective proteasome inhibitor that binds irreversibly to its target and has shown promising response in the phase one clinical trial and elicits a low incidence of peripheral neuropathy.

The role of a second autologous stem cell transplant (ASCT) as salvage therapy is unclear, particularly with the availability of novel agents to treat progressive multiple myeloma (MM). We retrospectively reviewed all MM patients who received a second ASCT as salvage therapy at our center from March 1992 to December 2009. Eighty-one MM patients received a second ASCT for relapsed MM. The median time to relapse after first transplant was 39 months (9.83-100). All patients received reinduction therapy before the second ASCT. The high-dose regimen given before the second ASCT consisted of melphalan (MEL) alone in the majority. Complete response, very good partial response, and partial response were seen in 7.7%, 39.7%, and 50%, respectively, at day 100 post-ASCT; the median time to relapse after the second ASCT was 19 months. Early deaths occurred in 2.6%. Median progression-free survival (PFS) based on the time to myeloma relapse after first ASCT was 9.83 months (relapse ≤24 months) and 17.3 months (relapse ≥24 months) (P < .05). Median overall survival (OS) was 28.47 months (relapse ≤24 months) and 71.3 months (relapse >24 months) (P = .006). Second ASCT is a feasible and safe option for salvage therapy in MM. The best outcome was observed in patients whose time to progression was >24 months after first ASCT, as these patients had a subsequent PFS lasting over 1 year and an OS of almost 6 years. [Copyright &y& Elsevier]