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The phase 3 FIRST trial demonstrated significant improvement in progression‐free survival (PFS) and overall survival (OS) with an immune‐stimulatory agent, lenalidomide, in combination with low‐dose dexamethasone until disease progression (Rd continuous) vs melphalan +prednisone + thalidomide (MPT) in transplant‐ineligible patients with newly diagnosed multiple myeloma (NDMM). Rd continuous similarly extended PFS vs fixed‐duration Rd for 18 cycles (Rd18). Outcomes in the Canadian/US subgroup (104 patients per arm) are reported in this analysis. Rd continuous demonstrated a significant improvement in PFS vs MPT (median, 29.3 vs 20.2 months; HR, 0.69 [95% CI, 0.49‐0.97]; p = 0.03326) and an improvement vs Rd18 (median, 21.9 months). Median OS was 56.9 vs 46.8 months with Rd continuous vs MPT (p = 0.15346) and 59.5 months with Rd18. The overall response rate was higher with Rd continuous and Rd18 (78.8% and 79.8%) vs MPT (65.4%). In the 49.0%, 52.9%, and 29.8% of patients with at least very good partial response in the Rd continuous, Rd18, and MPT arms, respectively, the median PFS was 56.0, 30.9, and 40.2 months, respectively. The most common grade 3/4 treatment‐emergent adverse events were neutropenia (28.4%, 30.1%, and 52.0%), anemia (23.5%, 21.4%, and 23.5%), and infections (37.3%, 30.1%, and 24.5%) with Rd continuous, Rd18, and MPT, respectively. These results were consistent with those in the intent‐to‐treat population, confirming the benefit of Rd continuous vs MPT in the Canadian/US subgroup and supporting the role of Rd continuous as a standard of care for transplant‐ineligible patients with NDMM. [ABSTRACT FROM AUTHOR]

Chronic lymphocytic leukemia (cll) is the most common adult leukemia in North America. In 2018, the first unified national guideline in Canada was developed for the front-line treatment of cll that helped guide treatment across the country. As an update in 2022, a group of clinical experts from across Canada came together to provide input and guidance that included new and innovative treatments and approaches that will continue to provide health care professionals with clear guidance on the first-line management of cll. Recommendations were provided in consensus based on available evidence for the first-line treatment of cll. • Pre-treatment considerations as recommended include IGHV, p53 and Del17p testing. • Watch & Wait is recommended for early stage asymptomatic CLL patients. • Recommendation for patients with TP53 aberrations include BTKi or Ven+O. • Treatment for young/fit patients (no mut del(17p), TP53) includes FCR, BTKi, Ven+O. • Treatment for older or comorbid patients is complex and includes Ven+O, BTKi, chemo. [ABSTRACT FROM AUTHOR]

Following the recent publication of Canadian evidence-based guidelines for frontline treatment of chronic lymphocytic leukemia (CLL), the same group of clinicians developed guidelines for CLL in the relapsed/refractory (R/R) setting. The treatment of R/R CLL has changed significantly in the past few years, with many novel therapeutics available to hematologists across the country. These guidelines aim to standardize the management of CLL in the relapsed/refractory setting, using the best evidence currently available., Competing Interests: Declaration of Competing Interest The following represents disclosure information from the authors within the last two years related to the subject matter of this guideline: CO (Honoraria from AbbVie, AstraZeneca, Janssen, BeiGene, Roche), AA (AbbVie, AstraZeneca, Janssen (accepted into a separate account within the Ottawa Hospital Research Institute, for research/academic use only)), SR (AbbVie, AstraZeneca, BeiGene, Janssen, Roche), ASG (Research funding and honoraria from Roche, AstraZeneca, AbbVie, Janssen and honoraria from BeiGene), VB (Advisory boards for AbbVie, AstraZeneca, BeiGene, Janssen; Research Grants: CIHR, LLSC, CCMF, LC.), CC (Janssen, AstraZeneca, BeiGene, AbbVie, BMS), and NJ (AbbVie, AstraZeneca, Janssen, BeiGene, Roche, Merck., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Waldenström macroglobulinemia (WM) is a slowly progressing B-cell non-Hodgkin lymphoma characterized by monoclonal IgM gammopathy in the blood and infiltration of the bone marrow by clonal lymphoplasmacytic cells. As an incurable disease, the goals for therapy for WM are to relieve symptoms, slow disease progression, prevent organ damage, and maintain quality of life. However, given the rarity of WM, clinical trials comparing treatments for WM are limited and there is no definitive standard of care. The selection of first-line WM therapy is thus based on patient factors, disease characteristics, and drug access, with bendamustine-rituximab and Bruton's tyrosine kinase (BTK) inhibitor therapy considered preferred treatments. Other treatments such as proteasome inhibitor- or purine analogue-based therapy, alternative chemoimmunotherapy, and autologous stem cell transplantation are generally reserved for the relapsed setting but may be used in rare circumstances in earlier lines of therapy. This paper summarizes the efficacy and safety of these WM therapies and discusses considerations for treatment from a Canadian perspective., Competing Interests: R.K. has received honoraria from Janssen, BMS, Beigene, Sanofi, FORUS. N.F. has received honoraria from Pfizer and AstraZeneca; served in a consulting or advisory role for AbbVie, AstraZeneca, Beigene, Celgene/Bristol Meyers Squibb, IMV, Janssen, Kite/Gilead, Novartis, Pfizer, Roche, Seattle Genetics, and Servier; received research funding from ADC Therapeutics, AstraZeneca, Astellas, IMV, Merk, MorphoSys, and Seattle Genetics. L.H.S. has received honoraria from Amgen, Apobiologix, AbbVie, Celgene, Gilead Sciences, Janssen-Ortho, Karyopharm Therapeutics, Kite, a Gilead company, Lundbeck, Merck, Roche/Genentech, Seattle Genetics, Takeda, Teva, TG Therapeutics, AstraZeneca, Acerta Pharma, Morphosys, Incyte, Debiopharm Group, Sandoz-Novartis, Verastem, and Genmab; served in a consulting or advisory role for Celgene, AbbVie, Seattle Genetics, TG Therapeutics, Janssen, Amgen, Roche/Genentech, Gilead Sciences, Lundbeck, Amgen, apobiologix, Karyopharm Therapeutics, Kite, a Gilead company, Merck, Takeda, Teva, TG therapeutics, AstraZeneca, Acerta Pharma, MorphoSys, Incyte, Debiopharm Group, Sandoz-Novartis, Genmab, and Verastem; and received institutional research funding from Roche Genentech and Teva. M.S. has received honoraria from AstraZeneca, BeiGene, Janssen; and has participated in research trials with AstraZeneca. S.D. has received funding from BeiGene Inc. for medical writing services. C.I.C. has received research funding from Bristol Meyers Squibb and Gilead; and has served in a consulting or advisory role for Abbvie, BeiGene, Bristol Meyers Squibb, Gilead, and Novartis.

Purpose: To evaluate the efficacy and toxicity of single-agent bortezomib in Waldenström's macroglobulinemia (WM)., Patients and Methods: Symptomatic WM patients, untreated or previously treated, received bortezomib 1.3 mg/m2 intravenously days 1, 4, 8, and 11 on a 21-day cycle until two cycles past complete response (CR), stable disease (SD) attained, progression (PD), or unacceptable toxicity. Responses were based on both paraprotein levels and bidimensional disease measurements., Results: Twenty-seven patients were enrolled. A median of six cycles (range, two to 39) of bortezomib were administered. Twenty-one patients had a decrease in immunoglobulin M (IgM) of at least 25%, with 12 patients (44%) reaching at least 50% IgM reduction. Using both IgM and bidimensional criteria, responses included seven partial responses (PRs; 26%), 19 SDs (70%), and one PD (4%). Total response rate was 26%. IgM reductions were prompt, with nodal responses lagging. Hemoglobin levels increased by at least 10 g/L in 18 patients (66%). Most nonhematologic toxicities were grade 1 to 2, but 20 patients (74%) developed new or worsening peripheral neuropathy (five patients with grade 3, no grade 4), a common cause for dose reduction. Onset of neuropathy was within two to four cycles and reversible in the majority. Hematologic toxicities included grade 3 to 4 thrombocytopenia in eight patients (29.6%) and neutropenia in five (19%). Toxicity led to treatment discontinuation in 12 patients (44%), most commonly because of neuropathy., Conclusion: Bortezomib has efficacy in WM, but neurotoxicity can be dose limiting. The slower response in nodal disease may require prolonged therapy, perhaps with a less intensive dosing schedule to avoid early discontinuation because of toxicity. Future studies of bortezomib in combination with other agents are warranted.