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.

Immune response to COVID-19 vaccine is diminished in patients with hematologic malignancy. There is limited data regarding response to vaccine doses in these patients. To quantify the humoral immune response engendered by 4th and subsequent doses of SARS-CoV-2 vaccination as measured by anti-Spike (anti-S) antibody levels, based on dried blood spot (DBS) testing, in patients with hematologic malignancies. Anti-S binds to the spike protein of the SARS-CoV-2 virus and is indicative of vaccine immunogenicity. We conducted a prospective study of hematologic malignancies between August 2021 and January 2023 at 12 sites across Canada. Participants were followed longitudinally and submitted finger-prick DBS cards at set intervals associated with vaccination. Samples were processed via high throughput ELISA assay to detect serum antibodies against nucleocapsid (N) and spike (S) proteins. We obtained 3071 samples on 790 unique patients. Of these, 372 unique participants with 1840 samples had anti-S results available post-4th, 5th or 6th COVID-19 vaccine dose and were included for analysis. Three hundred thirty-three patients of the 372 participants submitted a DBS sample post 4th dose. Of these, 257 patients (77.2%) had a positive anti-S antibody. A total of 198 patients had paired samples pre- and post-dose 4, of which 59 (29.7%) had a negative anti-S antibody pre-dose 4. Of these, 20 (33.4%) developed positive anti-S antibody post-dose 4. One hundred forty-nine patients submitted a DBS sample post-dose 5. Of these, 135 patients (90.6%) had positive anti-S antibody. A total of 52 had paired samples pre- and post-dose 5. Six (8.7%) had a negative anti-S antibody pre-dose 5, of which two (33.3%) developed positive anti-S antibody post-dose 5. Of these 372 patients, 123 (34%) reported COVID-19 infection and 4 (1%) had a COVID-19 related hospitalization. There were no reported deaths from COVID-19. This prospective cohort study showed that humoral immune response improved with subsequent doses of COVID-19 vaccines.

Multiple myeloma (MM) is an incurable plasma cell malignancy. In the context of the current standard of care therapies in Canada, outcomes among patients with relapsed/refractory multiple myeloma (RRMM), particularly those with triple-class (or more) refractory disease remain poor. Immunotherapies have significantly changed the treatment landscape of MM. Since 2021, two BCMA-targeting CAR T-cell therapy products have been approved for RRMM—namely Idecabtagene vicleucel (Ide-cel) (ABECMA^®) and Ciltacabtagene autoleucel (Cilta-cel) (CARVYKTI^®), both of which are available in the US and Europe. Although they have shown unprecedented efficacy in RRMM, their clinical and logistical limitations must be acknowledged. MM CAR T-cell therapy is likely to be approved in Canada soon. Therefore, it is timely that we review the latest evidence for commercially available CAR T-cell therapy in multiple myeloma, with a focus on its relevance and impact in the Canadian setting. There will be challenges to access and strategies must be in place to ensure equitable care for all Canadians with MM. Alongside haematologists working in the immune effector cell therapy programs, providers in the community will also play a role in the ongoing monitoring and management of long-term side effects including opportunistic infections and late neurotoxicity.

Bispecific antibodies have revolutionized the treatment of multiple myeloma; however, primary treatment failure occurs in 30% to 40% of patients. In this study, we analyzed correlates of response to teclistamab and strategies to overcome primary resistance. Across two independent cohorts (n = 90), we developed the high risk of primary resistance (Hi-MM) variable, defined by extramedullary disease, plasma cell leukemia, bone marrow plasmacytosis ≥50%, or transfusion within 30 days, as a composite correlate of nonresponse. Patients without Hi-MM had overall response rates of 84% to 96% (vs. 20%–40% with Hi-MM) and significantly superior progression-free survival (P < 0.001) and overall survival (P < 0.001). Debulking chemotherapy was utilized in 19 patients; 79% then responded to teclistamab, including 100% who no longer had Hi-MM. All four patients who were primary refractory to a BCMA bispecific immediately prior to debulking then achieved deep responses to teclistamab. In conclusion, simple clinical parameters correlate with response to teclistamab, whereas debulking chemotherapy can overcome Hi-MM and successfully bridge patients to teclistamab or salvage nonresponders. Significance: A clinically assessable composite variable, Hi-MM, identifies patients who may benefit from debulking chemotherapy prior to teclistamab. By treating patients at a time of low disease burden or using debulking chemotherapy for those with a high risk of resistance, nearly all patients can benefit from the deep and durable remissions induced by teclistamab.