Tandem Autologous Stem Cell Transplantation Does Not Benefit High-Risk Myeloma Patients in the Maintenance Era: Real-World Results from The Canadian Myeloma Research Group Database.

In patients with multiple myeloma (MM), the presence of high-risk cytogenetic abnormalities is associated with worse disease control and survival. Autologous stem cell transplant (ASCT) does benefit these patients. Tandem transplantation has been explored as a means to deepen responses and further improve survival however, its role remains controversial. This is particularly true in the era of novel agent induction and post-transplant maintenance therapy. The aim of this study was to use the Canadian Myeloma Research Group database and examine a large cohort of real-world patients comparing the outcomes of tandem versus single ASCT specifically in high-risk patients receiving novel agent-based induction and post-transplant maintenance. The data for this study was derived retrospectively from a comprehensive national-level database of Canadian patients with MM. High-risk cytogenetics was defined as presence of del17p, t(4;14), or t(14;16). Those receiving allogeneic transplant were excluded. Tandem transplantation was defined as a second ASCT performed consecutively without interim relapse or progression after first ASCT. Those with relapse or progressive disease within 3 months of completing a first transplant were excluded. We compared response depth, progression-free, and overall survival (OS) based on single or tandem transplantation procedures. The impact of covariates of interest was also assessed. A total of 381 patients with high-risk cytogenetics were identified. A total of 242 received single and 139 patients received tandem transplants. All received post-transplant maintenance. The most common induction regimen for these patients was cyclophosphamide, bortezomib, and steroids (CyBorD, 87%). Forty-one patients (10.8%) required reinduction prior to first ASCT. The best overall responses at any time were 98.3% (90.5% ≥ very good partial response [VGPR]) and 98.6% (89.9% ≥ VGPR) in the single and tandem ASCT groups, respectively. Survival outcomes were similar with the median progression-free survival for single or tandem ASCT of 35.2 and 35.3 months (P = .88) and the median OS were 92.6 and 88.9 months, respectively (P = .72). No statistically significant differences were seen based on type of cytogenetic abnormality or type of maintenance. This was confirmed on multivariate analysis. In the real-world setting, tandem ASCT does not improve outcomes for MM patients with high-risk cytogenetics. This may be driven by the use of effective pre- and post-ASCT therapies. The development of more potent induction and consolidation along with current nearly ubiquitous continuous maintenance therapies until disease progression does not support the use of a second high-dose procedure.

Long-term follow-up of outcomes including progression-free survival 2 in patients with transplant-ineligible multiple myeloma in the real-world practice: A multi-institutional report from the Canadian Myeloma Research Group (CMRG) database.

Multiple myeloma remains an incurable cancer mostly affecting older adults and is characterized by a series of remission inductions and relapses. This study aims to evaluate the outcomes in newly diagnosed transplant-ineligible patients using bortezomib/lenalidomide-based regimens in the Canadian real world as well as their outcomes in the second line. The Canadian Myeloma Research Group Database (CMRG-DB) is a national database with input from multiple Canadian Centres with now up to 8000 patients entered. A total of 1980 transplant ineligible patients were identified in the CMRG-DB between the years of 2007-2021. The four most commonly used induction regimens are bortezomib/melphalan/prednisone (VMP) (23%), cyclophosphamide/bortezomib/dexamethasone (CyBorD) (47%), lenalidomide/dexamethasone (Rd) (24%), and bortezomib/lenalidomide/dexamethasone (VRd) (6%). After a median follow-up of 30.46 months (0.89-168.42), the median progression-free survival (mPFS) and median overall survival (mOS) of each cohort are 23.5, 22.9, 34.0 months, and not reached (NR) and 64.1, 51.1, 61.5 months, and NR respectively. At the time of data cut-off, 1128 patients had gone on to second-line therapy. The mPFS2 based on first-line therapy, VMP, CyBorD, Rd, and VRd is 53.3, 48.4, 62.7 months, and NR respectively. The most common second-line regimens are Rd (47.4%), DRd (12.9%), CyBorD (10.3%), and RVd (8.9%) with a mPFS and a mOS of 17.0, 31.1, 15.4, and 14.0 months and 34.7, NR, 47.6, 33.4 months, respectively. This study represents the real-world outcomes in newly diagnosed transplant-ineligible myeloma patients in Canada. The spectra of therapy presented here reflect the regimens still widely used around the world. While this is sure to change with anti-CD38 monoclonal antibodies now reflecting a new standard of care in frontline therapy, this cohort is reflective of the type of multiple myeloma patient currently experiencing relapse in the real-world setting.

The EASEMENT study: A multicentre, observational, cross-sectional study to evaluate patient preferences, treatment satisfaction, quality of life, and healthcare resource use in patients with multiple myeloma receiving injectable-containing or fully oral therapies.

OBJECTIVE: As multiple myeloma (MM) therapies advance, understanding patients', caregivers', and physicians' perspectives on, and satisfaction with, available treatment options and their impact on quality of life (QoL), is important. METHODS: EASEMENT is a real-world, observational, cross-sectional study conducted in 19 sites within the UK, Canada, and Italy using retrospective chart reviews and surveys. Enrolled patients had clinical history available since diagnosis and had received ≥1 cycle of their current line of therapy. Primary objectives were to describe patient/caregiver QoL (EQ-5D-5L questionnaire), patient preference for oral/injectable therapies (single discrete-choice question), and patient satisfaction (TSQM-9 questionnaire). RESULTS: Between October 2018 and March 2020, 399 patients were enrolled (n = 192 newly diagnosed multiple myeloma [NDMM], n = 206 relapsed/refractory multiple myeloma [RRMM], n = 1 missing). Among NDMM and RRMM patients, 78%/22% and 42%/58% were receiving injectables/orals, respectively. Both NDMM and RRMM patients significantly preferred orals versus injectables (p < .0001). No significant differences were reported in treatment satisfaction or QoL, but treatment convenience favoured orals over injectables with near significance (p = .053). CONCLUSION: MM patients perceived greater convenience and preference for orals versus injectables. Oral treatments are useful for patients who cannot or prefer not to travel to clinics, or cannot perform self-injection within the community.

Belantamab mafodotin, pomalidomide and dexamethasone in refractory multiple myeloma: a phase 1/2 trial.

Due to evolving treatment standards for newly diagnosed multiple myeloma, many patients will be triple-class exposed after initial relapses and have poor survival. Novel therapies and combinations are therefore required to improve outcomes. B cell maturation antigen (BCMA)-targeted biologics have emerged as an important new area of therapeutics for relapsed multiple myeloma. The two-part ALGONQUIN trial evaluated various doses and schedules of the anti-BCMA antibody-drug conjugate belantamab mafodotin plus pomalidomide and dexamethasone for patients who are lenalidomide refractory and proteosome inhibitor exposed. The primary endpoints, including evaluating dose-limiting toxicities, establishing the recommended Part 2 dose (RP2D) and overall response rate for patients treated at the RP2D, were met. Secondary efficacy endpoints included progression-free survival and overall survival. Patients treated on study (N = 87) had a median of three previous regimens and 55.2% were triple-class refractory. At the RP2D the most common adverse events were decrease in best-corrected visual acuity (71.1%), keratopathy (65.8%), fatigue (57.9%), infection (47.4%; 7.9% grade ≥3), neutropenia (39.5%) and thrombocytopenia (39.5%). For RP2D patients (n = 38), the overall response rate was 85.3%, ≥very good partial response 75.7% and estimated two-year progression-free survival 52.8% (95% confidence interval, 33.9% to 82.4%), at a median follow-up of 13.9 months. The RP2D schedule was associated with manageable antibody-drug conjugate-associated corneal adverse events and improved tolerability without compromising efficacy. Belantamab mafodotin plus pomalidomide and dexamethasone induced durable responses with promising overall survival in relapsed multiple myeloma, the results of which are yet to be confirmed in the phase 3 DREAMM-8 study. ClinicalTrials.gov Identifier: NCT03715478 .