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.

BACKGROUND: In patients with multiple myeloma, the presence of high-risk cytogenetic abnormalities is associated with worse disease control and survival. Autologous stem cell transplant 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. OBJECTIVES: The aim of this study was to use the Canadian Myeloma Research Group database (CMRG-DB) 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. STUDY DESIGN: The data for this study was derived retrospectively from a comprehensive national-level database of Canadian patients with multiple myeloma. High-risk cytogenetics were 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 three months of completing a first transplant were excluded. We compared response depth, progression free and overall survival based on single or tandem transplantation procedures. The impact of covariates of interest was also assessed. RESULTS: 381 patients with high-risk cytogenetics were identified. 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% ≥ VGPR) and 98.6% (89.9% ≥ VGPR) in the single and tandem ASCT groups respectively. Survival outcomes were similar with the median PFS for single or tandem ASCT of 35.2 and 35.3 months (p=0.88) and the median OS were 92.6 and 88.9 months respectively (p=0.72). No statistically significant differences were seen based on type of cytogenetic abnormality or type of maintenance. This was confirmed on multivariate analysis. CONCLUSION: 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 .

Real-world results of autologous stem cell transplantation in newly diagnosed multiple myeloma: a report from the Canadian Myeloma Research Group database.

Autologous stem cell transplant (ASCT) remains an important option for eligible multiple myeloma (MM) patients as part of initial therapy. Using the Canadian Myeloma Research Group (CMRG) national database, we examined the details and outcomes of ASCT performed as first-line therapy in eligible Canadian MM patients between 2007 to 2021. We included 3821 patients with 72% receiving CyBorD induction and 2061 patients receiving maintenance, consisting of lenalidomide +/- steroids in 78.3%. The median PFS and OS for patients given a single ASCT were 35.4 and 126 months. Those receiving a second induction regimen had significantly inferior outcomes, although when maintenance was used, results were comparable regardless of the number of induction regimens administered (median PFS 55.3 vs 51.1 months [p = 0.11]; median OS 158.6 vs not yet reached [p = 0.13]). Consolidation patients had a longer median PFS (55.3 vs 34.4 months [p = 0.001]), but no significant gain in median OS (p = 0.065). Patients who received lenalidomide-based maintenance experienced a median PFS of 53.7 months and OS of 159 months. In the multivariable analysis, use of any type of maintenance therapy vs no maintenance was associated with a lower risk of progression (HR 0.52 (95% CI 0.47-0.57)) and death (HR 0.58 (95% CI 0.51-0.67)). This real-world study demonstrates that, overall, first-line treatment sequence in transplant-eligible patients produces a median OS of ≥10 years. It also highlights the contribution of post-ASCT maintenance, particularly lenalidomide given until progression.

Acquired haemophilia A: A 15-year population-based review of incidence rate, patient demographics and treatment outcomes.

INTRODUCTION: Acquired haemophilia A (AHA) is a rare bleeding disorder characterized by autoantibodies against coagulation factor VIII (FVIII). Estimates of AHA incidence are largely based on registry data, which may be prone to referral bias. Population-based studies can enhance our understanding of the epidemiology, presentation and outcomes of AHA. METHODS: We conducted a retrospective, population-based cohort study of all AHA diagnosed and treated in Manitoba, Canada over a 15-year period. Using records from the sole provincial reference laboratory, we identified all patients with FVIII inhibitors who did not have congenital haemophilia.  Using a piloted case report form, patient data was ascertained from hospital and bleeding disorder clinic records. RESULTS: From 2006 to 2021, we identified 34 patients with AHA, corresponding to a population-based incidence rate of AHA of 1.78 cases per million per year. The median age at presentation was 76 years and most cases were idiopathic (79%). Almost all patients (97%) presented with bleeding, of which 58% were considered major bleeds and required haemostatic agents in 67%. Longstanding unexplained bleeding symptoms were commonly reported, suggesting delayed diagnosis. Immunosuppressive therapy (IST) was administered in 88% of patients. Remission was achieved in 79% of patients; median time to remission was 2.1 months. There were two deaths due to bleeding. No deaths due to IST were reported. CONCLUSION: The population-based incidence of AHA in Manitoba is 1.78 cases/million/year. Bleeding is common and can be life-threatening. AHA outcomes are encouraging with the use of haemostatic agents and IST. Serious treatment-associated morbidity and mortality is uncommon.

Outcome of carfilzomib/pomalidomide-based regimens after daratumumab-based treatment in relapsed multiple myeloma: A Canadian Myeloma Research Group Database analysis.

INTRODUCTION: Although daratumumab-containing regimens improve multiple myeloma (MM) outcomes, recurrence is inevitable. METHODS AND OBJECTIVE: We performed a retrospective study using the Canadian Myeloma Research Group Database to benchmark the efficacy of carfilzomib- or pomalidomide-based therapies immediately following progression on daratumumab treatment. RESULTS: We identified 178 such patients; median number of prior lines of therapy was 3, 97% triple-class exposed, and 60% triple-class refractory. In our cohort, 75 received a subsequent carfilzomib-based therapy, 79 received a pomalidomide-based therapy, and 24 received a treatment with both immunomodulatory drug (IMiD) and proteasome inhibitor (PI) using carfilzomib and/or pomalidomide. The median progression-free survival (PFS) and overall survival (OS) for the entire cohort were 4.5 and 14.2 months, respectively. Carfilzomib-based therapy yielded a median PFS and OS of 4.5 and 10.2 months, respectively, compared to 5.2 and 21.7 months for pomalidomide-based therapy. Patients who received both IMiD and PI with carfilzomib and/or pomalidomide had a median PFS and OS of 4.1 and 14.5 months, respectively. CONCLUSION: Our observations demonstrate the poor outcome of MM patients when standard regimens based on carfilzomib and/or pomalidomide are utilized directly after daratumumab-based therapy given in the relapsed setting. Novel therapies, including immune therapies, are urgently needed to improve the outcomes of these daratumumab-exposed patients.

Redefining attrition in multiple myeloma (MM): a Canadian Myeloma Research Group (CMRG) analysis.

While most patients diagnosed with multiple myeloma (MM) receive initial therapy, reported attrition rates are high. Understanding attrition rates and characteristics of patients not receiving subsequent therapy is useful for MM stakeholders. We performed an analysis of attrition rates in a large disease-specific database of patients with newly diagnosed MM who received at least one line of therapy between Jan 1/10-Dec 31/20. Attrition was defined as failure to receive a subsequent line of therapy despite progression of MM or due to death. A total of 5548 patients were identified, 3111 autologous stem cell transplant (ASCT) patients and 2437 non-ASCT. In the ASCT cohort, the attrition rate was 7% after line 1, 12% after line 2, and 23% after line 3. In non-ASCT patients, the attrition rate was 19% after line 1, 26% after line 2, and 40% after line 3. Death was the dominant contributor to attrition across all cohorts, with a minority of patients alive with progressive disease in the absence of further therapy at each line. Multivariable analysis identified older age, shorter time to progression, and inferior response as independent risk factors for attrition. Our data show that attrition rates increase with each line of therapy and are higher in non-ASCT patients but are appreciably lower than previously reported. This study supports a revision of the previous definition of attrition, demonstrating that most patients who do not receive subsequent therapy are either continuing their current therapy and/or are in remission off-treatment rather than being irreversibly lost to attrition.

Selinexor-Based Triplet Regimens in Patients With Multiple Myeloma Previously Treated With Anti-CD38 Monoclonal Antibodies.

BACKGROUND: The increasing use of anti-CD38 monoclonal antibodies (αCD38 mAbs) for newly diagnosed or early relapsed multiple myeloma (MM), especially in non-transplant eligible patients, may lead to more patients developing αCD38 mAb-refractory disease earlier in the treatment course with fewer treatment options. PATIENTS AND METHODS: We analyzed the efficacy and safety of selinexor-based triplets (selinexor+dexamethasone [Sd] plus pomalidomide [SPd, n = 23], bortezomib [SVd, n = 16] or carfilzomib (SKd, n = 23]) in a subset of STOMP (NCT02343042) and BOSTON (NCT03110562) study patients treated previously with αCD38 mAbs. RESULTS: Sixty-two patients (median 4 prior therapies, range 1 to 11, 90.3% refractory to αCD38 mAb) were included. Overall response rates (ORR) in the SPd, SVd and SKd cohorts were 52.2%, 56.3%, and 65.2%, respectively. Overall response rate was 47.4% among patients who had MM refractory to the third drug reintroduced in the Sd-based triplet. Median progression-free survival in the SPd, SVd, and SKd cohorts was 8.7, 6.7, and 15.0 months, respectively, and median overall survival was 9.6, 16.9, and 33.0 months, respectively. Median time to discontinuation in the SPd, SVd, and SKd cohorts was 4.4, 5.9, and 10.6 months, respectively. The most common hematological adverse events were thrombocytopenia, anemia, and neutropenia. Nausea, fatigue, and diarrhea were primarily grade 1/2. Adverse events were generally manageable with standard supportive care and dose modifications. CONCLUSION: Selinexor-based regimens may offer effective and well-tolerated therapy to patients with relapsed and/or refractory MM who had disease previously exposed or refractory to αCD38 mAb therapy and could help address the unmet clinical need in these high-risk patients.

First Line Treatment of Newly Diagnosed Transplant Ineligible Multiple Myeloma: Recommendations from the Canadian Myeloma Research Group Consensus Guideline Consortium.

Although the availability of effective novel treatments has positively impacted the quality of life and survival of newly diagnosed multiple myeloma (MM) patients, benefits in the transplant ineligible MM population may be limited by functional/frailty status. The Canadian Myeloma Research Group Consensus Guideline Consortium proposes consensus recommendations for the first-line treatment of transplant ineligible MM. To address the needs of physicians and people diagnosed with MM, this document further focuses on eligibility for transplant, frailty assessment, management of adverse events, assessment of treatment response, and monitoring for disease relapse. The Canadian Myeloma Research Group Consensus Guideline Consortium will periodically review the recommendations herein and update as necessary.

Real-world data on lenalidomide dosing and outcomes in patients newly diagnosed with multiple myeloma: Results from the Canadian Myeloma Research Group Database.

Using the Canadian Myeloma Research Group Database, a retrospective study of 167 newly diagnosed, transplant-ineligible patients with multiple myeloma (MM) that received lenalidomide-dexamethasone as front-line treatment was conducted to understand the impact of lenalidomide dosing. Starting dose modifications were common, 42% of patients started on lenalidomide <25 mg with normal renal function. During treatment course, 35% of patients required further dose reduction. Dose reductions in the first year did not have an impact on progression free survival or overall survival. Further studies need to be conducted to understand the impact of dosing strategies of anti-MM agents in the real world.

Selinexor-based regimens in patients with multiple myeloma after prior anti-B-cell maturation antigen treatment.

There is a lack of consensus on therapy sequencing in previously treated multiple myeloma, particularly after anti-B-cell maturation antigen (BCMA) therapy. Earlier reports on selinexor (X) regimens demonstrated considerable efficacy in early treatment, and after anti-BCMA-targeted chimeric antigen receptor-T cell therapy. Here, we present data from 11 heavily pretreated patients who predominantly received BCMA-antibody-drug conjugate therapy. We observe that X-containing regimens are potent and achieve durable responses with numerically higher overall response and clinical benefit rates, as well as median progression free survival compared to patients' prior anti-BCMA therapies, despite being used later in the treatment course. In an area of evolving unmet need, these data reaffirm the efficacy of X-based regimens following broader anti-BCMA therapy.

Carfilzomib usage patterns and outcomes in patients with relapsed multiple myeloma: A multi-institutional report from the Canadian Myeloma Research Group (CMRG) Database.

Carfilzomib is an active and commonly used treatment in patients with multiple myeloma (MM). Using the Canadian Myeloma Research Group Database, we performed a retrospective observational study of patients treated with carfilzomib for relapse of MM in a real-world setting in Canada between years 2007 and 2020. A total of 445 patients were included in this study: the doublet (Kd/p, n = 218) and triplets (KCd, n = 88; KRd, n = 99; KPd/p, n = 40). One hundred and twenty-two (27%) received carfilzomib-based treatment in line 2, 133 (30%) in line 3, 90 (20%) in line 4, and 100 (23%) in line 5 or higher. Carfilzomib was dosed weekly in 40% of patients and twice weekly in 60%. The overall response rate of the entire cohort was 57.7%, with 33.6% of patients achieving very good partial response or better. Median progression-free survival for the overall cohort was 6.3 months with overall survival 19.7 months. This study provides a benchmark for carfilzomib-based regimens in the real world, demonstrating that these regimens are effective in treating patients with relapsed MM.

Outcomes of daratumumab in the treatment of multiple myeloma: A retrospective cohort study from the Canadian Myeloma Research Group Database.

Daratumumab (dara) has significantly altered the therapeutic landscape of multiple myeloma (MM), especially in the relapsed setting. This study aimed to evaluate the outcomes of dara-containing regimens in the Canadian real-world setting among relapsed and refractory MM available within the national Canadian Myeloma Research Group Database (CMRG-DB). A total of 583 MM patients who received dara-based therapy in second-line or later treatment were included. After a median follow-up of 17.5 months, the median progression-free survival (PFS) and overall survival (OS) for the entire cohort were 13.1 and 32.9 months, respectively. The median PFS and OS were 23.5 and 49.1 months in second-line treatment and decreased to 12.8 and 43.0 months in third-line and 7.0 and 20.5 months in fourth-line treatment respectively. Dara in monotherapy with or without corticosteroids after a median of four prior lines of therapy resulted in a median PFS of 3.9 months and a median OS of 17.1 months. The addition of bortezomib, lenalidomide or pomalidomide to dara resulted in an improved median PFS and OS of 8.3 and 26.2 months; 26.8 and 43.0 months; and 9.7 and 31.4 months respectively. These retrospective data from the CMRG-DB suggest that outcomes are superior when dara is used in combination and in earlier lines of treatment.

Survival and Outcomes of Newly Diagnosed Multiple Myeloma Patients Stratified by Transplant Status 2007-2018: Retrospective Analysis from the Canadian Myeloma Research Group Database.

BACKGROUND: Considerable progress has been made in therapeutic options for multiple myeloma (MM). Understanding the current landscape of MM treatment options and associated outcomes in the real world is important in providing key insights into clinical and knowledge gaps which could be targeted for further optimization. METHODS: The Canadian Myeloma Research Group Database (CMRG-DB) is a prospectively maintained disease-specific database with >7000 patients. The objective of this study was to describe the trends in the treatment landscape and outcomes including early mortality, time to next treatment, and overall survival (OS) in each line of treatment stratified by autologous stem cell transplant (ASCT) receipt among newly-diagnosed MM patients in Canada between 2007 and 2018. RESULTS: A total of 5154 patients were identified among which 3030 patients (58.8%) received an upfront ASCT and 2124 (41.2%) did not. At diagnosis, the median age was 64 years and 58.6% were males. Bortezomib and lenalidomide were most frequently used (>50%) in first and second-line treatment respectively among both the ASCT and non-ASCT cohort. The median OS was 122.0 months (95% Cl 115.0-135.0 months) and 54.3 months (95% CI 50.8-58.8 months) for the ASCT and non-ASCT cohort respectively with an incremental decrease in OS in each subsequent line of treatment. CONCLUSION: We present the largest study to date in the Canadian landscape showing the characteristics, therapy usage, and outcomes among MM patients. This information will be critical in benchmarking current outcomes and provide key insight into areas of unmet needs and gaps for improvement of MM patients nationally.

Efficacy of Daratumumab-Containing Regimens Among Patients With Multiple Myeloma Progressing on Lenalidomide Maintenance: Retrospective Analysis.

BACKGROUND: Daratumumab, a monoclonal antibody directed against CD38 is a recent class of drugs introduced into the multiple myeloma therapeutic landscape. While clinical trial data have shown a remarkable impact on outcomes, the efficacy of daratumumab combination therapies in specific clinically relevant subgroups including among patients refractory to lenalidomide maintenance remains unknown. METHODS: In this study, retrospective data were reviewed from the Canadian Myeloma Research Group and the German Munster Myeloma databases to identify patients that received daratumumab in combination with pomalidomide (DPd), lenalidomide (DRd), and bortezomib (DVd) in a population that had relapsed on lenalidomide maintenance postautologous stem cell transplant. The primary aim of the study was to look at outcomes of these patients in different daratumumab combinations. RESULTS: A total of 73 patients were identified. The median age of the patients at the time of daratumumab initiation was 60 (38-72) and 64.4% (n = 47) were men. In the selected cohort, 43.8% (n = 32) were treated with DRd, 31.5% (n = 23) with DVd, and 24.7% (n = 18) with DPd regimen. The median progression-free survival (PFS) of the entire cohort was 15.8 months (95% CI, 12.9-37.1 months). The median PFS of the individual regimens was as follows: DPd 18.9 months (95% CI, 13.7-not reached), DRd 21.7 months (95% CI, 11.6-not reached), and DVd 12.9 months (95% CI, 3.1-not reached). CONCLUSIONS: Daratumumab-containing therapies are effective regimens in patients progressing on lenalidomide maintenance. Additional studies are required to decide the optimal regimen post-lenalidomide maintenance.

Sequential Use of Carfilzomib and Pomalidomide in Relapsed Multiple Myeloma: A Report from the Canadian Myeloma Research Group (CMRG) Database.

The treatment of multiple myeloma has dramatically improved due to the availability of novel therapies that are highly effective and are quickly moving into first-line therapy. The Canadian Agency for Drugs and Technologies in Health (CADTH) recently recommended that patients who receive daratumumab should only be eligible to receive either carfilzomib or pomalidomide but not both, for relapsed MM. In order to assess the efficacy of these two agents in the relapsed setting, we utilized our national myeloma database. A total of 121 patients were reviewed, 49 patients received CAR- before POM-based (CAR-POM), and 73 patients received POM- before CAR-based (POM-CAR) therapy. In the groups selected, the median PFS was 4.93 months (95% CI, 2.76-7.07) and 5.36 months (95% CI, 3.75-6.94) for CAR-POM and POM-CAR, respectively. The median OS for patients treated with CAR-POM was 11.01 months (95% CI, 4.50-19.13), and for patients treated with POM-CAR the median OS was 10.98 months (95% CI, 8.98-19.17). In this real-world observational study, we demonstrated that both CAR- and POM-based therapies, irrespective of the order in which they were used, were effective treatment options for patients with advanced relapsed MM.

Management of Myeloma Manifestations and Complications: The Cornerstone of Supportive Care: Recommendation of the Canadian Myeloma Research Group (formerly Myeloma Canada Research Network) Consensus Guideline Consortium.

Multiple myeloma (MM) is a hematological cancer associated with significant symptomatic burden. Bone disease, renal insufficiency, cytopenias, infection, and peripheral neuropathy, among other disease manifestations and complications, impair patients' quality of life. The Canadian Myeloma Research Group Consensus Guideline Consortium, formerly Myeloma Canada Research Network Consensus Guideline Consortium, proposes national consensus recommendations for the management of MM-related manifestations and complications. To address the needs of Canadian physicians and people living with MM across the country, this document focuses on the improvement and maintenance of patient care by clarifying best-practice approaches for the prevention, detection and management of disease manifestations and complications. The Canadian Myeloma Research Group Consensus Guideline Consortium will periodically review the recommendations herein and update as necessary.

Once weekly selinexor, carfilzomib and dexamethasone in carfilzomib non-refractory multiple myeloma patients.

BACKGROUND: Proteasome inhibitors (PIs), including carfilzomib, potentiate the activity of selinexor, a novel, first-in-class, oral selective inhibitor of nuclear export (SINE) compound, in preclinical models of multiple myeloma (MM). METHODS: The safety, efficacy, maximum-tolerated dose (MTD) and recommended phase 2 dose (RP2D) of selinexor (80 or 100 mg) + carfilzomib (56 or 70 mg/m2) + dexamethasone (40 mg) (XKd) once weekly (QW) was evaluated in patients with relapsed refractory MM (RRMM) not refractory to carfilzomib. RESULTS: Thirty-two patients, median prior therapies 4 (range, 1-8), were enrolled. MM was triple-class refractory in 38% of patients and 53% of patients had high-risk cytogenetics del(17p), t(4;14), t(14;16) and/or gain 1q. Common treatment-related adverse events (all/Grade 3) were thrombocytopenia 72%/47% (G3 and G4), nausea 72%/6%, anaemia 53%/19% and fatigue 53%/9%, all expected and manageable with supportive care and dose modifications. MTD and RP2D were identified as selinexor 80 mg, carfilzomib 56 mg/m2, and dexamethasone 40 mg, all QW. The overall response rate was 78% including 14 (44%) ≥ very good partial responses. Median progression-free survival was 15 months. CONCLUSIONS: Weekly XKd is highly effective and well-tolerated. These data support further investigation of XKd in patients with MM.