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.

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.

SARS-CoV-2 and cancer: the intriguing and informative cross-talk.

The COVID-19 pandemic caused by the SARS-CoV-2 virus has significantly disrupted and burdened the diagnostic workup and delivery of care, including transfusion, to cancer patients across the globe. Furthermore, cancer patients suffering from solid tumors or hematologic malignancies were more prone to the infection and had higher morbidity and mortality than the rest of the population. Major signaling pathways have been identified at the intersection of SARS-CoV-2 and cancer cells, often leading to tumor progression or alteration of the tumor response to therapy. The reactivation of oncogenic viruses has also been alluded to in the context and following COVID-19. Paradoxically, certain tumors responded better following the profound infection-induced immune modulation. Unveiling the mechanisms of the virus-tumor cell interactions will lead to a better understanding of the pathophysiology of both cancer progression and virus propagation. It would be challenging to monitor, through the different cancer registries, retrospectively, the response of patients who have been previously exposed to the virus in contrast to those who have not contracted the infection.

Real-world outcomes with bortezomib-containing regimens and lenalidomide plus dexamethasone for the treatment of transplant-ineligible multiple myeloma: a multi-institutional report from the Canadian Myeloma Research Group database.

Bortezomib-containing regimens (BCRs) represented standard, first-line therapy for transplant-ineligible multiple myeloma (TIMM) in Canada until the introduction of lenalidomide and low-dose dexamethasone (Ld). However, little comparative data exist to inform the selection of regimens. We assessed the outcomes for TIMM patients treated with cyclophosphamide, bortezomib and dexamethasone or prednisone (CyBorD/P), bortezomib, melphalan and prednisone (VMP), bortezomib and dexamethasone or prednisone (VD/P) and lenalidomide and low-dose dexamethasone (Ld) using the Canadian Myeloma Research Group database. Of 1156 TIMM patients evaluated, 82% received bortezomib combinations while 18% received Ld. Median progression-free survival (PFS) was 21·0, 21·1, 13·2 and 28·5 months (P = 0·0002) and median overall survival (OS) was 52·0, 63·6, 30·8 and 65·7 months (P < 0·0001) in the CyBorD/P, VMP, VD/P and Ld groups respectively. There was no significant difference in PFS and OS between the two triplet bortezomib regimens (VMP and CyBorD/P). Ld was associated with a longer PFS but not a significantly superior OS to date. Outcomes with the bortezomib-steroid doublet were inferior (VD/P). However, multivariable analysis identified features related to disease biology as the most important prognostic factors for PFS and OS. Such factors, as well as those affecting the physician's choice of regimen, are likely to influence the results observed with different regimens. This study demonstrated real-world outcomes in TIMM similar to those reported in clinical trials.

The impact of lenalidomide maintenance on second-line chemotherapy in transplant eligible patients with multiple myeloma.

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.

Retrospective study of treatment patterns and outcomes post-lenalidomide for multiple myeloma in Canada.

Lenalidomide is an important component of initial therapy in newly diagnosed multiple myeloma, either as maintenance therapy post-autologous stem cell transplantation (ASCT) or as first-line therapy with dexamethasone for patients' ineligible for ASCT (non-ASCT). This retrospective study investigated treatment patterns and outcomes for ASCT-eligible and -ineligible patients who relapsed after lenalidomide as part of first-line therapy, based on data from the Canadian Myeloma Research Group Database for patients treated between January 2007 and April 2019. Among 256 patients who progressed on lenalidomide maintenance therapy, 28.5% received further immunomodulatory derivative-based (IMiD-based) therapy (lenalidomide/pomalidomide) without a proteasome inhibitor (PI) (bortezomib/carfilzomib/ixazomib), 26.2% received PI-based therapy without an IMiD, 19.5% received both an IMiD plus PI, 13.5% received daratumumab-based regimens, and 12.1% underwent salvage ASCT. Median progression-free survival (PFS) was longest for daratumumab-based therapy (22.7 months) and salvage ASCT (23.4 months) and ranged from 6.6 to 7.3 months for the other treatments (P < .0001). Median overall survival (OS) was also longest for daratumumab and salvage ASCT. A total of 87 non-ASCT patients received subsequent therapy, with 66.7% receiving bortezomib-based therapy and 13.8% receiving other PI-based therapy. Median PFS was 15.4 and 24.8 months for bortezomib-based and other PI-based therapy, respectively (P = .404). During most of the study period, daratumumab was not funded; in this setting, switching to a different therapeutic class following relapse on lenalidomide produced the longest remissions for non-ASCT patients. Further prospective studies are warranted to determine optimum treatment following relapse on lenalidomide, especially in the light of increased access to daratumumab.

Transfusion challenges in hematology oncology and hematopoietic stem cell transplant - Literature review and local experience.

Transfusion medicine plays a vital role in the supportive care of patients receiving therapy for hematology, oncology and hematopoietic stem cell transplants (HSCT). With advances in therapy with more intensive chemotherapy or radiotherapy, patients usually develop cytopenias and need frequent transfusion support with packed red blood cells, granulocyte transfusion or platelets to support them until they recover from the effect of therapy. HSCT poses unique challenges for transfusion medicine, since transplant recipients may require substantial transfusion support due to cytopenias associated with toxic medications, decreased marrow reserve, infection or their malignancy. Transfusion support has many complications, mainly immune mediated and infectious complications. Jehovah's Witness patients deny transfusions of blood products as a therapeutic option and, consequently, management of their disease with chemotherapy and stem cell transplant after myeloablative therapy is quite challenging. This review describes the challenges of transfusion support in managing hemato-oncology and stem cell transplant patients and highlights a local experience in transplanting two Jehovah's Witness patients.

Platelet microparticle: a sensitive physiological "fine tuning" balancing factor in health and disease.

Platelet microparticles (PMPs) have long been regarded as inert "platelet dusts". They have now taken a center stage on the clinical research scene of transfusion medicine, being actually seen as long-stretch hands of platelets that exert a physiological role beyond the initial site of activation. These 0.05 µm to 0.8 µm microvesicles, delimited by a phospholipidic bilayer, are released by platelet membranes following activation by agonists, complement activation, or high shear forces. They can also be generated as a result of platelets and megakaryocyte senescence or cytoskeletal abnormalities. PMPs may orchestrate a delicate hemostatic balance in health, and act as procoagulant vectors in diseases triggering thrombosis. Furthermore, through their potential cargo of growth factors, microRNA and various bioactive molecules, they may promote healing in health, but, on the other side of the coin, can act as pro-inflammatory carriers and may contribute to cancer growth as an actor of the platelet-cancer loop. Through their cellular interactions they also interplay with the immune system. Their capacity to be generated by shear forces and contact with surfaces during the processing of blood and blood components, which may trigger transfusion reactions, make them also an integral part of transfusion medicine. Given their documented association with pathological conditions, PMP may serve as biomarkers for disease status or as a possible new target for anti-platelet drugs to treat cancer or inflammation.

Platelet-cancer interactions.

Platelets play a crucial role in the pathophysiological processes of hemostasis and thrombosis. Increasing evidence indicates that they fulfill much broader roles in balancing health and disease. The presence of tumor cells affects platelets both numerically, through a wide variety of mediators and cytokines, or functionally through tumor cell-induced platelet activation, the first step toward cancer-induced thrombosis. This induction results from signaling events through the different platelet receptors, or may be cytokine-mediated. Reciprocally, upon activation, the platelets will release a myriad of growth factors from their dense and α-granules and peroxisomes; these will directly impact tumor growth, tethering, and spread. A similar cross-talk is initiated between tumor microvesicles stimulating the platelets and platelet microparticles, promoting both thrombosis and tumor growth. A vicious loop of activation thereafter takes place. Platelets directly and indirectly promote tumor growth, and enable a molecular mimicry coating the malignant growth and allowing metastasizing cells to escape T-cell-mediated immunity and natural killer cell surveillance. Breaking this vicious activation loop with nonspecific platelet inhibitors, such as aspirin, or by targeting specific sites on the activation cascade may offer a mean to reduce both the risks of development and progression of cancer and the risk of thrombosis.

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.

A Phase II, Open-Label Study of an Accelerated Infusion Rate of Daratumumab in Patients With Relapsed and Refractory Multiple Myeloma.

INTRODUCTION/BACKGROUND: Daratumumab is an anti-CD38 monoclonal antibody initially approved as a single agent for the treatment of relapsed and refractory multiple myeloma. The infusion-related reactions (IRRs) commonly seen with intravenous daratumumab have been managed by prolonging the first infusion, temporarily stopping/slowing the rate if reactions occur and using adequate pre- and post-infusion medications. Several retrospective studies have evaluated shorter infusions after ≥ 2 prior doses administered at the standard rates. Although the shorter infusions were well-tolerated, patients in these reports were given heterogeneous daratumumab regimens and had often already received multiple doses at the longer standard rates. PATIENTS AND METHODS: CMRG-009 is a prospective study designed to demonstrate the safety of accelerated daratumumab infusions commencing with the second dose. After an initial dose on Cycle 1 Day consisting of 8 mg/kg over 4 hours, all subsequent doses were given over 90 minutes. RESULTS: No grade 3 IRRs were observed with the 90-minutes infusions. Both the safety profile and anti-myeloma effects were otherwise similar to those observed with other single agent daratumumab studies using longer infusion times. CONCLUSION: This is the first formal prospective trial using infusion times shorter than the standard schedule directly after an initial 4-hours dose. This rapid infusion protocol has resulted in more efficient resource utilization and has become the standard protocol for the use in all intravenous daratumumab regimens in Canada. This approach has been particularly helpful in shortening chair time during the COVID-19 pandemic and providing a useful alternative in jurisdictions without access to subcutaneous daratumumab.

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.

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.

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.

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.

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.

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.