Carfilzomib-Lenalidomide-Dexamethasone Versus Bortezomib-Lenalidomide-Dexamethasone in Patients with Newly Diagnosed Multiple Myeloma: Results from the Prospective, Longitudinal, Observational Commpass Study
Authors: Landgren Ola , Siegel David S , Auclair Daniel , Chari Ajai , Boedigheimer Michael , Welliver Tim , Mezzi Khalid , Iskander Karim , Jakubowiak Andrzej 
Published: October 2019

Abstract
Introduction: Triplet regimens incorporating a proteasome inhibitor and immunomodulatory drug are standards of care for the treatment of patients with newly diagnosed multiple myeloma (NDMM). The combinations of carfilzomib-lenalidomide-dexamethasone (KRd) and bortezomib-lenalidomide-dexamethasone (VRd) are recommended regimens for the treatment of NDMM by the National Comprehensive Care Network. However, there are limited data directly comparing the relative effectiveness and tolerability of these two regimens in patients with NDMM. Here, we report prospective evaluation of efficacy and preliminary tolerability data for patients who received KRd or VRd as frontline therapy in the Multiple Myeloma Research Foundation (MMRF) Clinical Outcomes in MM to Personal Assessment of Genetic Profile (CoMMpass, NCT01454297) study.
Methods: CoMMpass is a prospective observational study conducted since 2011 by the MMRF that has enrolled over 1100 patients from Multiple Myeloma Research Consortium sites. Eligible adults with NDMM and symptomatic disease were enrolled within 30 days of initiating frontline therapy. Frontline therapy was chosen at the discretion of the investigator but must have included a proteasome inhibitor and/or immunomodulatory drug. In the current analysis, we evaluated the effectiveness and reasons for treatment discontinuation among enrolled patients who received KRd or VRd as first-line therapy. KRd patients were matched to VRd patients based on propensity score matching including age, gender, ISS and renal insufficiency as covariates. Treatment response was assessed by investigators and defined by International Myeloma Working Group Uniform Response Criteria. Event-free survival (EFS) was the pre-specified primary endpoint and defined as the time from the start of treatment until disease progression, death, or the initiation of new therapy. EFS was compared between treatment groups using a Cox proportional hazards model.
Results: A total of 609 evaluable patients received first-line KRd (n=149) or VRd (n=460). Of these, 149 KRd patients and 149 VRd patients were matched according to baseline co-variates. Patient demographics and disease characteristics were balanced between treatment arms for the matched set of patients (KRd vs VRd) including by median age (years, 58 vs 59), gender (male, 63% vs 62%), and ISS (stage I, 46% vs 53%; stage II, 41% vs 40%; stage III, 13% vs 7%). With median follow up of 11.5 months for KRd and 41.9 months for VRd, 12-month EFS rates (95% CI) were 95% (90-99%) for KRd vs 84% (78-90%) for VRd (12-month HR, 0.28; 95% CI, 0.10-0.75; p=0.0043; Figure 1). By 12 months, 87% (95% CI, 81-93%) of KRd patients vs 68% (95% CI, 60-76%) of VRd patients had a partial response or better (p=0.0029) and 35% (95% CI, 25-45%) of KRd patients vs 14% (95% CI, 8-20%) of VRd patients achieved a complete response or better (p=0.0054; Figure 2). The treatment discontinuation rate due to adverse events was 3.4% for each arm.
Conclusions: In the CoMMpass study, KRd demonstrated significant improvements in 12-month EFS compared with VRd in patients with NDMM (HR, 0.28; 95% CI, 0.10-0.75; p=0.0043). By 12 months, patients treated with KRd also achieved significantly higher response rates and complete response rates or better compared with VRd treated patients. Discontinuation rates due to AEs were similar between KRd and VRd. With limitations of non-randomized evaluation and relatively short median follow-up in the KRd arm, these results are consistent with previous single arm studies that KRd is not only effective but potentially a superior treatment option compared with VRd for patients with NDMM. Updated results with extended follow-up will be presented.

Disclosures
Landgren: Karyopharm: Consultancy; Pfizer: Consultancy; Celgene: Consultancy, Research Funding; Amgen: Consultancy, Research Funding; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Membership on an entity's Board of Directors or advisory committees. Siegel:Novartis: Honoraria, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau; BMS: Consultancy, Honoraria, Speakers Bureau; Takeda: Consultancy, Honoraria, Speakers Bureau; Merck: Consultancy, Honoraria, Speakers Bureau; Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau; Karyopharm: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Speakers Bureau. Chari:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmacyclics: Research Funding; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Array Biopharma: Research Funding; Adaptive Biotechnology: Membership on an entity's Board of Directors or advisory committees; The Binding Site: Consultancy; Bristol Myers Squibb: Consultancy. Boedigheimer:Amgen Inc.: Employment, Equity Ownership. Welliver:Amgen: Employment, Equity Ownership. Mezzi:Amgen: Employment, Equity Ownership. Iskander:Amgen: Employment, Equity Ownership. Jakubowiak:Amgen: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria; Adaptive Biotechnologies: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria; SkylineDx: Consultancy, Honoraria; Celgene: Consultancy, Honoraria.