Abstract
Introduction: The introduction of new treatments over the past 2 decades has improved survival outcomes in patients with multiple myeloma (MM), yet MM remains incurable. Despite therapeutic advances, most patients with MM eventually relapse and/or become refractory to treatment, and cycle through standard drug classes of proteasome inhibitors (PIs), immunomodulatory drugs (IMiDs), and anti-CD38 monoclonal antibodies (mAbs), becoming triple-class exposed. These triple-class exposed patients represent a population with an urgent unmet clinical need and are a major focus for the development of new therapies. There are currently no prospective data outside of clinical trials on standard-of-care (SOC) in MM patients who progress after these treatment regimens. LocoMMotion (NCT04035226) is the first prospective study to assess the efficacy and safety of real-life SOC treatments in triple-class exposed patients with relapsed/refractory MM (RRMM). Initial analysis at a median follow-up of 3.7 months (range: 0.0-12.7) showed an overall response rate (ORR) of 20.1% (95% CI: 15.0-26.0), with only 5% of patients achieving very good partial response or better. Here, we report updated results from LocoMMotion with a longer median duration of follow-up (7.8 months), along with progression-free survival (PFS) and overall survival (OS) data.
Methods: LocoMMotion is a non-interventional study of 246 patients across 10 countries (the US and 9 in Europe) and 75 sites. Patients (aged ≥18 years) with a documented diagnosis of MM were included if they received ≥3 prior lines of therapy or were double-refractory to a PI and IMiD; had measurable disease at screening; received at least a PI, an IMiD, and anti-CD38 mAb with documented progressive disease since their last line of therapy; and had an Eastern Cooperative Oncology Group performance status (ECOG PS) score of 0 or 1. Patient-level data and the most common SOC treatments were collected and analyzed during the study period (August 2019 through October 2020). Real-life SOC treatments were defined as those used in local clinical practice. Responses were assessed per International Myeloma Working Group response criteria. A review committee assessed the ORR (primary objective) of real-life current SOC as well as disease progression for the determination of PFS. Secondary objectives included evaluation of additional efficacy endpoints, including OS, and safety.
Results: As of the data cut-off date of March 9, 2021, 246 patients were included with a median follow-up of 7.8 months (range: 0.1-16.9); 23 (9.3%) patients were from the US and 223 (90.7%) were from Europe. Median age was 68 years (range: 41-89), 133 (54.1%) were male, 180 (73.8%) had a baseline ECOG PS score of 1, and median time since initial MM diagnosis was 6.3 years (range: <1.0-22.8). Patients had received a median of 4.0 prior lines of therapy (range: 2-13); all patients were triple-class exposed, 185 (75.2%) were triple-class refractory, and 228 (92.7%) were refractory to last line of therapy. Ninety-three unique treatment regimens were used in the enrolled population, and 63% of patients were treated with a combination of ≥3 drugs. ORR with real-life SOC salvage therapy was 28.0% (95% CI: 22.5-34.1). For the 69 patients who responded, median duration of response was 5.1 months (95% CI: 4.4-NE). In all patients treated, the median PFS was 4.4 months (95% CI: 3.8-5.4), and median OS was 12.4 months (95% CI: 9.6-NE). Treatment-emergent adverse events (TEAEs) were reported in 192 (78.0%) patients; 122 (49.6%) patients had grade ≥3 TEAEs. The most common grade ≥3 TEAEs were anemia (9.8%), thrombocytopenia (13.4%), and neutropenia (11.8%). Nineteen (7.7%) patients died due to TEAEs during the study; the most common TEAE leading to death was infection (n=11). Eighty (32.5%) patients had ongoing SOC treatment after the median follow up of 7.8 months. The study is ongoing in 147 (59.8%) patients.
Conclusions: Updated results of this first, prospective study of real-life SOC treatment in triple-class exposed patients with RRMM confirm rapid disease progression after application of salvage therapy and poor outcomes with currently available treatments. New treatment approaches with novel therapies are needed to improve outcomes in this patient population.
Moreau: Oncopeptides: Honoraria; Amgen: Honoraria; Abbvie: Honoraria; Janssen: Honoraria; Sanofi: Honoraria; Celgene BMS: Honoraria. Weisel: Roche: Honoraria; Oncopeptides: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Karyopharm: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Adaptive Biotechnologies: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; GSK: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Consultancy; Novartis: Honoraria; Pfizer: Honoraria. Goldschmidt: Incyte: Research Funding; BMS: Consultancy, Honoraria, Other: Grants and/or Provision of Investigational Medicinal Product, Research Funding; Celgene: Consultancy, Honoraria, Other: Grants and/or Provision of Investigational Medicinal Product, Research Funding; Chugai: Honoraria, Other: Grants and/or Provision of Investigational Medicinal Product, Research Funding; GSK: Honoraria; Amgen: Consultancy, Honoraria, Other: Grants and/or Provision of Investigational Medicinal Product, Research Funding; Janssen: Consultancy, Honoraria, Other: Grants and/or Provision of Investigational Medicinal Product, Research Funding; Johns Hopkins University: Other: Grant; Molecular Partners: Research Funding; MSD: Research Funding; Mundipharma: Research Funding; Novartis: Honoraria, Research Funding; Dietmar-Hopp-Foundation: Other: Grant; Sanofi: Consultancy, Honoraria, Other: Grants and/or Provision of Investigational Medicinal Product, Research Funding; Takeda: Consultancy, Research Funding; Adaptive Biotechnology: Consultancy. Delforge: Amgen, Celgene, Janssen, Sanofi: Honoraria, Research Funding. Mohty: Novartis: Honoraria; Astellas: Honoraria; Gilead: Honoraria; Bristol Myers Squibb: Honoraria; Pfizer: Honoraria; Adaptive Biotechnologies: Honoraria; Sanofi: Honoraria, Research Funding; Jazz: Honoraria, Research Funding; Takeda: Honoraria; Celgene: Honoraria, Research Funding; Amgen: Honoraria; Janssen: Honoraria, Research Funding. Cavo: Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Honoraria; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Accommodations, Speakers Bureau; Adaptive Biotechnologies: Consultancy, Honoraria; GlaxoSmithKline: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES, Speakers Bureau; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Bristol-Myers Squib: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Vij: BMS: Research Funding; Takeda: Honoraria, Research Funding; Sanofi: Honoraria, Research Funding; BMS: Honoraria; GSK: Honoraria; Oncopeptides: Honoraria; Karyopharm: Honoraria; CareDx: Honoraria; Legend: Honoraria; Biegene: Honoraria; Adaptive: Honoraria; Harpoon: Honoraria. Dytfeld: Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen Cilag: Consultancy, Current Employment, Honoraria, Membership on an entity's Board of Directors or advisory committees. Angelucci: Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene BSM: Honoraria, Other: DMC; Blue Bird Bio: Honoraria, Membership on an entity's Board of Directors or advisory committees; Menarini-Stemline: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: steering commitee, Speakers Bureau; Vertex Pharmaceuticals: Honoraria, Other: DMC; Crispr therapeutics: Honoraria, Other: DMC; Glaxo: Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees. Perrot: GSK: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Honoraria; Sanofi: Honoraria, Research Funding; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Benjamin: Servier: Honoraria, Research Funding; Allogene: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; BMS: Honoraria, Research Funding; Gileai: Honoraria, Research Funding. Van de Donk: BMS/Celgene: Consultancy, Honoraria; Janssen: Consultancy, Research Funding; Amgen: Consultancy, Research Funding; Cellectis: Research Funding; Takeda: Consultancy; Roche: Consultancy; Novartis /bayer/servier: Consultancy. Ocio: MSD: Honoraria; Amgen: Consultancy, Honoraria; Bristol-Myers Squibb/Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Speakers Bureau; Takeda: Consultancy, Honoraria, Speakers Bureau; Sanofi: Consultancy, Honoraria; Karyopharm: Consultancy; Oncopeptides: Consultancy, Honoraria; Pfizer: Consultancy; Secura-Bio: Consultancy. Scheid: Roche: Consultancy; Abbvie: Honoraria; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees. Gay: Oncopeptides: Membership on an entity's Board of Directors or advisory committees; Bluebird Bio: Membership on an entity's Board of Directors or advisory committees; Adaptive Biotechnologies: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline: Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Honoraria; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Consultancy, Honoraria. Rodriguez-Otero: Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Clínica Universidad de Navarra: Current Employment; Celgene-BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; GSK: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; Kite: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria; Regeneron: Honoraria. Broyl: Celgene: Honoraria; Janssen Pharmaceuticals: Honoraria; Sanofi: Honoraria; Bristol-Meyer Squibb: Honoraria; Amgen: Honoraria. Potamianou: Janssen: Current Employment, Current holder of stock options in a privately-held company. Sakabedoyan: Janssen: Current Employment. Semerjian: Janssen: Current Employment. Keim: Janssen Research & Development: Current Employment. Strulev: Janssen Pharmaceutica NV: Current Employment. Schecter: Janssen: Current Employment, Current holder of stock options in a privately-held company. Vogel: Janssen Global Services, LLC: Current Employment, Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company, Divested equity in a private or publicly-traded company in the past 24 months. Wapenaar: Janssen: Current Employment; Johnson & Johnson: Current holder of individual stocks in a privately-held company. Nesheiwat: Legend Biotech USA: Current Employment. San-Miguel: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, GlaxoSmithKline, Janssen, Karyopharm, Merck Sharpe & Dohme, Novartis, Regeneron, Roche, Sanofi, SecuraBio, and Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees. Sonneveld: SkylineDx: Honoraria, Research Funding; Karyopharm: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Celgene/BMS: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Research Funding. Einsele: Janssen, Celgene/BMS, Amgen, GSK, Sanofi: Consultancy, Honoraria, Research Funding. Mateos: Oncopeptides: Honoraria; GSK: Honoraria; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Regeneron: Honoraria, Membership on an entity's Board of Directors or advisory committees; Adaptive Biotechnologies: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bluebird bio: Honoraria; Celgene - Bristol Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie: Honoraria; Oncopeptides: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sea-Gen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees.
