Background:
Substantial improvements in both progression free survival (PFS) and overall survival (OS) have been observed in patients with multiple myeloma over recent years. Despite these therapeutic advances, multiple myeloma remains incurable, and most patients eventually progress through standard drug classes of proteasome inhibitors (PIs), immunomodulatory drugs (IMiDs), anti-CD38 monoclonal antibodies (mAbs) and others. Understanding the effectiveness of current standards of care in heavily pretreated patients with relapsed and / or refractory multiple myeloma (RRMM) remains an area of unmet need, and there are currently no prospective data reflecting real-world practice in this patient population progressing after PIs, IMiDs and anti-CD38 mAbs.
Study design:
This prospective multinational efficacy and safety study of real-life current standards of care (real-life SOC) will be conducted in the USA and Europe in approximately 230 adult patients with RRMM who received at least 3 prior lines of therapy or are double refractory to PI & IMiD and have received at least a PI, an IMiD, and CD38 mAbs and with documented progressive disease (PD) since their last line of therapy and have an ECOG score of 0-1. Also, subjects with documented evidence of PD (as above) within the previous 6 months and who are refractory or non-responsive to their most recent line of treatment are eligible. There are no exclusion criteria due to the observational nature of the study. The treatments that these patients receive in real life will be assessed for safety and efficacy over a two-year period.
Real-life SOC treatments are defined as the treatment used in local clinical practice by the investigator for adult subjects with RRMM, who meet the eligibility criteria. Subject participation will include a Screening Phase, a Treatment Phase, and a Follow-up Phase up to 24 months from day 1, cycle 1 of the treatment. The Follow-up Phase will continue until study completion, which is defined as 24 months after the last subject receives the first dose of real life SOC treatment. Subjects will be treated until disease progression, unacceptable toxicity, or other reasons.
The primary objective of the study is to evaluate the overall response rate (ORR) of real-life SOC treatments in participants with RRMM patients. The secondary and exploratory objectives of the study are the further evaluation of the clinical benefit, patient-reported outcomes (PROs), safety and the potential correlation of rate of minimal residual disease (MRD) negativity with duration of response (DOR), PFS and OS.
Methods:
Demographic and patient characteristics, clinical response parameters, PRO measures, health care resource utilization, and safety data will be descriptively summarized. Due to the observational nature of the study, there is no direct hypothesis being tested. Therefore, the sample size is based on the clinically acceptable precision of the 95% confidence interval for the primary objective of describing ORR under real-life current SOC treatment. For the primary endpoint exact 95% confidence intervals by the Clopper-Pearson method will be calculated. For therapies available to treat participants with RRMM the reported ORR is 30% or less. When the sample size is 230, using the large sample normal approximation, the width of a two-sided 95% confidence interval for the observed proportion will vary from 0.107 to 0.130 for an expected proportion varying from 0.20 to 0.40.
Moreau:AbbVie: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Celgene: Consultancy, Honoraria. Mateos:Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; GSK: 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: Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pharmamar: Membership on an entity's Board of Directors or advisory committees; EDO: Membership on an entity's Board of Directors or advisory committees; Adaptive: Honoraria; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees. Weisel:Takeda: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Research Funding; Sanofi: Consultancy, Honoraria, Research Funding; GSK: Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Adaptive Biotech: Consultancy, Honoraria; Juno: Consultancy. San-Miguel:Amgen, Bristol-Myers Squibb, Celgene, Janssen, MSD, Novartis, Roche, Sanofi, and Takeda: Consultancy, Honoraria. Facon:Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Boccadoro:Sanofi: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Bristol-Myers Squibb: Honoraria, Research Funding; AbbVie: Honoraria; Mundipharma: Research Funding; Amgen: Honoraria, Research Funding; Janssen: Honoraria, Research Funding. Goldschmidt:ArtTempi: Honoraria; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Grants and/or provision of Investigational Medicinal Product, Research Funding; Mundipharma: Research Funding; MSD: Research Funding; Novartis: Honoraria, Research Funding; Amgen: Membership on an entity's Board of Directors or advisory committees, Other: Grants and/or provision of Investigational Medicinal Product, Research Funding; Chugai: Honoraria, Other: Grants and/or provision of Investigational Medicinal Product, Research Funding; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Grants and/or provision of Investigational Medicinal Product, Research Funding; Molecular Partners: Research Funding; John Hopkins University: Other: Grants and/or provision of Investigational Medicinal Product; Dietmar-Hopp-Foundation: Other: Grants and/or provision of Investigational Medicinal Product; Adaptive Biotechnology: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other, Research Funding; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Grants and/or provision of Investigational Medicinal Product, Research Funding. Cavo:Janssen, Celgene: Other: Travel Accommodations; Janssen, Celgene, Amgen, Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen, Celgene: Speakers Bureau; Celgene, Janssen, Amgen, BMS, Abbvie, Takeda: Honoraria. Kaiser:Abbvie, Celgene, Takeda, Janssen, Amgen, Abbvie, Karyopharm: Consultancy; Celgene, Janssen: Research Funding; Takeda, Janssen, Celgene, Amgen: Honoraria, Other: Travel Expenses. Gay:Janssen: 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; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie: Membership on an entity's Board of Directors or advisory committees; Takeda: 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; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie: Membership on an entity's Board of Directors or advisory committees. Scheid:Janssen: Consultancy, Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Bristol Myers Squibb: Honoraria; Amgen: Consultancy, Honoraria; Celgene: Honoraria; Takeda: Honoraria, Research Funding. Broyl:Celgene, amgen, Janssen,Takeda: Honoraria. Van De Donk:AMGEN: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bayer: Membership on an entity's Board of Directors or advisory committees; Servier: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees. Potamianou:Janssen-Cilag: Employment. Sakabedoyan:Janssen-Cilag: Employment. Strulev:Jansen Pharmaceutica NV: Employment. Nesheiwat:Legend Biotech: Employment, Equity Ownership. Bergmans:Janssen-Cilag: Employment. Rizvi:Legend Biotech: Employment, Equity Ownership. Pilatowicz:Janssen-Cilag: Employment. Sonneveld:Amgen: Honoraria, Research Funding; BMS: Honoraria; Celgene: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Karyopharm: Honoraria, Research Funding; Takeda: Honoraria, Research Funding; SkylineDx: Research Funding.
Author notes
Asterisk with author names denotes non-ASH members.
