P979: PATIENT-REPORTED OUTCOMES FOR TECLISTAMAB VERSUS REAL-WORLD PHYSICIAN’S CHOICE OF THERAPY IN THE LOCOMMOTION STUDY IN PATIENTS WITH TRIPLE-CLASS EXPOSED RELAPSED/REFRACTORY MULTIPLE MYELOMA
2023-08-01

Topic: 14. Myeloma and other monoclonal gammopathies - Clinical Background: Indirect treatment comparisons between the phase 1/2 MajesTEC-1 study (NCT04557098) and real-world (RW) studies have shown improved effectiveness with teclistamab, a B-cell maturation antigen × CD3 bispecific antibody, over RW physician's choice (RWPC) of therapy in patients with triple-class exposed relapsed/refractory multiple myeloma (RRMM) who had received ≥3 prior lines of therapy (Krishnan et al, IMS 2022, P-251; Mateos et al, IMS 2022, P-281; van de Donk et al, IMS 2022, OAB-054). Here, we present patient-reported outcomes (PROs) for teclistamab in MajesTEC-1 vs those for RWPC in the prospective, noninterventional LocoMMotion study (NCT04035226). Aims: To report a comparative analysis of PROs from the MajesTEC-1 and LocoMMotion studies. Methods: PROs from the phase 2 portion of MajesTEC-1 (N=125, enrolled Oct 2020–Aug 2021; clinical cut-off, Mar 16, 2022) were compared with an external control arm of patients from LocoMMotion (N=248, enrolled Aug 2019–Oct 2020; clinical cut-off, Nov 2, 2021). All patients provided informed consent. PROs were assessed at baseline and on day 1 of every other treatment cycle (up to cycle 16) using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) and the EuroQol Five Dimension Five Level (EQ-5D-5L) questionnaires. Differences in changes from baseline (CFB) between both treatment cohorts were estimated for each PRO domain using a mixed model of repeated measures (MMRM), including baseline prognostic variables as covariates to adjust for confounding bias. MMRM analyses included patients with baseline and post-baseline PRO assessments (teclistamab, n=85; RWPC, n=170). PRO assessment was limited after disease progression; the MMRM approach does not account for the selective dropout of patients who progressed or died, which may underestimate the PRO benefit of teclistamab due to its longer progression-free survival and overall survival vs RWPC. To correct for this inherent survival bias, a responder analysis was performed for each PRO domain, estimating the percentage of patients who were progression-free with clinically meaningful changes in outcomes, defined by a threshold of ≥10 points on a 1–100 scale, over time. Results: Estimates for mean differences in CFB were significantly in favor of teclistamab over RWPC (P<0.05) for several PRO domains, including the EQ-5D-5L visual analogue score (VAS; 4.5), the EORTC QLQ-C30 global health score (GHS; 6.5), emotional functioning (7.4), pain (–6.2), and dyspnea (–9.5) (Table). There were no domains that significantly improved in favor of RWPC over teclistamab. At 9 months, responder analyses showed significantly more patients with clinically meaningful improvement for teclistamab over RWPC for VAS (27.5% vs 6.4%); GHS (24.1% vs 10.3%); functional PROs, including physical (17.2% vs 10.3%), role (25.9% vs 10.3%), social (22.4% vs 9.0%), cognitive (10.3% vs 5.1%), and emotional (27.6% vs 3.9%); and symptom PROs, including nausea and vomiting (10.3% vs 3.9%), diarrhea (17.2% vs 5.1%), appetite loss (12.1% vs 1.3%), and insomnia (15.5% vs 7.7%) (all P<0.05). Summary/Conclusion: Teclistamab showed significantly improved PROs over RWPC in patients with triple-class exposed RRMM. This highlights the positive impact teclistamab can have on health-related quality of life in addition to significant efficacy benefits to help address the high unmet need for this patient population.Keywords: Real world data, Patient reported outcomes, Multiple myeloma, Clinical trial