LocoMMotion: a prospective, observational, multinational study of real-life current standards of care in patients with relapsed/refractory multiple myeloma-final analysis at 2-year follow-up

Topic: 14. Myeloma and other monoclonal gammopathies - Clinical Background: LocoMMotion (NCT04035226) is the first prospective observational study to assess effectiveness and safety of real-life standard of care (SOC) treatments (tx) for triple-class exposed (TCE) patients (pts) with relapsed/refractory multiple myeloma (RRMM). Effectiveness assessment by response review committee (RRC) (N=248; median follow-up 16.1 months [mo]) showed a low overall response rate (ORR) to SOC tx (31.5% [95%CI 25.7–37.6]), rapid disease progression (median progression-free survival [mPFS], 4.6 mo [95%CI 3.9–5.6]), and short median overall survival (mOS, 13.8 mo [95%CI 10.8–18.5]) (Moreau et al, IMS 2022, data cut-off Nov 2021). Here we report final results with longer median study follow-up and details of subsequent lines of therapy (LOT). Aims: To report effectiveness and safety data from final analysis of LocoMMotion study. Methods: TCE pts (≥18 yr) with documented MM, either double refractory to a PI and IMiD or with ≥3 prior LOT were enrolled after giving informed consent. Pts had documented progressive disease (PD) since last LOT and Eastern Cooperative Oncology Group performance status ≤1. Pt-level data and choice of tx (index LOT [ie, first tx upon study enrollment; approved therapies only] and subsequent LOT [experimental tx allowed]) were collected for 24 mo after first index LOT dosing of last pt enrolled. Responses were assessed by RRC per International Myeloma Working Group response criteria. Primary effectiveness endpoint was ORR, secondary endpoints included additional effectiveness endpoints and safety. Variables were summarized using descriptive statistics. ORR was reported with corresponding 95% Clopper-Pearson (exact) CIs. Time-to-event data were summarized by Kaplan-Meier methods. Results: Study period was Aug 2019 to Oct 2022 with median follow-up 26.4 mo (95%CI 25.0–28.1). N=248, median age 68 yr (range 41–89), and 135 pts (54.4%) were male. At baseline, pts had received a median of 4 prior LOT (range 2–13), 182 (73.4%) were triple-class refractory, 229 (92.3%) were refractory to last prior LOT, and 160 (64.5%) pts had prior stem cell transplantation (SCT). 91 unique tx regimens were used in index LOT, 162 (65.3%) pts had ≥3 drugs, 6 (2.4%) had SCT. Median duration of treatment (mDOT) was 4.0 mo (range 0.1–33.6). ORR was 31.9% (95%CI 26.1–38.0); median duration of response was 7.4 mo (95%CI 4.9–11.1), mPFS and mOS were 4.6 mo (95%CI 3.9–5.6) and 13.8 mo (95%CI 10.8–17.0), respectively. 12- and 24-mo PFS rates were 21.0% (95%CI 15.3–27.3) and 10.5% (95%CI 6.1–16.3). 12- and 24-mo OS rates were 53.4% (95%CI 46.7–59.6) and 33.7% (95%CI 27.3–40.2). 152 pts (61.3%) had subsequent LOT (1 subsequent LOT only n=78; ≥2 subsequent LOT n=74; Table 1). mPFS2 (ie, from start of study through subsequent LOT1) was 10.8 mo (95%CI 8.4–13.0). 79 different regimens were used in subsequent LOT1 with mDOT 2.8 mo (range 0–29.7). BCMA-targeted therapy use increased to 24.2% in subsequent LOT from 2.8% in index LOT. During index LOT 86.7% of pts experienced an adverse event (AE), most commonly cytopenias; 13 (5.2%) pts developed a second primary malignancy (index LOT n=5; after index LOT n=8). 158 pts (63.7%) died during the study; 67.7% of deaths were due to PD and 15.8% due to AEs (Table 2). Summary/Conclusion: Final analysis (median study follow-up >2 yr) of the first prospective study of real-life tx for TCE pts with RRMM shows a lack of well-established SOC, rapid disease progression, and poor survival. Despite the wide range of tx used during the study, including subsequent LOT, these results highlight the urgent need for new therapeutic options for this populationKeywords: Treatment, relapsed/refractory, Multiple myeloma, Clinical trial