KEY TAKEAWAYS
- LocoMMotion (NCT04035226) is a prospective observational study that evaluated SOC regimens for TCE patients with relapsed/refractory multiple myeloma.
- The study’s primary aim was to assess the efficacy and safety of real-world SOC regimens for TCE patients with RRMM.
- The final analysis of the LocoMMotion study demonstrates the limited efficacy of standard-of-care regimens for TCE patients with RRMM.
LocoMMotion (NCT04035226) is the first prospective observational study to evaluate the efficacy and safety of real-world standard of care (SOC) regimens for triple-class exposed (TCE) patients 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). In this study, the researchers reported the final results with an extended median study follow-up and subsequent lines of therapy (LOT) information.
TCE patients (18 years) with MM who were double-refractory to a PI and IMiD or had 3 prior LOT were enrolled after providing informed consent. Patients had documented progressive disease (PD) since the last LOT and EasternCooperative Oncology Group performance status 1. Pt-level data and choice of tx (index LOT [i.e., first tx upon study enrollment; only approved therapies] and subsequent LOT [experimental tx allowed]) were collected for 24mo after the first index LOT dosing of the last pt enrolled. RRC evaluated responses according to International MyelomaWorking Group response criteria. The primary effectiveness endpoint was ORR. Additional efficacy endpoints and safety were secondary endpoints. Using descriptive statistics, variables were summed up. ORR was reported with 95% Clopper-Pearson (precise) confidence intervals. Using Kaplan-Meier methodologies, time-to-event data were summarised.
The study ran from August 2019 to October 2022, with a median follow-up of 26,4 months (95% CI: 25.0–28.2). There were 248 individuals with a median age of 68 years (range: 41–89), and 135 (54.4%) were male. At baseline, patients had received a median of 4 prior LOT (range 2–13), 182 (73.4%) were triple-class refractory, 229 (92.3%) were refractory to the last primary LOT, and 160 (64.5%) patients had received a stem cell transplant (SCT) previously. 91 distinct tx regimens were used in the index LOT, 162 (65.3%) patients had 3 drugs, and 6 (2.4%) patients had SCT. The median duration of treatment (mDOT) ranged from 0.1 to 33.6 months. ORR was 31.9% (95%CI: 26.1–38.0%); median duration of response was 7.4 months (95%CI: 4.9–11.1%); mPFS and mOS were 4.6 months (CI: 3.9–5.6) and 13.8 months (CI: 10.8–17.0), respectively. Twelve- and twenty-four-month PFS rates were 21.0% (95%CI: 15.3–27.3) and 10.5% (95%CI: 6.1–16.3), respectively. The 12-month and 24-month OS rates were 53.4% (95%CI 46.7–59.6) and 33.7% (95%CI 27.3–40), respectively. 152 pcs (61.3%) had subsequent LOT (1 next LOT only n=78; ≥2 subsequent LOT n=74; mPFS2 (from the beginning of the study to the succeeding LOT1) was 10.8 months (95% CI: 8.4–13.0).
In subsequent LOT1 with mDOT 2.8 months (range: 0–29.7), 79 distinct regimens were utilized. Utilization of BCMA-targeted therapy increased from 2.8% in the index LOT to 24.2% in the subsequent LOT. During the index LOT, 86.7% of patients experienced an adverse event (AE), with cytopenias being the most common; 13.2% of patients developed a second primary malignancy (index LOT n=5; after index LOT n=8). During the study, 158 pts (63.7%) perished; 67.7% of deaths were due to PD, and 15.8% were due to AEs.
The final analysis (median study follow-up >2 years) of the first prospective study of real-world therapy for TCE patients with RRMM revealed an absence of well-established SOC, rapid disease progression, and poor prognosis. Despite the wide variety of treatments used during the study, including subsequent LOT, these results demonstrated the critical need for novel therapeutic options for this population.
Clinical Trial: https://clinicaltrials.gov/ct2/show/NCT04035226
Philippe Moreau, Katja Weisel, Valerio De Stefano, Hartmut Goldschmidt, Michel Delforge, Mohamad Mohty, Joanne Lindsey-Hill, Dominik Dytfeld, Emanuele Angelucci, Laure Vincent, Aurore Perrot, Reuben Benjamin, Niels W.C.J. van de Donk, Enrique Ocio, Ester in ‘t Groen-Damen, Tito Roccia, Jordan Schecter, Imene Haddad, Vadim Strulev, Lada Mitchell, Jozefien Buyze, Silva Saarinen, Octavio Costa Filho, Hermann Einsele, Maria-Victoria Mateos/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/Inc, M. G. (n.d.). LOCOMMOTION: A PROSPECTIVE, OBSERVATIONAL, MULTINATIONAL STUDY OF… by Prof. Philippe Moreau. Library.ehaweb.org. Retrieved July 18, 2023, from https://library.ehaweb.org/eha/2023/eha2023-congress/386733/philippe.moreau.locommotion.a.prospective.observational.multinational.study.of.html?f=menu%3D16%2Abrowseby%3D8%2Asortby%3D2%2Ace_id%3D2489%2Aot_id%3D27922%2Atrend%3D4016%2Amarker%3D4178
