P-409: Real-Life Outcomes in Triple-Class Exposed (TCE) Relapsed/Refractory Multiple Myeloma (RRMM) Treated With Carfilzomib- and/or Pomalidomide-Based Regimens in the LocoMMotion and MoMMent Studies

Introduction: A pooled analysis from the prospective, non-interventional, multinational LocoMMotion (NCT04035226) and MoMMent (NCT05160584) studies demonstrated suboptimal outcomes in patients (pts) with TCE RRMM. The results also highlighted the lack of a single standard of care (SOC), with more than 100 different regimens used. The current analysis evaluates outcomes in pts from LocoMMotion and MoMMent treated with carfilzomib- or pomalidomide-based regimens as observed during the period from 2019–2022, preceding the era of CAR-T cell therapies and bispecific antibodies.

Methods: Data were pooled from LocoMMotion (clinical cut-off [CCO]: Oct 27, 2022; final data) and MoMMent (CCO: Aug 18, 2023). Both studies have similar designs. Eligible pts received ≥3 prior lines of therapy (LOT; LocoMMotion allowed < 3 prior LOT if pts were double refractory to a PI and IMiD), were TCE, had measurable disease and documented progressive disease since their last LOT, and had an ECOG performance status (PS) score of 0 or 1 at screening. All pts provided informed consent. The primary endpoint was overall response rate (ORR), evaluated per IMWG criteria by the same review committee in both studies. Continuous variables were summarized using descriptive statistics, and ORR was reported with 95% exact CIs. Time-to-event data were summarized by Kaplan-Meier methods.

Results: The current pooled analysis includes 166 pts (LocoMMotion, n=131; MoMMent, n=35) treated with either a carfilzomib- or pomalidomide-based regimen. Median follow-up was 24.4 mo (range, 18.2–27.9). At baseline, median age was 69 years, 56.6% of pts were male, 74.7% had an ECOG PS of 1, and median time since diagnosis was 6.0 years. Pts received a median of 4 prior LOT (range, 2–12), 72.9% were triple-class refractory, and 11.4% were penta-drug refractory. 20 pts (12%) were refractory to both carfilzomib and pomalidomide. Overall, 36 unique carfilzomib- or pomalidomide-based regimens were used as SOC. The most common (≥5% of pts) were cyclophosphamide, pomalidomide, and dexamethasone (24.7%); carfilzomib + dexamethasone (20.5%); pomalidomide + dexamethasone (12.7%); and elotuzumab, pomalidomide, and dexamethasone (5.4%). ORR was 34.3% (95% CI, 27.2–42.1), median duration of response was 8.1 mo (95% CI, 5.2–11.1), median progression-free survival was 5.5 mo (95% CI, 4.4–6.0), median time to next treatment was 6.2 mo (95% CI, 5.3–7.2), and median overall survival was 15.3 mo (95% CI, 13.0–21.5).

Conclusions: These results suggest that outcomes in pts with TCE RRMM remain poor despite the use of carfilzomib and pomalidomide. New therapies, such as CAR-T cell therapies and bispecific antibodies, are needed to address the remaining high unmet need for patients with TCE RRMM.