(PA-472) PomCyDex in Relapsed/Refractory Multiple Myeloma: Impact of Prior Refractoriness in a Real-World Setting

Introduction:  Despite recent advances, outcomes for patients with relapsed/refractory multiple myeloma (RRMM) who have been exposed to proteasome inhibitors (PIs), immunomodulatory drugs (IMiDs), and anti-CD38 monoclonal antibodies (mAbs) remain poor. Identifying effective and tolerable regimens for this heavily pretreated population is a clinical priority. The combination of pomalidomide, cyclophosphamide, and dexamethasone (PomCyDex) has shown synergistic activity. However, evidence on its effectiveness and safety, especially in double- and triple-refractory patients, remains limited.

Methods:   We conducted a retrospective, multicenter study across 13 centers in Catalonia, Spain, including RRMM patients treated with PomCyDex after at least one prior therapy. Patients previously treated with pomalidomide or cyclophosphamide, lacking response data, or lost to follow-up were excluded. Treatment included pomalidomide 4 mg daily (days 1–21), cyclophosphamide 50 mg daily (days 1–21), and weekly dexamethasone. Responses were assessed per 2016 IMWG criteria. Refractoriness was defined as progression during or within 60 days of treatment. Primary endpoints were ORR, PFS, and OS. Statistical analyses used Kaplan-Meier, Cox models, and comparative tests; significance was p< 0.05. Adverse events were recorded per CTCAE v6.0.

Results:   The cohort included 177 patients with a median age of 72 years and a median of 3 prior therapy lines. Double-refractory (lenalidomide and PIs) patients comprised 89.2%, while 64.4% were triple-refractory including lenalidomide and anti-CD38 mAbs. The ORR was 60.5%, which was significantly lower in lenalidomide-refractory patients with prior responses under 12 months (32.7% vs. 67.3%, p< 0.001) and in patients with high-risk cytogenetics (45.7% vs. 66.7%, p=0.03). Median PFS was 7 months overall, with responders achieving ≥PR showing longer PFS (10 vs. 2 months, p< 0.01). Median OS was 13 months, poorer among patients with high-risk cytogenetics, prior lenalidomide refractoriness, or failure to respond to PomCyDex. In multivariate analysis, achievement of ≥PR (HR 0.11, 95% CI 0.52–0.24, p< 0.01) and prior anti-CD38 response < 12 months (HR 1.4, 95% CI 1.06–1.9, p=0.02) were independent predictors of PFS, while response to PomCyDex (HR 0.25, 95% CI 0.13–0.46, p< 0.01) was the main predictor of OS. Grade ≥3 AEs included: neutropenia (57.6%), thrombocytopenia (29%), anemia (27.7%), and infections (29.4%). Dose reductions were required in 45.8%, and 12.9% discontinued due to AEs.

Conclusions:   PomCyDex showed manageable safety in heavily pretreated RRMM patients. Outcomes were determined by the duration of prior response to lenalidomide or anti-CD38 mAb treatments and by achieving at least a PR. PomCyDex is a treatment option for double- and triple-refractory RRMM patients, especially those with longer prior responses.