Session: 653. Myeloma and Plasma Cell Dyscrasias: Prospective Therapeutic Trials: Poster I
Hematology Disease Topics & Pathways:
Biological therapies, Antibody Therapy, Plasma Cell Disorders, Diseases, Therapies, Immunotherapy, Lymphoid Malignancies, Monoclonal Antibody Therapy
Methods: This phase 2 trial (NCT03713294) enrolled pts with RRMM who had disease progression and were refractory to Dara. Key eligibility criteria included: measurable disease as per IMWG criteria, at least one prior line of therapy, adequate marrow/organ function (neutrophil count ≥1.0 x 109, platelets ≥50x 109, creatinine clearance ≥30 mL/min), ECOG performance status ≤2, and disease not refractory to Pom. EPd was dosed as per the ELOQUENT 3 study. The trial utilized a two–stage design with an interim analysis to test the null hypothesis that the true overall response rate (ORR) in this patient population is most 20% vs. the alternative hypothesis that it is at least 40%, with 90% power and 9% type I error. Treatment was given until disease progression, intolerance, or patient refusal.
Results: 37 pts were enrolled. Median follow-up time was 23.4 months (95% CI: 14.6-37.2). The median age was 70 years (range: 42-84), 12 (32.4%) pts had ISS III disease and 16 (43.2%) pts had high risk cytogenetics. Pts had received a median of 4 (range: 1-9) prior lines of therapy. Prior anti-MM agents included bortezomib (35; 94.6%), Len (34; 91.9%), carfilzomib (9; 24.3%), ixazomib (9; 24.3%), stem cell transplantation (18; 48.6%) and CAR-T cell therapy (1; 2.7%). The majority of pts (33; 89%) were previously exposed to both a proteasome inhibitor and Len. 25 (67.6%) pts got Dara-based therapy as the immediate line of therapy prior to EPd (after a median of 4 prior lines [range 1-7]) whereas 12 (32%) pts got Dara-based therapy ≥1 line prior to EPd (after a median of 6 prior lines [range 2-9]). ORR in all pts was 35.1% (13 pts), with no CRs, 1 (2.7%) VGPR, and 12 (32.4%) PRs. Four pts (10.8%) achieved an MR and 15 (40.5%) achieved SD. The study met its primary endpoint. The ORR in pts exposed to Len was 11/34 (32.4%) compared to 2/3 (66.7%) in patients not exposed to Len. The ORR in pts with Dara as the immediate prior line of therapy was 44% (11/25) compared to 16.7% (2/12) in pts who had received Dara-based therapy ≥1 line prior to EPd (p=0.15). The median PFS for the entire cohort was 3.7 mth (95% CI: 2.9-11.1) (Figure 1A). The median time to best response was 2.9 mth. The median time to next treatment was 8.5 mth (95% CI: 6.8-20.4). Median PFS of pts with Dara as the immediate prior line of therapy was 4.7 mth (95% CI: 3.2-19.6) compared to 2.8 mth (95% CI: 2.0-NA) in patients who had received Dara-based therapy ≥1 line prior to EPd (p=0.03; Figure 1B). The most common grade 3/4 adverse events were neutropenia (57%), anemia (22%), thrombocytopenia (16%), leucopenia (16%), and fatigue (8%).
Conclusion: This was a positive study with EPd showing clinically meaningful benefit in pts with Dara-refractory RRMM. The reported PFS of 3.7 mths is less than the 10.3 mths reported in ELOQUENT 3 trial which suggests that Elo-based regimens are less effective in Dara-refractory pts. Interestingly, pts had a significantly superior PFS if they received EPd immediately following progression on Dara, however they were less heavily pretreated comparted to pts who got EPd ≥1 line after Dara failure. Nonetheless, EPd is an effective regimen in the post-Dara setting.
Disclosures: Ailawadhi: GSK, Sanofi, BMS, Takeda, Beigene, Pharmacyclics, Amgen, Janssen: Consultancy.
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