Professor of Medicine/Consultant Mayo Clinic, Rochester, MN, US Rochester, Minnesota, United States
Introduction: The introduction of anti-CD38 antibodies (daratumumab) in the treatment landscape of multiple myeloma (MM) has increased the outcomes of patients with relapsed disease in recent years. However, the ideal combination of these drugs (Dara-IMiD vs. Dara-PI) in patients with relapsed MM is unclear.
Methods: We reviewed MM patients treated with daratumumab as second-line therapy at our institution from January 1st, 2016, to June 31st, 2022, to assess the outcomes with the different combination therapies. We used the Kaplan-Meier method to estimate PFS from the first relapse.
Results: We identified 404 patients with a median age of 63.6 years (range: 27.1 – 90.4). Most patients received triplet induction therapy (94%) and upfront transplant (69%) as primary therapy. At the time of Dara initiation, 40% were refractory to IMiDs, 23% to PIs, 19% to both, and 19% to neither drug. Patients treated with Dara-IMiD had significantly better PFS than Dara-PI (28.7 months vs. 13.5 months, p< 0.01, respectively). When stratifying patients based on FISH classification, we found that both high-risk patients (25.3 vs. 8.1 months, p=0.01, respectively) and standard-risk patients (45.5 vs. 17 months, p< 0.01, respectively) benefited significantly from the Dara-IMiD regimen. Among patients treated with Dara-IMiD, those already refractory to IMiDs from the first line had significantly shorter PFS than those without IMiD resistance (14.6 vs. 43.3 months, p< 0.01, respectively). In addition, the lenalidomide-based combination resulted in significantly better PFS compared to pomalidomide in our cohort (39.4 vs. 22.4 months, p< 0.01, respectively). However, no difference was found in the IMiD refractory population (14.2 vs. 17.8 months, respectively). Finally, no significant differences were seen between Dara-IMiD and Dara-PI in patients only refractory to IMiD (16.2 vs. 12.8 months, p=NS, respectively).
Conclusions: While further studies are required to adjudicate the best combination, we conclude that Dara-IMiD might be more effective in patients with relapsed MM, especially for patients not refractory to IMiDs at first relapse.
