Ranking importance of prognostic factors for relapsed/refractory multiple myeloma (RRMM): international physician panel consensus following a systematic review of the literature

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. 43.3months, 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.