DARA-VD VERSUS DARA-RD AS SALVAGE THERAPY FOR PATIENTS WITH MYELOMA. INITIAL FOLLOW-UP OF AN ITALIAN MULTICENTER RETROSPECTIVE CLINICAL EXPERIENCE BY RETE EMATOLOGICA PUGLIESE

Background: Daratumumab is a CD38 monoclonal antibody approved in monotherapy or in combination with bortezomib and dexamethasone (Dara-Vd) or lenalidomide and dexamethasone (Dara-Rd) for the treatment of relapsed or refractory myeloma (rrMM). Aims: We report here an initial multicenter retrospective analysis of 126 consecutive patients with rrMM treated with daratumumab in combination with bortezomib or lenalidomide as salvage therapy at 9 haematological centers in Puglia, conducted to evaluate the outcomes, as well as the toxicity profile of these combination in a daily practice setting outside clinical trials. Methods: Of 126 patients, 122 were evaluable for response and toxicity. Forty-two patients (33%) (15 F and 27 M) received Dara-Vd and 84 patients (67%) (41 F and 43 M) with Dara-Rd; 74% of them had relapsed MM and 26% MM refractory to one or more previous treatment lines. The median age at diagnosis was 62 years (range 36-77) in the Vd-group, 66 years (range 32-83) in the Rd-group. The median time to initiation of daratumumab from diagnosis was 5 years (range 3-9) in the Vd-group, 3 years (range 1-10) in the Rd-group. Patients had received a median 2 prior lines of therapy (range 1-6) in the Vd-group, a median 1 prior course of therapy (range 1-4) in the Rd-group. Twenty patients (48%) in the Vd-group and 30 patients (37%) in the Rd-group had previously undergone single or tandem ASCT. In the Vd-group all patients were previously exposed to at least one proteasome inhibitor (91% of patients to bortezomib, 37% of patients to carfilzomib), in the Rd-group only 18% of patients was exposed to lenalidomide. Results: The median number of administered cycles was 9 (range 1-23) in the VD-group and 8.5 (range 1-23) in the Rd-group. The ORR was 68.2% in the Vd-group (CR 4.8%, VGPR 12.2%, PR 51.2%) and 81.5% in the Rd-group (CR 21%, VGPR 35.8%, pr 24.7%). Median TTR was 2 months (range 1-6) in the Vd-group and 1.5 months (range 1-5) in the Rd-group. Median PFS was 10 months (range 8-16; 95% > CI) in the Vd-group; median PFS was not reached in the Rd-group (fig.1). Grade 3/4 neutropenia (37%) was the most common adverse event in the Rd-group, grade 3/4 thrombocytopenia (24%) was the most common adverse event in the Vd-group. Seventeen (41%) patients in the Vd-group discontinued treatment due to relapse, 16 patients (19%) in the Rd-group because of haematological toxicity (4.5%), relapse (7.5%), death (6%) and the development of urological cancer (1%). Summary/Conclusion: A higher rate of ORR (81.5% vs 68.2%) and very good partial response or better (responses > VGPR 56.8% vs 17%) was observed in the Dara-Rd group compared to Dara-Vd group. This difference could be due to the fact that: 1) in the Dara- Rd group the patients had received a lower number of prior antimyeloma therapies compared to Dara-Vd group; 2) the patients in the Dara-Rd group had a more indolent myeloma (median ISS 1) compared to the patients in the Dara-Vd group, who had a more advanced disease (median ISS 3); 3) in the Rd-group only 18% of patients was exposed to lenalidomide, in the Vd-group all patients were previously exposed to at least one proteasome inhibitor. Unfortunately, the interference of daratumumab with immunofixation and serum protein electrophoresis assays may lead to underestimation of CR.