EVALUATION OF DARATUMUMAB, BORTEZOMIB, LENALIDOMIDE, AND DEXAMETHASONE (D-VRD) INDUCTION FOLLOWED BY DARATUMUMAB AND LENALIDOMIDE (DR) MAINTENANCE IN TRANSPLANT-ELIGIBLE MULTIPLE MYELOMA PATIENTS IN BRAZIL

The advent of novel therapeutic agents has markedly improved outcomes for patients with multiple myeloma (MM). The phase 2 GRIFFIN and phase 3 PERSEUS studies have demonstrated that adding daratumumab to VRD induction and consolidation therapy, as well as to lenalidomide maintenance therapy, significantly enhanced the depth of response and extended progression-free survival. This study evaluates the real-world experience with a quadruple induction regimen (D-VRD) followed by autologous stem cell transplantation (ASCT), and daratumumab plus lenalidomide (DR) maintenance as first-line treatment for transplant-eligible newly diagnosed multiple myeloma (TE-NDMM) patients in Brazil. We conducted a retrospective study involving TE-NDMM patients who received D-VRD induction therapy between January 2021 and June 2024. Descriptive statistics were used to summarize patient demographics, disease characteristics, response rates, and clinical outcomes. A swimmer plot was utilized to visualize patient timelines, treatment duration, and efficacy. Between April 2021 and June 2024, 18 patients received D-VRD induction. The median age was 60 years (range, 36-73), 67% were female, 78% were White and, 22% Black. At diagnosis, 44% had an ECOG PS score of 0 to 1, 67% had ISS stage I, 22% stage II, and 11% stage III. Clinical characteristics included 39% with hemoglobin < 10 g/dL and 78% with lytic bone lesions; none had creatinine levels > 2 mg/dL. The MM IgG isotype was present in 83% of patients. Cytogenetic abnormalities by FISH were evaluable in 3 patients The analysis was conducted at a median follow-up of 21 months (range, 4-38), with 17 patients receiving at least 4 cycles of D-VRD. The overall response rate (ORR) was 100%, with 71% achieving a complete response (CR) or better, 23% a very good partial response (VGPR), and 6% a partial response (PR). There were no cases of primary refractory disease, progressive disease, or relapse. One patient in CR died due to COVID-19. Regarding maintenance, 83% started DR; however, 1 patient suspended daratumumab due to skin reaction, and 2 suspended lenalidomide due to diarrhea and neutropenia. We compared the evolution of responses obtained after transplantation/consolidation with the responses after maintenance in 16 patients. Post-ASCT, the ORR was 100%, with 31% CR, 50% VGPR, and 19% PR. Responses continued to deepen over maintenance: among patients with VGPR post-transplant, 63% evolved to CR, and 37% maintained VGPR; among patients with PR, 33% achieved CR, 33% VGPR, and 33% continued in PR. The D-VRD induction therapy followed by DR maintenance demonstrated high efficacy, achieving a 100% ORR with 94% of patients achieving a VGPR or better in our cohort. These high response rates support the use of this treatment regimen for TE-NDMM patients in Brazil and highlight its potential as an effective first-line therapy in real-world settings.