PB1997: DARATUMUMAB, LENALIDOMIDE, BORTEZOMIB, AND DEXAMETHASONE FOR TRANSPLANT-ELIGIBLE NEWLY DIAGNOSED MULTIPLE MYELOMA: OUTCOME AND SAFETY PROFILE FROM A REAL-WORLD SINGLE CENTER EXPERIENCE

Abstract

Background: lenalidomide, bortezomib, and dexamethasone (RVd) followed by autologous stem cell transplant is standard frontline therapy for transplant eligible newly diagnosed multiple myeloma (MM).The addition of daratumumab (D) to RVd improve the depth of response (Stringent complete remission and MRD negativity). RVd-D combination is now being suggested as first-line treatment. Real-word data is lacking. Aims: We aim to share our experience regarding clinical response and safety profile of D-RVd for treatment of newly diagnosed transplantation eligible MM patients. Methods: We conducted a retrospective study with medical review of all patients diagnosed with multiple myeloma and treated with D-RVd at The National Center for Cancer Care and Research (NCCCR) in Qatar between January 2019 to December 2021. Overall response rate and safety profile were evaluated. All analyses were descriptive and exploratory in nature. Results: Fifteen newly diagnosed MM patients had received D-RVd in the time period of the study. The median age of patients was 58 year (range, 36-68 years) and the majority 12 (80 %) were male. The immunoglobulin (Ig) subtypes were IgG 9 (60%), IgA 3 (20%), free light chain 3 (20%). At diagnosis, 14 patients had bone lesions and 4 had extramedullary plasmacytoma. Anemia, hypercalcemia (serum calcium > 2.6 mmol/L) and/or renal impairment (serum creatinine > 133µmol/L) was present in 66%, 66% and 33% of patients respectively. Bone marrow plasmacytosis more than 60% on bone marrow examination was reported in 11/14 (78%) of patients. The proportion of patients at ISS stage I, II, and III were 1 (7%), 6 (40%), 8 (53%) respectively. Cytogenetic abnormalities detected via karyotyping and/or FISH were present in 9 of 12 evaluated patients. The average number of D-RVd were 4 cycles. The overall response rate (ORR) post induction therapy was evaluated in 14 patients (one patient was not evaluated for response due to early death), 9 (64%) patients had a complete response (CR), 4(29%) had very good partial response (VGPR) and one had partial response (PR). No myeloma progression while receiving induction therapy occurred. So far, seven patients have undergone autologous stem cell transplant. Median CD 34+ cell yield was 5,2 million cells per kg body weight, plerixafor were used in 5 patients and 5 patients required more than one apheresis session. Survival data to be collected and reported after a longer follow up period. The most common adverse events (AEs) were hematological toxicities; grade 3/4 neutropenia was detected in 6 patients (40%), thrombocytopenia in 3 patients (20%), lymphopenia in 4 patients (27%) and leukopenia in 2 patients (13%). Infusion reactions occurred in 2 patients (13%), one of them experienced anaphylactoid reaction that required infusion interruption. Non-hematological AEs where uncommon and included grade 2 hepatotoxicity in one patient and venous thrombosis in one patient. None of the AEs lead to treatment discontinuation. One death occurred early during the second cycle due to streptococcus pneumoniae meningitis. Image:Summary/Conclusion: Our real-world results show a high response rate (CR/VGPR) to D-RVd as first-line treatment in transplantation eligible patients with MM. However, the feasibility and safety of this treatment regimen needs to be confirmed in larger prospective studies.