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Combination Daratumumab and Dexamethasone Shows Promising Efficacy in Patients with RRMM and Severe Renal Impairment
Among patients with relapsed/refractory multiple myeloma (RRMM) and severe renal impairment (RI) or on dialysis, daratumumab plus dexamethasone showed promising efficacy with manageable safety; these data were presented at the 63rd American Society of Hematology Annual Meeting following the final analysis of the phase 2 DARE study.
“Despite the availability of novel agents in treating multiple myeloma (MM), renal impairment (RI) remains a poor prognostic factor, and the median survival of patients with MM and RI is approximately half of that for MM pts with normal renal function. RI can affect up to 50% of pts with MM at presentation, highlighting the need for effective treatment options for this patient population,” explained Efstathios Kastritis, MD, Department of Clinical Therapeutics, National and Kapodistrian University of Athens, School of Medicine, Greece, and colleagues.
With this in mind, researchers conducted DARE: a prospective, open-label, phase 2 study to assess the safety and efficacy of daratumumab with dexamethasone in patients with RRMM and severe RI or requiring hemodialysis.
DARE included adult patients across eight sites in Greece and Italy with documented RRMM and severe RI or who required hemodialyses and ≥2 prior lines of therapy (including bortezomib- and lenalidomide-based regimens), progressive disease by International Myeloma Working Group (IMWG) criteria, and an ECOG performance status score ≤2. Patients with prior anti-CD38 antibody treatment, including daratumumab, were not eligible.
Patients received 28-day treatment cycles with 16 mg/kg intravenous daratumumab (weekly for cycles 1-2, every 2 weeks for cycles 3-6, and every 4 weeks thereafter) and oral dexamethasone (40mg weekly, each cycle).
The primary end point was progression-free survival (PFS), secondary endpoints were overall response rate (ORR), renal response rate (RRR), and the safety of daratumumab assessed by IMWG criteria.
A total of 38 patients were enrolled, 37 of whom had ECOG PS ≤1 and 34 (89.5%) were at International Staging System (ISS) stage III; by revised ISS, 20 (52.6%) and 16 (42.1%) pts were at stages II and III, respectively. The median (range) prior systemic therapies was 3 (2-6), and 13 (34.2%) patients had undergone previous autologous stem cell transplantation. Additionally, the median eGFR at baseline was 13.0 mL/min/1.73m2, and 17 (44.7%) were on dialysis.
Furthermore, the median number of cycles given was 8.0 (1.0-38.0) and the median follow-up was 11.3 (<0.1–36.0) months. The median PFS was 11.8% (95% CI, 2.8-20.9 months), whole the ORR was 47.4%, with 13 (34.2%) patients achieving a very good partial response (VGPR) and 5 (13.2%) a partial response (PR). In dialysis patients, the ORR was 47.1% with 5 (29.4%) and 3 (17.6%) patients achieving VGPR and PR, respectively.
Additional results included the median time to first response, which was 0.9 (95% CI; 0.9–9.6) months). The RRR was 18.4% (5.9% for dialysis patients and 28.6% for non-dialysis patients), while the median OS and DOR (≥PR) were 24.5 (5.5-NR) months and 28.4 (95% CI; 15.1-NR) months, respectively. Among patients on dialysis, the median OS was 12.5 (95% CI; 2.2-NR), while the median OS for patients not on dialysis was not reached (95% CI; 10.1-NR0). The median (95%CI) DOR for patients dialysis and non-dialysis patients was not reached (15.1-NR) and 28.4 (3.5-NR) months, respectively.
Overall, half of the patients experienced ≥1 grade 3/4 adverse event (AE), while 10 (26.3%) had ≥1 serious AE (SAE), The most common grade 3/4 AEs were: anemia, hyperglycemia, and hypercalcemia. The most common SAE was septic shock.
“The administration of daratumumab with dexamethasone in pts with RRMM and severe RI or requiring hemodialysis is safe and effective therapy associated with a median PFS of approximately 12 months,” concluded Dr Kastritis et al.—Alexandra Graziano
Kastritis E, Terpos E, Symeonidis A, et al. Efficacy and Safety of Daratumumab with Dexamethasone in Patients with Relapsed/Refractory Multiple Myeloma and Severe Renal Impairment or on Dialysis: Final Analysis of the Phase 2 Dare Study. Presented at: the 63rd ASH Annual Meeting and Exposition; December 11-14, 2021; Atlanta, GA. Abstract 2729
