Objective: Patients (pts) with multiple myeloma (MM) and severe renal impairment (RI) have poorer overall survival. Daratumumab (DARA), an IgG1κ human monoclonal antibody that targets CD38, has shown efficacy and a favorable safety profile in pts with relapsed or refractory MM (RRMM). Moreover, in population pharmacokinetic analyses, no clinically important differences in exposure to DARA were observed between pts with MM and RI regardless of renal function. The aim of the DARE study [NCT03450057] was to assess the safety and efficacy of DARA in pts with RRMM and severe RI or requiring hemodialysis.
Methodology: DARE is a prospective, open-label, multicenter, phase 2 study, which included pts with documented RRMM and severe RI (eGFR<30ml/min/1.73m2) or requiring hemodialysis. Participating pts must have ≥2 lines of therapy with both bortezomib- and lenalidomide-based regimens and an Eastern Cooperative Oncology Group performance status (ECOG PS) score ≤2. Exclusion criteria include previous DARA or other anti-CD38 therapy exposure. Pts receive 28-day treatment cycles with 16mg/kg intravenous DARA (weekly for cycles 1–2, every 2 weeks [wks] for cycles 3–6, and every 4 wks thereafter) and oral dexamethasone (40mg weekly, each cycle). The primary endpoint is progression-free survival (PFS). Secondary endpoints are overall response rate (ORR; proportion of pts with partial response or better), renal response rate (RRR; proportion of pts with best response of renal partial response or better), and safety. All responses are based on investigators’ assessment per International Myeloma Working Group criteria.
Results: Thirty-eight pts with obtained informed consent, enrolled in 7 centers, were included in this analysis. The pts median age was 72 years, and most were male (75%). At study initiation 7% and 93% of pts had International Staging System (ISS) stage II and III disease, respectively; 51% and 49% of pts had revised ISS stage II and III, respectively. At baseline, the median time from MM diagnosis was 4.2 years; 24%, 72%, and 4% pts had ECOG PS 0, 1, and 2, respectively; the median eGFR was 13.0mL/min/1.73m2. Median number of prior lines of therapy was 3, and 35% pts had previous autologous stem cell transplantation. The median number of therapy cycles received per patient was 7.0. The median follow-up was 8 months and the 6-month PFS rate was 51%. The ORR was 41% (including VGPR in 29% of pts). The RRR was 22%. The median time from first DARA dose to first partial response or better was 1.5 months. Of all grade 3 or 4 AEs, the most frequent were anemia (21%), thrombocytopenia (13%), hyperkalemia (11%), and hyperglycemia (8%).
Conclusion: DARA plus dexamethasone was efficacious with a favorable safety profile in pts with RRMM and severe RI or requiring dialysis. Hematologic responses were high in these heavily pretreated pts, while more than one-fifth of them also achieved a renal response.
