P926: DARATUMUMAB, BORTEZOMIB AND DEXAMETHASONE FOR TREATMENT OF PATIENTS WITH RELAPSED OR REFRACTORY MULTIPLE MYELOMA AND SEVERE RENAL IMPAIRMENT: RESULTS FROM THE PHASE 2 GMMG-DANTE TRIAL
2022-06-01

Background: Renal function impairment is one of the main characteristics of multiple myeloma (MM) leading to diagnosis and defining treatment requirement in first-line and subsequent relapse. However, limited data exist on safety and efficacy of anti-MM regimens in patients (pts) with severe renal impairment and those requiring hemodialysis as pts are mostly excluded from clinical trials and specific trials in this indication are rare. Proteasome inhibitors as bortezomib (BTZ) are known to represent one of the preferable drug classes in patients with renal impairment due to rapid response, lack of dose adjustment and renoprotective effects. Daratumumab (DARA) is an anti-CD38 monoclonal antibody which enhances response rates and efficacy when added to standard of care regimens, both in newly diagnosed and relapsed and refractory (RR)MM. The combination of BTZ, dexamethasone (DEX), and DARA (DVd) has been shown to be efficacious and safe in RRMM in the phase 3 study CASTOR (Palumbo et al., NEJM 2016). In the CASTOR trial, pts with a GFR < 20 ml/min were excluded. Aims: Here, we present results from the primary analysis of the investigator-initiated multicenter GMMG-DANTE (NCT02977494) trial investigating DVd in RRMM pts with severe renal impairment including pts on hemodialysis. Methods: RRMM pts with measurable disease who had received at least 1 prior line of therapy and a GFR < 30 ml/min or undergoing hemodialysis were eligible. Pts received DVd in the approved schedule with 8 cycles (21 d/cycle) of BTZ (1.3 mg/m2, SC) on Days 1, 4, 8, and 11 and DEX (20 mg, PO or IV) on days 1, 2, 4, 5, 8, 9, 11, and 12 + DARA (16 mg/kg, IV) given weekly for cycles 1-3, Q3W for cycles 4-8, and Q4W thereafter. 36 patients were planned to be included into the trial. The trial was closed prematurely after 22 patients due to inferior recruitment. The primary endpoint was overall response rate (ORR). Key secondary endpoints were progression-free survival (PFS), overall survival (OS) and safety. Response assessment was performed using the IMWG criteria. Results: 22 pts from 6 German and one Greek site were included from 2017-2020. Analyzed population included 21 patients. Median age was 70 years. Median GFR was 21.0 ml/min, 8 patients were under hemodialysis. Median number of prior lines was 2 (range 1-10). All patients started DVd treatment. For one patient it was not possible to obtain a response. ORR was 67% (14/20) with 6 pts (29%) showing a partial response (PR), 6 pts (29%) a very good partial response (VGPR) and 2 pts (10%) a complete response (CR). Median treatment duration was 24 weeks (range 2-106). After a median follow-up of 28 months, median PFS was 10.4 months, median OS was not reached (OS after 24 months until 39 months plateau 0.504). The most frequent toxicity ≥ grade 3 was hematologic, with anemia in 23.8%, thrombocytopenia in 23.8% and neutropenia in 9.5%. Main non-hematologic adverse events (AEs) ≥ grade 3 were infections (23.8%) with mainly pneumonias. Polyneuropathy all grade was described in 52.4%. Summary/Conclusion: In this phase II prospective trial we demonstrated that DVd shows relevant efficacy in RRMM pts with severe renal impairment and can be safely administered. Efficacy is comparable to the one reported in patients with no severe renal impairment. Toxicity does not differ from previously reported data on DVd. Acknowledging the generally reported impaired outcome of MM pts showing severe renal impairment, PFS and OS underline the importance of effective MM regimens which can be safely administered in a difficult to treat population.