Phase 2 trial of daratumumab, cyclophosphamide, thalidomide and dexamethasone in newly diagnosed multiple myeloma

• The quadruplet regimen Dara-CTD was active and safe as frontline therapy in ASCT-eligible newly diagnosed multiple myeloma.

• Dara-CTD may be an alternative to potentially more toxic and costly quadruplet regimens containing PIs and lenalidomide.

Anti-CD38 monoclonal antibodies have been successfully combined with immunomodulatory agents, proteasome inhibitors (PI), alkylators, and corticosteroids in newly diagnosed multiple myeloma (NDMM). We assessed a regimen of daratumumab, cyclophosphamide, thalidomide, and dexamethasone (Dara-CTD) in patients with NDMM eligible to autologous stem-cell transplantation (ASCT). Patients received four 28-day cycles of induction therapy with Dara-CTD followed by ASCT, four cycles of consolidation Dara-Td, and single-agent daratumumab maintenance until progression or limiting toxicity. The primary endpoint was the percentage of patients achieving at least a very good partial response (VGPR) after the second cycle of consolidation. A key secondary endpoint was progression-free survival (PFS). We enrolled 24 patients, with a median age of 59.5 years, 62.5% of whom were females. Patients received a median of 28 treatment cycles. The rate of VGPR or better was 75.0% (95% confidence interval, 68.3% to 98.7%); of 18 responding patients, three had a complete and 15 had a VGPR. The response duration varied between 9.5 and 41.9 months (median not reached). The estimated PFS rate at 36 months was 65%, and the overall survival rate at 48 months was 70%. The most frequent toxicity was constipation, febrile neutropenia, lymphopenia, neutropenia, peripheral neuropathy, and stomatitis. There were seven documented cases of coronavirus 2019 infection, two of which fatal. Two patients had permanent treatment discontinuation due to toxicity, one case each attributed to cyclophosphamide and daratumumab. Dara-CTD is an active, PI-free, quadruplet regimen with an acceptable safety profile for patients with ASCT-eligible NDMM. NCT03792620