Newly drugs access for MM treatment still a challenge in some countries. One of the most availableinductions for TE NDMM patients (pts) worldwide is cyclophosphamide (C), thalidomide (T) and dexamethasone (d)-(CTd). Dara the first anti- CD38, had been combined with VCd, VTd and VRd and markedly increased the depth andduration of the response. We hypothesized that the combination of Dara and CTd could be safe and allow deeper activityas an alternative protocol.

The primary endpoint was to evaluate the VGPR after two consolidation cycles post-autologousstem cell transplantation (ASCT). Secondary endpoints were the overall response rate during alltreatment phases and minimal residual disease (MRD), based on the International Myeloma WorkingGroup (IMWG) criteria that includes the next-generation flow (NGF) by the EuroFlow®and PET-CTand the safety profile.

This is a phase II, open-label single-center clinical trial. The main inclusion criteria were: TENDMM, creatinine clearance > 30 mL/min, normal cardiac, renal and liver function and the EasterCooperative Oncology Group (ECOG) performance status = 0 - 2. The protocol was Dara-CTd for upto four 28-day induction cycles: C-500 mg oral (PO) on days 1,8 and 15, T at 100-200 mg PO on days1 to 28, (d) at 40 mg PO on days 1,8,15 and 22 and Dara at 16 mg/kg/dose intravenous (IV) on days1,8,15 and 22 during cycles 1 - 2 and every other week in cycles 3 – 4, followed by ASCT. All ptsreceived up to four 28-day consolidation cycles that was started at D+30 after ASCT: Dara at 16 mg/kg and (d) at 40 mg every other week, associated with T at 100 mg PO on days 1 - 28. Dara at 16 mg/kg was used monthly as maintenance until progression or limiting toxicity. G-CSF was used forstem cell (SC) mobilization and plerixafor had been allowed whenever the pts need. All pts receivedantiviral, anti-pneumocystis and anti-thrombotic prophylaxis.

The first pts was enrolled in November 2018. A total of 21 pts were included, the median age being 56 (range 37– 67 years), 19 (90%) were non-white, 3 (14%) had an R-ISS = 1, 12 (57%) had an R-ISS = 2 and 3 (14%), an R-ISS = 3. Five (24%) pts had high-risk chromosomal abnormalities [del17p, t(4;14) or t(14;16)]. To date, all pts have completedinduction, 19 have received transplant and 17 have completed D+90 post-transplant assessment. No SC mobilizationfailure was observed, and five (26%) pts needed plerixafor use. In an intention to treatment analysis, after the end ofinduction (cycle 4), 19 (90%) of the pts obtained > PR and 8 (38%) obtained >VGPR, including three MRD negativity byNGF. 17 pts have completed two consolidation cycles after transplant and 94% obtained > VGPR as best response, 12(70%) obtained MRD negativity by NGF and nine (53%) had negative PET-CT. Seven (41%) pts had both flow and PETCTnegativity. Three pts died from infection, one before transplant because of Covid infection, on post-transplant, considered not related to the investigational agent, and another after consolidation, related to the investigational agent. The most common nonhematological adverse events (AEs) grades 3 and 4 before ASCT were neuropathy (n = 6), infusion reaction (n = 7), infection (n = 2), hypertension (n = 1) and rash (n = 1).

This is the first study that combined Dara with CTd as induction for TE NDMM pts. This presentdata has shown that the association of Dara-CTd achieved the primary end point once > 90% of the pts achieved VGPRafter two consolidations cycles, and safety profile was acceptable.

NCT03792620.