P-172: Daratumumab (Dara), Cyclophosphamide, Thalidomide and Dexamethasone: a quadruplet intensified treatment for transplant eligible newly diagnosed Multiple Myeloma (TE NDMM) patients final results

Background Newly drugs access for MM treatment still a challenge. One of the available inductions for TE NDMM patients (pts) worldwide is cyclophosphamide (C), thalidomide (T) and dexamethasone (d)- (CTd). We hypothesized that the Daratumumab and CTd combo could be safe and allow deeper activity as an alternative protocol. Primary endpoint was to evaluate the VGPR after two consolidation cycles post-ASCT. Secondary endpoints were the ORR during all treatment phases and MRD, based on the IMWG criteria that includes the NGF by the EuroFlow® and PET-CT and the safety profile Method This is a phase II, open-label single-center clinical trial. The main inclusion criteria were: TE NDMM, CrCl > 30 ml/min, normal cardiac, renal and liver function and the ECOG performance status = 0 - 2. The protocol was Dara-CTd for up to four 28-day induction cycles: C-500mg PO on days 1,8 and 15, T at 100-200mg PO on days 1 to 28, (d) at 40mg PO on days 1,8,15 and 22 and Dara at 16mg/Kg/dose IV- QW during cycles 1 - 2 and every other week in cycles 3 – 4, followed by ASCT. All pts received up to four 28-day consolidation cycles that was started at D+30 after ASCT: Dara and (d) at 40mg every other week, associated with T at 100mg PO on days 1 - 28. Dara was used monthly as maintenance until progression or limiting toxicity. G-CSF was used for stem cell (SC) mobilization and plerixafor if needed. All pts received anti(viral, pneumocystis and thrombotic) prophylaxis. Results 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 HR [del17p, t(4;14) or t(14;16)]. To date, all pts have completed induction, 19 have received transplant and 17 have completed D+90 post-transplant assessment. No SC mobilization failure was observed, and five (26%) pts needed plerixafor use. In an ITT analysis, after the end of induction (cycle 4), 19 (90%) of the pts obtained > PR and 8 (38%) obtained >VGPR, including three MRD negativity by NGF. 17 pts have completed two consolidation cycles after transplant and 94% obtained > VGPR, 12 (70%) obtained MRD negativity by NGF and nine (53%) had negative PET-CT. Seven (41%) pts had both flow and PET-CT negativity. Three pts died from infection, one before transplant because of Covid, one on post-transplant, considered not related to the investigational agent, and another after consolidation, related to the investigational agent. The most common nonhematological 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). Conclusion This is the first study that combined Dara with CTd as induction for TE NDMM pts. This present data has shown that the association of Dara-CTd achieved the primary end point once > 90% of the pts achieved VGPR after two consolidations cycles, and safety profile was acceptable. Clinical trial information NCT03792620.