Daratumumab after Allogeneic Hematopoietic Stem Cell Transplantation in Multiple Myeloma: Safety and Efficacy. a Retrospective Study from the Cmwp EBMT

BACKGROUND Allogeneic stem cell transplantation (allo-HSCT) is a treatment option for high-risk multiple myeloma (MM), especially in patients who relapse early following auto-HSCT. Though there is a proven graft versus myeloma effect, relapse remains common. Daratumumab (Dara) is a humanized monoclonal anti-CD38 antibody approved for both newly diagnosed and relapsed MM. Its mechanisms of action include direct anti-MM activity (CDC, ADCC, ADCP, apoptosis induction) and indirect anti-MM activity depleting CD38+ immunosuppressive regulatory cellsand promoting T-cell expansion and activation. The combination of its mechanism of action and lack of toxicity makes Dara a good candidate for use in the post-allo-HSCT setting. However, its immune effects (decrease in CD38-positive immune suppressor cells, including Tregs, NK cells, regulatory B cells, and myeloid-derived suppressor cells) may interfere with post-allo anti-MM effects. Nikolaenko et al (Clin Lymph Myeloma Leuk 2020) reported that aGVHD developed in five (15%) of 34 patients given Dara (mostly in combination) as treatment for post-allo relapse and the median PFS was 4.5 months. METHODS We performed a retrospective study to evaluate the safety and efficacy of Dara post-allo-HSCT). Patients with MM having received at least one Dara infusion at any time after allo-HSCT were included. Key exclusion criteria were plasma cell leukemia and AL amyloidosis. RESULTS A total of 121 patients who received Dara after a first allo-HSCT were identified in the EBMT database. The year of allo-HSCT ranged from 2004 to 2019, median 2014. Allo-HSCT was performed at a median (range) of 34 (6-172) months after the diagnosis of myeloma. The stem cell source was PB in 89%, 37% were matched related donor and 39% matched unrelated donor. Conditioning was reduced intensity in 72% and myeloablative in 28%. Disease status at allo-HSCT was CR in 9%, VGPR in 35 %, PR in 43%, SD/MR in 7% and progression in 6%. The median age (range) at the first Dara infusion was 55 (32-71) yrs with a male to female distribution of 70/51. Dara was administered either alone (n=70) or in combination with other anti-myeloma directed therapy (n=51). The first dose of Dara was given at a median (range) of 30 (1-173) months post-allo-HSCT. Fifteen patients started Dara in the first 6 months after allo-HSCT, 50% of patients in the first 2.5 years, 22% in 2.5 to 5 years, and 28% more than five years after allo-HSCT. Among patients with available data, 45% ha