Itacitinib

The NMA PBSC haplo transplant is associated with a higher risk of morbidity and mortality from the cytokine (IL-6 and others)-driven CRS and perhaps higher incidence of acute and chronic GVHD compared to bone marrow (BM) haplo allografting with post-transplant cyclophosphamide (PTCy). Notably, severe CRS (grade 3 and higher) appears to be more common in older patients (≥ 60 years) and is associated with significantly higher non-relapse mortality (NRM) in this patient group. Itacitinib has demonstrated safety, tolerability, ability to inhibit cytokines, including IL-6. Data also suggest that itacitinib can be administered safely in peri- and post-transplant period in the setting of Posttransplant CY immune prophylaxis and haploPBSCT with no evidence of delayed engraftment or delayed count recovery, with significant reduction in CRS compared to historical control, and a low rate of aGVHD, cGVHD, and NRM, and with no increase in relapse risk. Thus, the investigators propose a clinical study in which itacitinib will be used prophylactically in recipients age 60 years and older to prevent development of severe CRS, reduce severe CRS-associated NRM, and the incidence of severe GVHD, thus allowing further reduction in posttransplant immunosuppression therapy after PTCy-based NMA related partially-mismatched PB allografting.