Reduced cumulative PTCy exposure for GvHD prophylaxis after allo-HSCT

Results from a retrospective single-center cohort study evaluating clinical outcomes in adults receiving reduced (<100 mg/kg; n = 71) vs standard (≥100 mg/kg; n = 109) cumulative post-transplant cyclophosphamide (PTCy) exposure for graft-versus-host disease (GvHD) prophylaxis after allogeneic hematopoietic stem cell transplantation (allo-HSCT) were published in Transplantation and Cellular Therapy by Soto et al. Primary endpoints included acute GvHD (aGvHD), chronic GvHD (cGvHD), relapse, non-relapse mortality (NRM), and overall survival (OS). 

Key data: Reduced cumulative PTCy exposure <100 mg/kg vs standard exposure ≥100 mg/kg was associated with higher rates of aGvHD (57.7% vs 37.0%; odds ratio [OR], 2.31; 95% confidence interval [CI], 1.21–4.49; p = 0.009), Grade 2–4 aGvHD (25.4% vs 12.8%; OR, 2.30; 95% CI, 1.07–5.08; p = 0.035), and moderate-to-severe cGvHD (21.1% vs 7.3%; OR, 3.48; 95% CI, 1.29–10.12; p = 0.010). Reduced cumulative PTCy exposure was also associated with greater use of second-line GvHD-directed therapy with ruxolitinib and/or extracorporeal photopheresis (ECP) vs standard exposure (34.4% vs 19.8%; OR, 2.12; 95% CI, 1.05–4.31; p = 0.036). In multivariable analyses, reduced cumulative PTCy exposure remained independently associated with aGvHD (OR, 2.29; 95% CI, 1.18–4.53; p = 0.016) and moderate-to-severe cGvHD (OR, 4.07; 95% CI, 1.52–11.63; p = 0.005). No significant differences in relapse incidence, NRM, or OS were observed between exposure groups.

Key learning: Reduced cumulative PTCy exposure was associated with increased rates of aGvHD, a greater burden of clinically significant cGvHD, and greater use of second-line GvHD-directed therapy. These findings suggest that adequate cumulative PTCy exposure may be important for effective GvHD prophylaxis and support prospective studies to define the optimal cumulative dose.