Impact of Rituximab and Host/Donor Fc Receptor Polymorphisms after Allogeneic Hematopoietic Cell Transplantation for CD20+ B Cell Malignancies.

ABSTRACT

We previously reported a 24% 1-year relapse rate in 93 older or medically unfit patients with CD20+ B cell malignancies after allogeneic hematopoietic cell transplantation (HCT) with low-intensity conditioning. The current prospective study tested the hypothesis that disease relapse could be reduced and overall survival (OS) improved by peritransplantation administration of rituximab (RTX). Sixty-three patients received RTX (375 mg/m2/day) on days -3, +10, +24, and +38 along with 2 to 3 Gy total body irradiation with or without fludarabine (30 mg/m2 for 3 days). Median RTX levels of >25 µg/mL were achieved through day +84 after transplantation, but RTX level was not correlated with relapse or graft-versus-host disease (GVHD). HCT recipients with F/F and V/F FCγRIIIa polymorphisms showed a trend toward a higher relapse rate compared with those with V/V polymorphism (P= .15). No difference in outcome was found based on V/V donor pairing. Five-year relapse rates were similar between RTX-treated patients and historical controls (32% versus 28%; P = .94). RTX-treated patients had greater 5-year OS (47% versus 38%; P = .13) and progression-free survival (41% versus 32%; P = .12) compared with historical controls who underwent HCT without RTX, although the difference was not statistically significant. The incidence of acute GVHD was similar in the 2 groups (grade II-IV, 57% versus 56%; grade III-IV, 13% versus 17%), but the 5-year incidence of chronic GVHD was higher among RTX-treated patients (62% versus 47%). In patients with relapsed or refractory non-Hodgkin lymphoma, peritransplantation RTX neither reduced relapse nor improved GVHD. The role of donor-recipient pairing by FCγRIIIa polymorphisms in outcomes remains to be determined.