Immunotherapy and Chemotherapy Can Result in Long-Term Survival for Patients with Recurrent or Progressive Non-Hodgkin’s Lymphoma after Reduced-Intensity Allogeneic Stem Cell Transplantation.
Authors: Bishop Michael R. , Dean Robert M. , Wilson Wyndham H. , Odom Jeanne , Steinberg Seth , Krumlauf Michael , Kasten-Sportes Claude , Pavletic Steven Z. , Castro Kathleen , Chinn Tracey , Gress Ronald , Fowler Daniel H. 
Published: October 2019

Abstract
Reduced-intensity allogeneic stem cell transplantation (RIST) has been demonstrated to clinically benefit patients (pts) with relapsed, chemotherapy-sensitive non-Hodgkin’s lymphoma (NHL). The most significant challenge after RIST is treatment of recurrent or progressive disease, and the subsequent outcomes of NHL pts, who either have progressed or relapsed after RIST, have not been previously reported. To address this question we performed a retrospective analysis on 35 pts who had undergone RIST from HLA-matched siblings for refractory/relapsed NHL (excluding CLL/SLL). Outcomes were analyzed from Day +100 on, as all pts had achieved complete donor chimerism by this time point and this was a scheduled time of disease assessment as per protocol. All pts had received the identical reduced-intensity conditioning regimen consisting of fludarabine and cyclophosphamide and had received cyclosporine (CSA)-based GVHD prophylaxis. For pts with recurrent or progressive NHL, we employed a sequential approach of CSA withdrawal, followed by rituximab (ritux), followed by donor lymphocyte infusion (DLI), and then followed by chemotherapy +/− DLI; specific treatment was dependent upon the presence or absence of GVHD and CD20 expression. At Day +100 post-RIST 23/35 pts were in a complete remission (CR) of which 4 (DLC = 2, FCC = 1, MCL = 1) were subsequently observed to relapse. The disease status at Day +100 among the remaining 12 pts (DLC = 10, FCC = 1, PTCL =1) not in CR at Day +100 post-RIST was partial remission (PR) = 2, stable disease (SD) = 1, and progressive disease (PD) = 9, as compared to pre-RIST evaluation. Among the 4 pts who relapsed after an initial CR post-RIST, 3 had CSA withdrawn, 1 received ritux, 3 received DLI, and 2 received chemotherapy + ritux. There subsequently were 3 CR and 1 PR. CR were maintained 12, 24+, and 26+ months after intervention. Three of these 4 pts are alive, and the 12 month probability of survival beyond Day +100 post-RIST was 75%. Among the 12 pts who were not in CR at Day +100 post-RIST, all 12 subsequently had CSA withdrawn, 7 received ritux, 5 received chemotherapy, and 3 received DLI. For the 2 pts in PR at Day +100 both achieved a CR by 6 months post-RIST. The one SD patient achieved a PR and died +11 months post-RIST. Among the 9 pts with PD at Day +100, 2 achieved CR, which have been maintained for 22+ and 4+ months, respectively. The 12 month probability of survival beyond Day +100 post-RIST for the 12 pts not in CR at Day +100 was 44%. The 12 month probability of survival beyond Day +100 post-RIST for all 16 pts was 52%. These data demonstrate that relapse after achievement of CR post-RIST is low, and that the majority of these patients can achieve sustained survival with post-transplant therapies. For NHL pts who do not initially achieve a CR at Day +100 post-RIST, subsequent outcome appears to correlate with disease status at Day +100; however, sustained, complete remissions could be achieved for a minority of patients with progressive disease post-RIST. These data indicate that further immunotherapy and additional chemotherapy can result in significant long-term survival for NHL pts with recurrent or progressive disease post-RIST.