1.
Non-Myeloablative Allogeneic Transplantation with Post-Transplant Cyclophosphamide after Immune Checkpoint Inhibition for Classic Hodgkin Lymphoma: a Retrospective Cohort Study
Paul, S., Zahurak, M., Luznik, L., Ambinder, R. F., Fuchs, E. J., Bolanos-Meade, J., Wagner-Johnston, N., Swinnen, L. J., Schoch, L., Varadhan, R., et al
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2020
Abstract
BACKGROUND Immune checkpoint inhibitors (ICIs) are approved in relapsed classic Hodgkin lymphoma (cHL). The safety and effectiveness of allogeneic blood or marrow transplantation (alloBMT) in ICI pre-treated cHL patients remain unclear. The aim of this study is to assess outcomes of cHL patients receiving ICIs before alloBMT using post-transplantation cyclophosphamide (PTCy) graft-versus-host-disease (GVHD) prophylaxis. METHODS We performed a retrospective study of relapsed/refractory cHL patients undergoing alloBMT with PTCy at Johns Hopkins between Nov 2004 and Sept 2019. Engraftment, GVHD incidence, non-relapse mortality (NRM), progression free survival (PFS) and overall survival (OS) were compared between patients receiving pre-alloBMT ICI or standard salvage chemotherapy. FINDINGS We identified 105 consecutive relapsed/refractory cHL patients, of which 37 (35.2%) received ICIs and 68 (64.7%) received chemotherapy without ICIs (no-ICI) before alloBMT. ICI and no-ICI patients experienced a 3-year estimated OS of 94% versus 78%, [hazard ratio (HR) 0.35 (95% CI: 0.08-1.56), P=0.17) and a 3-year estimated PFS of 90% and 65% [HR 0.3 (95 % CI: 0.09-1), P=0.05], respectively. We observed no statically significant difference in the 12-month cumulative incidence of acute grade II-IV GVHD or in the 24-month incidence of chronic GVHD. INTERPRETATION ICIs do not increase acute or chronic GVHD incidence compared to salvage chemotherapy. cHL patients receiving ICIs prior to alloBMT experienced outstanding PFS and OS. Thus ICI therapy is safe in cHL patients when undergoing alloBMT with PTCy and may improve post-alloBMT disease progression and survival. FUNDING National Institutes of Health, National Cancer Institute grants.
2.
Haploidentical Bone Marrow Transplantation with Post-Transplant Cyclophosphamide Using Non-First-Degree Related Donors
Elmariah, H., Kasamon, Y. L., Zahurak, M., Macfarlane, K. W., Tucker, N., Rosner, G. L., Bolanos-Meade, J., Fuchs, E. J., Wagner-Johnston, N., Swinnen, L. J., et al
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2018
Abstract
Outcomes of nonmyeloablative (NMA) haploidentical (haplo) blood or marrow transplant (BMT) with post-transplantation cyclophosphamide (PTCy) using non-first-degree relatives are unknown. We evaluated 33 consecutive adult patients (median age 56 years) with hematologic malignancies who underwent NMA haplo T-cell replete BMT with PTCy at Johns Hopkins using second- or third-degree related donors. Donors consisted of 10 nieces (30%), 9 nephews (27%), 7 first cousins (21%), 5 grandchildren (15%), and 2 uncles (6%). Thirty-one patients (94%) reached full donor chimerism by day 60. The estimated cumulative incidence (CuI) of grade II-IV acute GVHD (aGVHD) at day 180 was 24% (90% CI: 9-38%). Only 1 patient experienced grade III-IV aGVHD. At 1 year, the CuI of chronic GVHD was 10% (90% CI: 0-21%). The CuI of nonrelapse mortality at 1 year was 5% (90% CI: 0-14%). At 1 year, the probability of relapse was 31% (90% CI: 12-49%), progression-free survival was 64% (90% CI: 48-86%) and overall survival was 95% (90% CI: 87-100%). The 1-year probability of GVHD-free, relapse free survival was 57% (90% CI: 41-79%). NMA haplo BMT with PTCy from non-first-degree relatives is an acceptably safe and effective alternative donor platform, with results similar to those seen with first degree relatives.