Monoclonal Antibodies in Conditioning Regimens for Hematopoietic Cell Transplantation

Abstract

Monoclonal antibodies are increasingly being incorporated in conditioning regimens for autologous or allogeneic hematopoietic cell transplantation (HCT). The benefit of adding rituximab to autologous HCT regimens is purportedly related to in vivo purging of clonal B cells. Randomized trials comparing the addition (or not) of rituximab to high-dose therapy regimens are lacking. No benefit of standard-dose radioimmunotherapy-based regimens for autografting in aggressive lymphomas was seen in a randomized controlled study. The incorporation of rituximab into allogeneic HCT regimens aims to improve responses while reducing nonrelapse mortality resulting from acute graft-versus-host disease. The optimal dose and administration schedule of rituximab in this setting are unknown, and potentially serious complications from increased infections owing to prolonged (and profound) cytopenias or persistent hypogammaglobulinemia are of concern. Radioimmunotherapy-based conditioning for allografting holds promise as a modality to optimize tumor control and synergize adoptive immunotherapy effects, but it remains experimental at this time. The addition of alemtuzumab to allogeneic HCT regimens is associated with prolonged lymphopenia and impaired immune reconstitution, high relapse rates, and serious infections. The optimal dose and schedule of alemtuzumab to avoid prolonged immune paresis remain elusive. It is anticipated that additional monoclonal antibodies will soon become available that can be incorporated into HCT regimens after safety and clinical efficacy are demonstrated.

Proceedings from the National Cancer Institute’s Second International Workshop on the Biology, Prevention, and Treatment of Relapse after Hematopoietic Stem Cell Transplantation: Part III. Prevention and Treatment of Relapse after Allogeneic Transplantation

“…may deepen remissions through effects on cancer cells or the tumor microenvironment and thus improve outcomes. A role for novel agents in the pre-transplant setting is suggested by observations of improved AlloSCT outcomes following their use in “bridge” therapy, such as with tyrosine kinase inhibitors in Philadelphia chromosome-positive acute lymphoblastic leukemia (ALL) (9) and brentuximab vedotin in Hodgkin’s lymphoma (10); distinct toxicity profiles and unique mechanisms of action have led to investigation of incorporating monoclonal antibodies into reduced-intensity conditioning (RIC) regimens, resulting in immunomodulatory as well as direct antitumor effects (11). New cancer drugs with novel targets and innovative methods of drug delivery are entering the clinic at a phenomenal rate; their potential to permit or augment GVT is an important research opportunity.…”

Outcomes of rituximab‐BEAM versus BEAM conditioning regimen in patients with diffuse large B cell lymphoma undergoing autologous transplantation

“…This study was performed when the use of rituximab was not highly prevalent and the first exposure to an anti‐CD20 monoclonal antibody likely resulted in the observed response rates in a predominantly rituximab‐naïve patient population. Similarly, a few earlier studies that primarily enrolled immunotherapy‐naïve patients revealed improved outcomes with incorporation of monoclonal antibody with mobilization approaches or during the posttransplantation period, but these findings may not be relevant in the current era of rituximab …”