Checkpoint Blockade for Treatment of Relapsed Lymphoma Following Allogeneic Hematopoietic Cell Transplant: Use May be Complicated By Onset of Severe Acute Graft Versus Host Disease

• Published in: Blood 2016-12, Vol.128 (22), p.1163-1163
• Main Authors: Haverkos, Bradley M., Schowinksy, Jeffrey, Kaplan, Jeffrey, Kamdar, Manali, Kanate, Abraham Sebastian, Saad, Ayman, Mehta, Amitkumar, Ganguly, Siddhartha, Flowers, Mary E.D., Fenske, Timothy S., Hari, Parameswaran, Hamadani, Mehdi, Lowsky, Robert, Andritsos, Leslie, Jagasia, Madan H., Brown, Stacey, Armand, Philippe, Merryman, Reid W., Bachanova, Veronika, Stephens, Deborah M, Nakamura, Ryotaro, Gutman, Jonathan A, Devine, Steven M.
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V128.22.1163.1163

▪ Introduction: Allogeneic Hematopoietic-cell transplantation (allo-HCT) may elicit immunological graft versus-tumor effects against tumor cells. However, these immune responses can be misdirected towards normal host organs, resulting in graft-versus host disease (GVHD). Acute GVHD (aGVHD) develops after activation and maturation of antigen-presenting cells, which then leads to donor T-cell activation, expansion, and destruction of host tissue by effector cells. The programmed death (PD) pathway serves as a checkpoint to limit T-cell-mediated immune responses. Blocking the PD1 receptor results in T-cell activation, proliferation, and can induce a potent immunotherapeutic antitumor effect. In the post-allogeneic HCT setting there is concern that activating T-cells via PD1 blockade may induce GVHD (Blazar, J Immunol 2003). While there have been several cases of severe and even fatal transplant-related complications, including GVHD, when nivolumab was given for disease control prior to allo-HCT, less is known about its use in managing relapse after HCT. A few case reports suggest it may be safe (Herbeaux, ASH 2015; Angenendt, BMT 2015; Yared, BMT 2016). Methods:With IRB approval, we conducted a multicenter, retrospective analysis of lymphoma patients (pts) who received monoclonal antibodies against PD1 after allo-HCT. We contacted 10 U.S. transplant programs with the highest volumes of lymphoma pts undergoing HCT, as provided by the Center for International Bone Marrow Transplant Registry (CIBMTR), to derive an estimate of the safety and toxicity of PD1 blockade post allograft. Additional sites were surveyed based on recommendation from these initial 10 sites. Descriptive statistics were used to summarize patient characteristics and clinical outcomes. Response assessments were defined according to revised Lugano criteria (Cheson, 2014). GVHD stage/grade was recorded according to Consensus scoring severity index. PD1 and PDL1 immunohistochemical (IHC) stains were performed on 2 pts' liver biopsies treated at University of Colorado (CU). Results:We surveyed 23 sites with 21 replies to date. 8 sites reported no experience using anti-PD1 after allo-HCT. 13 sites identified 27 lymphoma pts (26 classical Hodgkin lymphoma) who received a monoclonal antibody against PD1 for relapsed disease after allo-HCT (24 nivolumab, 3 pembrolizumab). Table 1 highlights patient characteristics prior to treatment with anti-PD1. At a median follow up of 217 days (range 26-560) after