Characteristics of Patients with Relapsed/Refractory Burkitt Non-Hodgkin Lymphoma (NHL): Impact on the Feasibility of CAR-T Cell Therapy

Background Burkitt NHL (BL) is a rare hematologic malignancy that occurs in younger adults and is highly curable with aggressive chemoimmunotherapy induction regimens. Unfortunately, patients that are refractory or relapse after these regimens fare poorly and treatment guidelines are not well established. The typical approach is with standard platinum-based salvage regimens; those who obtain a complete remission (CR) become eligible for autologous or allogeneic stem cell transplantation (SCT). Chimeric antigen receptor T (CAR-T) cell therapy and bispecific antibodies offer potential novel approaches for these patients, especially those who are unable to achieve remission in order to proceed with SCT; however, CAR-T therapy is not approved nor even tested in BL other than promising single case reports (Avigdor A, Bone Marrow Transplant. 2018 May 24). The goal of this study was to learn the clinical features and outcome of R/R BL in order to design a prospective strategy for novel therapy use in relapsed/refractory (R/R) BL patients. Methods We reviewed the Mayo Clinic Lymphoma database to find cases of BL diagnosed and treated between 1/1/2000 - 9/30/2018. Forty-two cases were identified and 32 (76%) entered CR and never relapsed; 10 (24%) did not respond or relapsed and are the focus of this report. Demographic, clinical response to treatment regimens, and long-term outcomes were extracted from the Mayo Clinic electronic medical record. Results The 10 patients with R/R BL had a median age of 41 years (range, 28-59); all had received aggressive chemoimmunotherapy induction regimens; 7 were primary refractory and 3 relapsed within 3 months (2-4) of achieving first CR. All 3 patients that relapsed did so in the central nervous system (CNS) despite receiving CNS prophylaxis with their induction therapy regimen. The response to salvage therapy was 30% (3/10) with 10% CR and 30% (3/10) proceeded to autologous SCT (no patients made it to allogenic SCT). The median progression free survival (PFS) and overall survival (OS) from diagnosis of all 10 patients was 4 months (1-9) and 70% (7/10) died within 6±4 months from date of relapse. The 3 patients with relapsed BL survived 7, 10, and17 months from date of relapse. The 3 patients who did survive to receive a SCT lived 2, 4, and 13 months from date of SCT. None of the 10 patients survived past 26 months from date of diagnosis. Conclusions Patients with R/R BL represent an uncommon and unique subset of aggressive NHL that require a new therapeutic approach such as CAR-T. Our study demonstrates the very poor outcome with traditional salvage therapies and the very short OS of these young, otherwise healthy patients. We recommend that these patients be considered as emergencies and referred promptly for novel therapies such as CAR-T trials at the very first sign of treatment failure. Waiting with the intent of attaining response to traditional therapies is futile. Insurance approval initiation and harvesting of T-cells should be rapidly performed, preferably prior to initiating salvage therapy, given the rapid clinical deterioration and demise of these patients. Kenderian: Lentigen: Research Funding; Novartis: Patents & Royalties, Research Funding; Tolero: Research Funding; Humanigen: Other: Scientific advisory board , Patents & Royalties, Research Funding; Morphosys: Research Funding; Kite/Gilead: Research Funding. Bennani:Kite Pharma: Other: Advisory board; Bristol-Myers Squibb: Research Funding; Adicet Bio: Other: Advisory board; Adicet Bio: Other: Advisory board; Seattle Genetics: Other: Advisory board; Purdue Pharma: Other: Advisory board; Seattle Genetics: Other: Advisory board; Purdue Pharma: Other: Advisory board; Purdue Pharma: Other: Advisory board; Bristol-Myers Squibb: Research Funding; Adicet Bio: Other: Advisory board; Kite Pharma: Other: Advisory board; Kite Pharma: Other: Advisory board; Seattle Genetics: Other: Advisory board; Bristol-Myers Squibb: Research Funding. Nowakowski:Selvita: Membership on an entity's Board of Directors or advisory committees; NanoString: Research Funding; MorphoSys: Consultancy, Research Funding; Genentech, Inc.: Research Funding; F. Hoffmann-La Roche Ltd: Research Funding; Curis: Research Funding; Bayer: Consultancy, Research Funding; Celgene: Consultancy, Research Funding.