Real-World Outcomes of CD19CAR T Cell Therapy in Adult Patients with Relapsed Refractory Transformed Indolent Lymphoma

• Published in: Blood 2024-11, Vol.144, p.524-524
• Main Authors: Kambhampati, Swetha, Merryman, Reid W., Wang, Yan, Gaulin, Charles, Bezerra, Evandro, Voorhees, Timothy, Seshadri, Madhav R, Falade, Ayo S, Habib, Alma, Ayers, Amy A., Bailey, Megumi, Brown, Annette, Bailey, Neil, Patel, Krish, Andreadis, Charalambos, Kittai, Adam S, Jacobson, Caron A., Palmer, Joycelynne Michelle, Forman, Stephen J., Nastoupil, Loretta, Budde, Lihua E.
• Format: Article
• Language: English
• ISSN: 0006-4971
• DOI: 10.1182/blood-2024-198749

Introduction Transformation of indolent lymphomas to diffuse large B-cell lymphoma (DLBCL) is associated with poor outcomes, particularly for patients (pts) with relapsed or refractory (r/r) disease. While chimeric antigen receptor (CAR) T cell therapy has revolutionized the management of r/r DLBCL and is approved for transformed indolent lymphoma (tiNHL), pts with tiNHL were largely underrepresented in the pivotal trials leading to the approval of CD19CAR. In this study, we evaluated the safety and efficacy of standard of care CD19CAR T in adults with r/r tiNHL relative to de novo DLBCL (dDLBCL). Methods We conducted a multicenter retrospective study in adults treated at 6 centers. Eligibility criteria included age ≥ 18 years old, diagnosis of DLBCL/high-grade B-cell lymphoma (HGBCL) (both de novo and transformed), r/r disease, and receipt of SOC CD19CAR T. Pts who received CAR T on clinical trials were excluded. We defined tiNHL as DLBCL/HGBCL transformed from follicular lymphoma, marginal zone lymphoma, or Waldenstrom's macroglobulinemia. Pts with Richter's syndrome were excluded. Safety endpoints included incidence and severity of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) per American Society for Transplantation and Cellular Therapy (ASTCT) consensus grading. Response was assessed using 2014 Lugano Criteria. Efficacy endpoints include best overall response rate (ORR) (proportion of pts achieving a complete or partial response), complete response rate (CRR), progression/relapse-free survival (PFS) and overall survival (OS). Pts were followed post-CAR T through 6/2023, lost to follow-up, or death. The study was approved by the Institutional Review Board at each site. Results A total of 1182 pts were included (338 (29%) tiNHL, 884 (71%) dDLBCL) with the CAR T infusion date ranging from 12/2017 to 10/2022. In the tiNHL cohort, 284 (84%) pts transformed from FL, 41 (12%) MZL, 13 (4%) WM. Most baseline characteristics were comparable in the tiNHL and dDLBCL cohorts. Among all pts, the median age at CAR T cell therapy was 64 (range: 18-89) years and 36% were women. At the time of CAR T cell therapy, 934 (79%) pts had advanced stage disease (III-IV), 649 (55%) had an elevated LDH, 479 (41%) had more than one site of extranodal disease, and 135 (11%) had bulky disease (defined as ≥ 10 cm). Most pts (77%) received axicabtagene ciloleucel. Compared to dDLBCL, tiNHLpts were more heavily pre-treated (67% vs 5