BCMA CAR-T induces complete and durable remission in refractory plasmablastic lymphoma.

• Type of Material: Article
• Authors: Sharmila Raghunandan, Emory University; Melinda Pauly, Emory University; William G. Blum, Emory University; Muna Qayed, Emory University; Madhav V. Dhodapkar, Emory University; Mohamed Elkhalifa, Emory University; Benjamin Watkins, Emory University; Michelle Schoettler, Emory University; Edwin Horwitz, Emory University; Suhag Parikh, Emory University; Shanmuganathan Chandrakasan, Emory University; Kathryn Leung, Emory University; Elyse Bryson, Emory University; Laura Deeb, Emory University; Jonathan L. Kaufman, Emory University; Diana Worthington-White, Emory University; Adina Alazraki, Emory University; Jordan M. Schecter, Janssen Research and Development; Deepu Madduri, Janssen Research and Development; Carolyn C. Jackson, Janssen Research and Development; Enrique Zudaire, Janssen Research and Development; Agne Taraseviciute-Morris, Janssen Research and Development; Alexander Babich, Janssen Research and Development; Tonia Nesheiwat, Legend Biotech USA Inc; Martin Vogel, Janssen Global Services LLC; Nikoletta Lendvai, Janssen Research and Development; Lida Pacaud, Legend Biotech USA Inc; Kirsten M. Williams, Emory University
• Language: English
• Date: 2023-05
• Publisher: BMJ
• Publication Version: Final Published Version
• Copyright Statement: © Author(s) (or their employer(s)) 2023.
• License: Creative Commons Attribution-NonCommercial 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1136/jitc-2023-006684
• Title of Journal or Parent Work: J Immunother Cancer
• Volume: 11
• Issue: 5
• Grant/Funding Information: The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
• Keywords: Immunotherapy; Hematopoietic Stem Cell Transplantation; Receptors, Chimeric Antigen; Plasmablastic Lymphoma; Pediatrics; Adolescent; Humans; Multiple Myeloma; B-Cell Maturation Antigen
• Research Categories: Health Sciences, Human Development; Health Sciences, Oncology

Abstract

Plasmablastic lymphoma (PBL) is a rare subtype of aggressive large B-cell lymphoma, with a dismal prognosis despite aggressive therapies. New approaches are needed for those with refractory disease. PBL expresses antigens similar to multiple myeloma (MM), including B-cell maturation antigen (BCMA). Chimeric antigen receptor T-cell (CAR-T) therapy directed against BCMA has shown efficacy for the treatment of heavily pretreated MM with low rates of grades 3 and 4 cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) in a phase Ib/II trial (A Study of JNJ-68284528, a CAR-T Directed Against BCMA in Participants With Relapsed or Refractory Multiple Myeloma (CARTITUDE-1), NCT03548207). However, data for the use of BCMA CAR-T for treating PBL are lacking.We report a challenging case of multiple refractory PBL that emerged from B-cell acute lymphoblastic leukemia in an adolescent who failed to respond to an allogeneic hematopoietic cell transplant. The patient developed rapidly advancing disease despite withdrawal of immunosuppression, treatment with etoposide, ibrutinib, and daratumumab, prompting consideration of BCMA CAR-T (under emergency investigational new drug (eIND)). The patient achieved a complete remission (CR), without recurrent acute graft versus host disease (GVHD), CRS or ICANS after BCMA CAR-T therapy. BCMA CAR-T expansion was detected in vivo, peaking on day 15. The patient remains in CR for more than a year post CAR-T therapy, supporting consideration of immunotherapy for future patients with refractory PBL, a disease with few treatment options.