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

Autor: Martin Vogel, Muna Qayed, Shanmuganathan Chandrakasan, Sharmila Raghunandan, Melinda Pauly, William G Blum, Madhav V Dhodapkar, Mohamed Elkhalifa, Benjamin Watkins, Michelle Schoettler, Edwin Horwitz, Suhag Parikh, Kathryn Leung, Elyse Bryson, Laura Deeb, Jonathan L Kaufman, Diana Worthington-White, Adina Alazraki, Jordan M Schecter, Deepu Madduri, Carolyn C Jackson, Enrique Zudaire, Agne Taraseviciute-Morris, Alexander Babich, Tonia Nesheiwat, Nikoletta Lendvai, Lida Pacaud, Kirsten M Williams
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Journal for ImmunoTherapy of Cancer, Vol 11, Iss 5 (2023)
Druh dokumentu: article
ISSN: 2051-1426
DOI: 10.1136/jitc-2023-006684
Popis: 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.
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