Patterns, risk factors and management of CD19-directed chimeric antigen receptor T-cell therapy failure in CNS lymphoma
Kaulen LD, Karschnia P, Doubrovinskaia S, Abramson JS, Soumerai JD, Martinez-Lage M, Haydu JE, Shankar GM, Patel C, Choi BD, Barnes JA, El-Jawahri A, Hochberg EP, Johnson PC, Wick W, Maus MV, Chen YB, Frigault MJ, Dietrich J (2026)
Publication Type: Journal article
Publication year: 2026
Journal
Book Volume: 19
Article Number: 2
Journal Issue: 1
DOI: 10.1186/s13045-025-01761-8
Abstract
Background: CD19-directed chimeric antigen receptor T-cell therapy (CD19-CAR) has yielded encouraging efficacy in CNS lymphomas (CNSL), but most patients ultimately experience progressive disease (PD). Risk factors, progression patterns as well as optimal salvage therapies remain unclear. Methods: Clinical and radiological characteristics of CD19-CAR failure were therefore retrospectively defined in CNSL treated at Massachusetts General Hospital from 2018 to 2024. PD patterns were defined as local or distant. CNS-progression-free survival from CD19-CAR infusion (CNS-PFS1) and first subsequent progression (CNS-PFS2) were analyzed. Results: CD19-CAR achieved a 60% overall response rate (45% complete (CR), 15% partial response) in 60 recurrent CNSL. Median CNS-PFS1 was 4 months with radiographic PD in 36 patients (local 23.3%; local and distant 16.7%; distant 20%). PD patterns were associated with prior CD19-CAR response: Distant relapse typically occurred after CR whereas local PD followed CD19-CAR refractory disease. Peripherally contrast enhancing CNSL (pCE) at CD19-CAR infusion correlated with refractory disease. Leptomeningeal involvement (LMD) was associated with recurrence after CR. On multivariable Cox regression, pCE (Hazard ratio [HR]: 2.75; 95%-Confidence interval [CI]: 1.08–6.68, p = 0.03) and LMD (HR: 2.72; CI: 1.20–6.25, p = 0.02) were independently associated with shorter CNS-PFS1. At progression, peripheral CD19+-B-cell aplasia suggested CD19-CAR persistence in 93% of patients. Median CNS-PFS2 after CD19-CAR failure was one month. Salvage immune checkpoint inhibition, and lenalidomide with rituximab/tafasitamab yielded prolonged responses. Conclusions: This study identifies novel radiological risk factors for CD19-CAR failure in CNSL, namely pCE and LMD. Outcome in this setting is unfavorable and encouraging salvage treatments warrant prospective evaluation.
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Germany (DE)How to cite
APA:
Kaulen, L.D., Karschnia, P., Doubrovinskaia, S., Abramson, J.S., Soumerai, J.D., Martinez-Lage, M.,... Dietrich, J. (2026). Patterns, risk factors and management of CD19-directed chimeric antigen receptor T-cell therapy failure in CNS lymphoma. Journal of Hematology & Oncology, 19(1). https://doi.org/10.1186/s13045-025-01761-8
MLA:
Kaulen, Leon D., et al. "Patterns, risk factors and management of CD19-directed chimeric antigen receptor T-cell therapy failure in CNS lymphoma." Journal of Hematology & Oncology 19.1 (2026).
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