Cancer Res Treat.  2023 Oct;55(4):1363-1368. 10.4143/crt.2023.371.

Long-term Complete Remission of Decitabine-Primed Tandem CD19/CD22 CAR-T Therapy with PD-1 and BTK Inhibitors Maintenance in a Refractory Primary Central Nervous System Lymphoma Patient

• Zou R
• Zhou X
• Liu H
• Wang P
• Xia F
• Kang L
• Yu L
• Wu D
• Jin Z
• Qu C

• KMID: 2547810
• DOI: http://doi.org/10.4143/crt.2023.371

Abstract

Primary central nervous system lymphoma (PCNSL) is a rare and aggressive non-Hodgkin’s lymphoma that affects the brain, eyes, cerebrospinal fluid, or spinal cord without systemic involvement. The outcome of patients with PCNSL is worse compared to patients with systemic diffuse large B-cell lymphoma. Given potential mortality associated with severe immune effector cell-associated neurotoxicity syndrome (ICANS), patients with PCNSL have been excluded from most clinical trials involving chimeric antigen receptor T-cell (CAR-T) therapy initially. Here, we report for the first time to apply decitabine-primed tandem CD19/CD22 dual-targeted CAR-T therapy with programmed cell death-1 (PD-1) and Bruton’s tyrosine kinase (BTK) inhibitors maintenance in one patient with multiline-resistant refractory PCNSL and the patient has maintained complete remission (CR) for a 35-month follow-up period. This case represents the first successful treatment of multiline resistant refractory PCNSL with long-term CR and without inducing ICANS under tandem CD19/CD22 bispecific CAR-T therapy followed by maintenance therapy with PD-1 and BTK inhibitors. This study shows tremendous potential in the treatment of PCNSL and offers a look toward ongoing clinical studies.

Keyword

Chimeric antigen receptor T-cell therapy; Primary central nervous system lymphoma; Diffuse large B-cell lymphoma; CD19/CD22; Decitabine

Figure

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  Fig. 1 Clinical efficacy after chimeric antigen receptor T-cell (CAR-T) therapy in a multiline-resistant refractory primary central nervous system lymphoma patient. Representative magnetic resonance imaging of untreated, before CAR-T infusion, 1 month after CAR-T infusion and 27 months after CAR-T infusion were shown. (A, E) Occupancies in the brainstem, right frontoparietal temporal lobe, and basal ganglia area were observed at diagnosis. (B, F) The previous lesions decreased dramatically, but a new left-sided lesion appeared before CAR-T therapy. (C, G) no brain lesions were shown 1 month after CAR-T therapy. (D, H) The patient remained in complete remission until now. The red arrow pointed to the location of the tumor.

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  Fig. 2 Immunohistochemical staining for markers shows strong positive for CD19 (A) and CD22 (B), weak positive for programmed cell death-1 (PD-1) (C).

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  Fig. 3 Hematological toxicities, cytokines, and CAR-T copies in a multiline-resistant refractory PCNSL patient. (A) Changes of WBC, NEU, and PLT levels after CAR-T therapy. (B–D) Changes of IL-6, CRP, and Fer levels after CAR-T therapy. (E) Changes of CAR-T copies at the indicated time points after CAR-T therapy. CAR-T, chimeric antigen receptor T-cell; CRP, C-reactive protein; IL-6, interferon 6; NEU, neutrophil; PCNSL, primary central nervous system lymphoma; PLT, platelet; WBC, white blood cell.

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  Fig. 4 The treatment timeline in a multiline resistant refractory PCNSL patient. CAR-T, chimeric antigen receptor T-cell; MRI, magnetic resonance imaging; MTX, methotrexate; PBMCs, peripheral blood mononuclear cells; PCNSL, primary central nervous system lymphoma; PD, progression of disease; q3w, every 3 weeks; q12h, every 12 hours; WBRT, whole-brain radiation therapy.

Reference

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