Case Report: Dual Inhibition of HDAC and BTK for Diffuse Large B-Cell Lymphoma After Failure to CD19-Targeted CAR-T Therapy

Zhu, Weiguo; Shi, Tao; Miao, Wenchun; Liu, Hui; Yuan, Xianggui

doi:10.3389/fimmu.2022.894787

Cited by 5 publications

(5 citation statements)

References 31 publications

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“…Meanwhile, a case reported by Weiguo Zhu et al. considered dual inhibition of HDAC and BTK resulting in long-term remission with R/R DLBCL patients after failure of CAR-T cell therapy with TP53 mutation, which suggests underlying synergistic mechanism between BTK inhibitor and CAR-T cell therapy ( 7 ). Furthermore, BTK inhibitor enabled the reduction of PD-1 and cytotoxic T lymphocyte-associated protein 4 (CTLA-4) to overturn the exhausted T cell phenotype.…”

Section: Discussionmentioning

confidence: 99%

“…Narendranath et al proposed the idea that administration of a BTK inhibitor before T cell collection could promote the level of IL-2 and IFNg, which are associated with high self-renewal ability and production efficacy, respectively, as well as stronger cytotoxicity. Meanwhile, a case reported by Weiguo Zhu et al considered dual inhibition of HDAC and BTK resulting in long-term remission with R/R DLBCL patients after failure of CAR-T cell therapy with TP53 mutation, which suggests underlying synergistic mechanism between BTK inhibitor and CAR-T cell therapy (7). Furthermore, BTK inhibitor enabled the reduction of PD-1 and cytotoxic T lymphocyte-associated protein 4 (CTLA-4) to overturn the exhausted T cell phenotype.…”

Section: Copies/mg; Car-t Cell Expansionmentioning

confidence: 99%

“…In 2017, the first successful case using CD19-directed CAR-T cell therapy was reported for CNS-DLBCL (5). Investigations and studies about CAR-T cell therapy in conjunction with other novel targeted agents, including Bruton's tyrosine kinase (BTK) inhibitor, programmed cell death protein 1 (PD-1) antibody revealed synergistic action for relapsed/refractory (R/R) DLBCL (6)(7)(8). BTK inhibitors could enhance the function and implantation of CAR-T cells (9).…”

Section: Introductionmentioning

confidence: 99%

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Case report: CD19-directed CAR-T cell therapy combined with BTK inhibitor and PD-1 antibody against secondary central nervous system lymphoma

Zhang

Huang²,

Liu³

et al. 2022

Front. Immunol.

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Current therapeutic strategies for central nervous system (CNS) relapse of diffuse large B-cell lymphoma (DLBCL) are extremely limited. Secondary central nervous system lymphoma (SCNSL) also shows a grave prognosis and high mortality. This report describes a young female patient with DLBCL and CNS relapse who received low-dose CD19-directed chimeric antigen receptor T (CAR-T) cell therapy followed with Bruton’s tyrosine kinase inhibitor and programmed cell death protein 1 antibody after several lines of chemotherapy. However, limited reports on CAR-T cell therapy are applied for SCNSL, particularly those in combination with targeted agents. The current treatment combination for this case provides a new regimen for CNS relapse from DLBCL.Clinical Trial RegistrationClinicalTrials.gov number, NCT04666168.

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Section: Discussionmentioning

confidence: 99%

Section: Copies/mg; Car-t Cell Expansionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Case report: CD19-directed CAR-T cell therapy combined with BTK inhibitor and PD-1 antibody against secondary central nervous system lymphoma

Zhang

Huang²,

Liu³

et al. 2022

Front. Immunol.

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“…The achieved ORR was 80%, and the CR was 30% (92). Further case studies have also cited the use of agents like BTKi, histone deacetylase inhibitors, and ibrutinib (93,94).…”

Section: Other Therapiesmentioning

confidence: 98%

Treatment strategies for relapse after CAR T-cell therapy in B cell lymphoma

Negishi,

Girsch,

Siegler

et al. 2024

Front. Pediatr.

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Clinical trials of anti-CD19 chimeric antigen receptor T (CART19) cell therapy have shown high overall response rates in patients with relapsed/refractory B-cell malignancies. CART19 cell therapy has been approved by the US Food and Drug Administration for patients who relapsed less than 12 months after initial therapy or who are refractory to first-line therapy. However, durable remission of CART19 cell therapy is still lacking, and 30%–60% of patients will eventually relapse after CART19 infusion. In general, the prognosis of patients who relapse after CART19 cell therapy is poor, and various strategies to treat this patient population have been investigated extensively. CART19 failures can be broadly categorized by the emergence of either CD19-positive or CD19-negative lymphoma cells. If CD19 expression is preserved on the lymphoma cells, a second infusion of CART19 cells or reactivation of previously infused CART19 cells with immune checkpoint inhibitors can be considered. When patients develop CD19-negative relapse, targeting different antigens (e.g., CD20 or CD22) with CAR T cells, investigational chemotherapies, or hematopoietic stem cell transplantation are potential treatment options. However, salvage therapies for relapsed large B-cell lymphoma after CART19 cell therapy have not been fully explored and are conducted based on clinicians' case-by-case decisions. In this review, we will focus on salvage therapies reported to date and discuss the management of relapsed/refractory large B-cell lymphomas after CART19 cell therapy.

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“…Perhaps these agents, including zanubrutinib, could be administered concurrently as immune modifiers after CAR-T infusion, as well as synergizing with the anti-lymphoma effect. There is a single case report on zanubrutinib combined with an oral histone deacetylase inhibitor (HDACi), chidamide, in a 70-year old patient with DLBCL who relapsed 12 months after CAR-T therapy ( 85 ). He failed salvage chemotherapy with gemcitabine, dexamethasone and cisplatin, and suffered from progressive and symptomatic lung infiltration.…”

Section: Zanubrutinib In Other Lymphoid Malignanciesmentioning

confidence: 99%

Zanubrutinib for the treatment of lymphoid malignancies: Current status and future directions

Wolska-Washer

Robak

2023

Front. Oncol.

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Zanubrutinib (BGB-3111, Brukinsa®, BeiGene) is a next-generation irreversible inhibitor of Bruton’s tyrosine kinase (BTK), developed by BeiGene in 2012 for the treatment of B-cell malignancies. It was designed to minimize off-target inhibition of TEC- and EGFR-family kinases. Zanubrutinib is more selective than ibrutinib for BTK versus EGFR, FGR, FRK, HER2, HER4, ITK, JAK3, LCK, BLK and TEC. In addition, compared to ibrutinib, zanubrutinib has improved oral absorption and better target occupancy. Zanubrutinib demonstrated a lower incidence of off-target toxicities and reduced severity than ibrutinib. Moreover, zanubrutinib is similar to acalabrutinib, with less activity against TEC and ITK. The preliminary phase 1 results suggest that zanubrutinib has clinical activity and the drug is well tolerated in patients with B-cell lymphoid malignancies. Recent clinical trials have found it to demonstrate excellent efficacy and good tolerability in patients with chronic lymphocytic leukemia (CLL), Waldenstrom macroglobulinemia (WM) and mantle cell lymphoma (MCL). In recent phase 3 studies, zanubrutinib was compared with ibrutinib in patients with relapsed/refractory (R/R) MW and RR CLL. In both trials, zanubrutinib was found to demonstrate clinically meaningful advantages in safety and tolerability over ibrutinib; in particular, it was associated with a lower risk of atrial fibrillation/flutter and major bleeding events. In the recent SEQUOIA study, comparing zanubrutinib with bendamustine and rituximab (BR) in patients with previously untreated CLL, zanubrutinib significantly improved progression-free survival versus BR, with an acceptable safety profile consistent with previous studies. Zanubrutinib also demonstrated good activity and tolerability in patients with R/R MCL, marginal zone lymphoma and follicular lymphoma. Trials examining the efficacy and safety of the combination of zanubrutinib with obinutuzumab venetoclax and other drugs are ongoing. This review summarizes the clinical efficacy and safety of zanubrutinib in lymphoid malignancies.

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Case Report: Dual Inhibition of HDAC and BTK for Diffuse Large B-Cell Lymphoma After Failure to CD19-Targeted CAR-T Therapy

Cited by 5 publications

References 31 publications

Case report: CD19-directed CAR-T cell therapy combined with BTK inhibitor and PD-1 antibody against secondary central nervous system lymphoma

Case report: CD19-directed CAR-T cell therapy combined with BTK inhibitor and PD-1 antibody against secondary central nervous system lymphoma

Treatment strategies for relapse after CAR T-cell therapy in B cell lymphoma

Zanubrutinib for the treatment of lymphoid malignancies: Current status and future directions

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