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Targeting CD38 with Daratumumab Plus Chemotherapy for Patients with Advanced-Stage Plasmablastoid Large B-Cell Lymphoma.

ABSTRACT: Plasmablastic lymphoma (PBL) is a rare and aggressive form of large B-cell lymphoma (LBCL) most commonly seen in the setting of chronic immunosuppression or autoimmune disease. The prognosis is poor and CHOP-like regimens often fail to produce durable remission; therefore, there is no established standard of care treatment. However, PBL demonstrates substantial morphologic and immunophenotypic overlap with multiple myeloma (MM), suggesting that MM therapeutics might prove useful in treating PBL. We studied the effects of treatment using the first-in-class monoclonal antibody directed against CD38, daratumumab, in combination with chemotherapy in seven patients with advanced-stage LBCL with plasmablastic features. Treatment was safe and well-tolerated. Among six evaluable patients, six patients had complete response after treatment, and four patients who met strict WHO criteria for PBL had durable response (12-31 months and ongoing).

SUBMITTER: Ryu YK

PROVIDER: S-EPMC9409851 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

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Targeting CD38 with Daratumumab Plus Chemotherapy for Patients with Advanced-Stage Plasmablastoid Large B-Cell Lymphoma.

Ryu Yun Kyoung YK Ricker Edd C EC Soderquist Craig R CR Francescone Mark A MA Lipsky Andrew H AH Amengual Jennifer E JE

Journal of clinical medicine 20220822 16

Plasmablastic lymphoma (PBL) is a rare and aggressive form of large B-cell lymphoma (LBCL) most commonly seen in the setting of chronic immunosuppression or autoimmune disease. The prognosis is poor and CHOP-like regimens often fail to produce durable remission; therefore, there is no established standard of care treatment. However, PBL demonstrates substantial morphologic and immunophenotypic overlap with multiple myeloma (MM), suggesting that MM therapeutics might prove useful in treating PBL. ...[more]

PMID: 36013165

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Project description:IntroductionRelapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL) has poor clinical outcomes when treated with conventional salvage chemotherapy. Monotherapy using zanubrutinib, a selective Bruton's tyrosine kinase (BTK) inhibitor, has achieved modest antitumor effect in R/R DLBCL. Here we aimed to evaluate the efficacy and safety of zanubrutinib plus salvage chemotherapy in R/R DLBCL patients.MethodsWe retrospectively reviewed R/R DLBCL patients who were administered with zanubrutinib plus salvage chemotherapy in our center between January, 2019 and December, 2021. Targeted panel sequencing of 11 lymphoma-related genes was performed on 8 patients with poor responses to zanubrutinib-based chemotherapy.Results27 R/R DLBCL patients were enrolled. Median age at this study was 59 years (range, 15-72). The best overall response rate (ORR) was 74.1% and complete remission rate was 33.3%. With a median follow-up of 11 months (range, 1-17), the median progression-free survival (PFS) was 8.1 months, and the overall survival (OS) was not achieved. The most common grade-3/4 adverse events were neutropenia (70.4%), thrombocytopenia (66.7%), and febrile neutropenia (33.3%). In multivariate analysis, early treatment and overall response after chemotherapy were independent favorable prognostic factors for PFS. Overall response after chemotherapy was an independent favorable factor for OS. Among the 8 patients with poor response to zanubrutinib-based treatment, the majority of patients had NOTCH2 mutations (n=8, 100%) and TP53 mutations (n=7, 87.5%). However, these patients achieved an ORR of 75% at 3 months after CD19-CAR-T cell therapy (including 4 cases of complete remission and 2 cases of partial remission). With a median follow-up of 9 months from CAR-T cell infusion (range, 1-16 months), the median PFS was 14.5 months, and the median OS was not reached.ConclusionWith high efficacy and manageable tolerability, zanubrutinib plus salvage chemotherapy may be a potential treatment option for R/R DLBCL. CAR-T cell therapy may be a priority strategy for these poor responders to BTKi-based treatment.

Dataset Information

Targeting CD38 with Daratumumab Plus Chemotherapy for Patients with Advanced-Stage Plasmablastoid Large B-Cell Lymphoma.

Publications

Targeting CD38 with Daratumumab Plus Chemotherapy for Patients with Advanced-Stage Plasmablastoid Large B-Cell Lymphoma.

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