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Optimizing checkpoint inhibitors therapy for relapsed or progressive classic Hodgkin lymphoma by multiplex immunohistochemistry of the tumor microenvironment.

ABSTRACT: Immune checkpoint-blocking antibodies have therapeutic activity against relapsed or progressive classic Hodgkin lymphoma (cHL), but Hodgkin Reed-Sternberg cells can develop resistance to this therapy via multiple mechanisms. To improve the efficacy of immune checkpoint blockade, we need a more precise understanding of the immune escape mechanisms active in individual cHL patients, and this requires a detailed characterization of immune cell populations in the tumor microenvironment. These cell-cell interactions can now be studied by multiplex immunohistochemistry coupled to digital image analysis. This method should allow the identification of actionable target molecules mediating resistance to immune checkpoint inhibitors in individual cHL patients, thereby favoring the implementation of personalized therapies.

SUBMITTER: Carbone A

PROVIDER: S-EPMC6558469 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Optimizing checkpoint inhibitors therapy for relapsed or progressive classic Hodgkin lymphoma by multiplex immunohistochemistry of the tumor microenvironment.

Carbone Antonino A Gloghini Annunziata A Pruneri Giancarlo G Dolcetti Riccardo R

Cancer medicine 20190508 6

Immune checkpoint-blocking antibodies have therapeutic activity against relapsed or progressive classic Hodgkin lymphoma (cHL), but Hodgkin Reed-Sternberg cells can develop resistance to this therapy via multiple mechanisms. To improve the efficacy of immune checkpoint blockade, we need a more precise understanding of the immune escape mechanisms active in individual cHL patients, and this requires a detailed characterization of immune cell populations in the tumor microenvironment. These cell-c ...[more]

PMID: 31070022

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Project description:On May 17, 2016, after an expedited priority review, the U.S. Food and Drug Administration granted accelerated approval to nivolumab for the treatment of patients with classical Hodgkin lymphoma (cHL) that has relapsed or progressed after autologous hematopoietic stem cell transplantation (HSCT) and post-transplantation brentuximab vedotin (BV). Nivolumab in cHL had been granted breakthrough therapy designation. Accelerated approval was based on two single-arm, multicenter trials in adults with cHL. In 95 patients with relapsed or progressive cHL after autologous HSCT and post-transplantation BV, nivolumab, dosed at 3 mg/kg intravenously every 2 weeks, produced a 65% (95% confidence interval: 55%-75%) objective response rate (58% partial remission, 7% complete remission). The estimated median duration of response was 8.7 months, with 4.6-month median follow-up for response duration. The median time to response was 2.1 (range: 0.7-5.7) months. Among 263 patients with cHL treated with nivolumab, 21% reported serious adverse reactions (ARs). The most common all-grade ARs (reported in ?20%) were fatigue, upper respiratory tract infection, cough, pyrexia, diarrhea, elevated transaminases, and cytopenias. Infusion-related reaction and hypothyroidism or thyroiditis occurred in >10% of patients; other immune-mediated ARs, occurring in 1%-5%, included rash, pneumonitis, hepatitis, hyperthyroidism, and colitis. A new Warning and Precaution was issued for complications of allogeneic HSCT after nivolumab, including severe or hyperacute graft-versus-host disease, other immune-mediated ARs, and transplant-related mortality. Continued approval for the cHL indication may be contingent upon verification of clinical benefit in a randomized trial. The Oncologist 2017;22:585-591 IMPLICATIONS FOR PRACTICE: Based on response rate and duration in single-arm studies, nivolumab is a new treatment option for patients with classical Hodgkin lymphoma (cHL) that has relapsed or progressed despite autologous hematopoietic stem cell transplantation (HSCT) and brentuximab vedotin. This was the first U.S. Food and Drug Administration marketing application for a programmed cell death 1 inhibitor in hematologic malignancies. The use of immune checkpoint blockade in cHL represents a new treatment paradigm. The safety of allogeneic HSCT after nivolumab requires further evaluation, as does the safety of nivolumab after allogeneic HSCT.

Dataset Information

Optimizing checkpoint inhibitors therapy for relapsed or progressive classic Hodgkin lymphoma by multiplex immunohistochemistry of the tumor microenvironment.

Publications

Optimizing checkpoint inhibitors therapy for relapsed or progressive classic Hodgkin lymphoma by multiplex immunohistochemistry of the tumor microenvironment.

Similar Datasets

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