AI Article Synopsis

  • Angioimmunoblastic T-cell lymphoma (AITL) is a type of cancer with a poor response to traditional chemotherapy, featuring a low median survival rate and common relapses.
  • A study tested a combination of the drug 5-azacytidine and nivolumab (an anti-PD-1 therapy) in nine patients with AITL, finding it to be well-tolerated and effective, with a 78% overall response rate.
  • These promising results suggest that this treatment combination may be a safer and more effective option, warranting further research to establish its efficacy in larger trials.

Article Abstract

Introduction: Angioimmunoblastic T-cell lymphoma (AITL) is a peripheral T-cell lymphoma characterized by a T follicular helper cell phenotype expressing PD-1 (programmed cell death-1). AITL exhibits a poor response to conventional chemotherapy, with a median 5-year overall survival of 44% and a progression-free survival of 32%. Relapse is common, resulting in a median overall survival of 6 months. Recurrent mutations are detected in genes regulating DNA methylation, including TET2, DNMT3A, and IDH2 variants, along with the prevalent RHOA G17V mutation. In this context, patients treated with the hypomethylating agent 5-azacytidine achieved overall response and complete response rates of 75% and 41%, respectively. We hypothesized that targeted therapies combining anti-PD-1 checkpoint blockers with hypomethylating agents could be efficient in AITL patients and less toxic than standard chemotherapy.

Methods: Here, we report the efficacy of a regimen combining 5-azacytidine and nivolumab in nine relapsed or refractory AITL patients.

Results: This regimen was well-tolerated, especially in elderly patients. The overall response rate was 78%, including four partial responses (44%) and three complete responses (33%). Allogeneic hematopoietic stem cell transplantation was performed in two patients who reached complete response.

Discussion: These preliminary favorable results may serve as a basis for further investigation in prospective studies.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11231067PMC
http://dx.doi.org/10.3389/fimmu.2024.1410638DOI Listing

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Article Synopsis
  • Angioimmunoblastic T-cell lymphoma (AITL) is a type of cancer with a poor response to traditional chemotherapy, featuring a low median survival rate and common relapses.
  • A study tested a combination of the drug 5-azacytidine and nivolumab (an anti-PD-1 therapy) in nine patients with AITL, finding it to be well-tolerated and effective, with a 78% overall response rate.
  • These promising results suggest that this treatment combination may be a safer and more effective option, warranting further research to establish its efficacy in larger trials.
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Unlabelled: Acute myeloid leukemia (AML) is a heterogeneous malignancy of the blood primarily treated with intensive chemotherapy. The allogeneic T-cell antileukemic activity via donor lymphocyte infusions and stem cell transplantation suggests a potential role for checkpoint blockade therapy in AML. While clinical trials employing these treatments have fallen short of expected results, a deeper exploration into the functional states of T cells in AML could bridge this knowledge gap.

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January 2024

Division of Hematology-Oncology, Cancer and Blood Disease Institute, Children's Hospital Los Angeles, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA 90027, USA.

Improvements in survival have been made over the past two decades for childhood acute myeloid leukemia (AML), but the approximately 40% of patients who relapse continue to have poor outcomes. A combination of checkpoint-inhibitor nivolumab and azacitidine has demonstrated improvements in median survival in adults with AML. This phase I/II study with nivolumab and azacitidine in children with relapsed/refractory AML (NCT03825367) was conducted through the Therapeutic Advances in Childhood Leukemia & Lymphoma consortium.

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