KEY TAKEAWAYS
- The study aimed to test the efficiency and toxicity of targeted therapies combining anti-PD-1 checkpoint blockers with hypomethylating agents in pts with AITL.
- The regimen was well-tolerated, with a 78% response rate, and formed a basis for further investigation.
Angioimmunoblastic T-cell lymphoma (AITL) is a peripheral T-cell lymphoma characterized by a phenotype expressing PD-1 (programmed cell death-1) in T follicular helper cells. In traditional chemotherapy regimens, a poor response has been exhibited by (pts) with AITL. A median 5-year overall survival (OS) of 44% and a progression-free survival (PFS) of 32%. Relapse is common, resulting in a median OS of 6 months.
Recurrent mutations are identified in genes responsible for regulation of DNA methylation, including TET2, DNMT3A, and IDH2 variants, along with the prevalent RHOA G17V mutation. In this context, pts treated with the hypomethylating agent 5-azacytidine (Aza) achieved OS and complete response (CR) rates of 75% and 41%, respectively.
Laure Ricard and the team aimed to explore whether the targeted therapies by combining anti-PD-1 checkpoint blockers and hypomethylating agents could be efficient in pts with AITL and less toxic than standard chemotherapy.
Researchers conducted a monocentric and retrospective study in which pts received 5-Aza at 75 mg/m2 subcutaneously for 7 consecutive days every 28 days and nivolumab (Nivo) at a dose of 3 mg/kg every 14 days (5-Aza/Nivo) until progression or achieving a CR. Eligible pts then underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT).
As per the standardized recommendations, response to treatment was assessed clinically and using positron emission tomography-computed tomography scans (PET-scanner) every 2 cycles. Expert pathologists from the national program “Lymphopath” confirmed the AITL diagnosis based on the World Health Organization 2016 classification. DNA sequencing was performed using deep next-generation sequencing (NGS) with a 47-gene capture panel.
This study was performed in accordance with the Good Clinical Practice protocol and the principles of the Declaration of Helsinki.
The study concluded by demonstrating that the regimen were well-tolerated, predominantly in pts with older age. The OS rate was 78%, including 4 partial responses (PR) (44%) and 3 CRs (33%). The allo-HSCT was performed in 2 pts who reached a complete response.
The study provided preliminary favorable results that may serve as a basis for further investigation in prospective studies.
No financial support was received for this study.
Source: https://pubmed.ncbi.nlm.nih.gov/38983865/
Ricard L, Cervera P, Stocker N, et al. (2024). “A combination of 5-azacytidine and nivolumab is a potentially effective rescue therapy in relapsed/refractory AITL.” Front Immunol. 2024 Jun 25;15:1410638. doi: 10.3389/fimmu.2024.1410638. PMID: 38983865; PMCID: PMC11231067.
