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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 progressionfree 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. [ABSTRACT FROM AUTHOR]

Competing Interests: Nicolas Stocker reports lecture honoraria from AbbVie and AstraZeneca and congress invitations from BeiGene, Janssen, and Novartis, all outside the submitted work. Eolia Brissot reports research funding, honorarium, speaker's fees, and travel expenses from Novartis, Astellas, Alexion, Jazz Pharmaceuticals, Gilead, MSD, Keocyt, Amgen, Beigen, Pierre Fabre, Pfizer, Celgene/BMS, and Sanofi, all outside the submitted work. Rémy Duléry reports research funding from Ligue Contre le Cancer, Arthur Sachs, Monahan Foundation, Servier Foundation, Philippe Foundation, and DCP AP‐HP, honoraria from Novartis and Takeda, and nonfinancial support from Sanofi and Kite Pharma/Gilead, all outside the submitted work. Zoé Van de Wyngaert reported consulting fees from Janssen‐Cilag, BMS, and Sanofi. Antoine Capes reports honoraria from Takeda. Harry Sokol reports lecture fee, board membership, or consultancy from Amgen, Fresenius, IPSEN, Actial, Astellas, Danone, THAC, Biose, BiomX, Eligo, Immusmol, Adare, Nestle, Ferring, MSD, Bledina, Pfizer, Biocodex, BMS, Bromatech, Gilead, Janssen, Mayoli, Roche, Sanofi, Servier, Takeda, and Abbvie, has stocks from Enterome Bioscience, and is co‐founder of Exeliom Biosciences. Mohamad Mohty reports grants and lecture honoraria from Janssen, Sanofi, Maat Pharma, and JAZZ Pharmaceuticals, lecture honoraria from Celgene, Amgen, BMS, Takeda, and Pfizer, and grants from Roche, all outside the submitted work. Florent Malard reports lecture honoraria from Therakos/Mallinckrodt, BMS, MSD, Sanofi, Novartis, Astra Zeneca, and JAZZ Pharmaceuticals, all outside the submitted work. The other authors declare no competing financial interests.

Individuals with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) have a high risk of developing other malignancies (OMs). The development of OMs may be associated with the advanced age of CLL/SLL patients, presence of a tumor-promoting microenvironment, immune alterations inherent to CLL/SLL, or chemotherapy. Importantly, the occurrence of OMs following frontline fludarabine, cyclophosphamide and rituximab (FCR) treatment is associated with a reduction in the overall survival (OS). This retrospective study included 108 CLL/SLL patients treated with FCR immunochemotherapy, as a first line treatment. With a median follow-up of 94.9 (6-222) months, 31% developed an OM or more, within a median of 61.8 months post-FCR initiation. The most common OMs were non-melanoma skin cancers (7%), Richter's syndrome (RS) (7%), myelodysplastic syndromes (6%), prostate cancer (4%), and acute myeloid leukemia (3%). Patients with OMs had shorter survival compared to those without (104.0 versus 149.0 months, P=0.02), with RS having the worst OS at 4.8 months (P<0.0001), followed by therapy-related myeloid neoplasia (t-MN) at 14.5 months. Although the onset of OMs in patients with CLL/SLL was observed after considerable delays, its impact on survival is significant in the immunochemotherapy era, necessitating a better understanding of these patterns to improve CLL/SLL management and guide future treatment strategies., Competing Interests: NS reports lecture honoraria from AbbVie, Astra Zeneca, and Janssen, all outside of the submitted work. FM reports lecture honoraria from Therakos/Mallinckrodt, Janssen, Biocodex, Sanofi, Jazz Pharmaceuticals, Gilead, and Astellas, all outside of the submitted work. TA reports lecture and/or consulting honoraria from Biotest and Amgen, all outside of the submitted work. MM reports grants and lecture honoraria from Janssen, Sanofi, Maat Pharma, and JAZZ Pharmaceuticals; lecture honoraria from Celgene, Amgen, BMS, Takeda, and Pfizer; and grants from Roche, all outside the submitted work. EB reports lecture honoraria from Novartis, Astellas, Alexion, Jazz Pharmaceuticals, Gilead/Kyte, MSD, Keocyt, Amgen, Pierre Fabre, BeiGene, all outside the submitted work. The other authors declare no competing financial interests.