Allogeneic transplantation in advanced cutaneous T-cell lymphomas (CUTALLO): a propensity score matched controlled prospective study.

Background: Advanced-stage cutaneous T-cell lymphomas (CTCLs) are rare, usually refractory, and fatal diseases. Case series have suggested that allogeneic haematopoietic stem cell transplantation (HSCT) might improve the prognosis of advanced-stage CTCLs. The objective of this study was to investigate the effect of allogeneic HSCT compared with non-HSCT therapy on the outcome of individuals with advanced-stage CTCLs.
Methods: In this prospective, multicentre, matched controlled trial, conducted at 30 hospitals, participants with advanced CTCLs were allocated treatment: if they had an available compatible related donor they were assigned to allogeneic HSCT, or if not they were allocated to non-allogeneic HSCT therapy. Key inclusion criteria were participants aged 18-70 years, with advanced stage mycosis fungoides or Sézary syndrome, and at least one poor prognostic criteria. Participants were excluded if they were not in complete or partial remission of the disease. Propensity score 1:1 matching with replacement (ie, that each participant treated with HSCT was matched to the participant with the closest propensity score treated with non-HSCT therapy, even if they had already been matched) was used to handle confounding factors, with the balance of covariate distribution between HSCT and non-HSCT groups assessed using standardised mean differences. The primary endpoint was progression-free survival in the matched intention-to-treat population. This trial is registered with ClinicalTrials.gov (NCT02520908), and is currently active but not recruiting.
Findings: From June 1, 2016, to March 3, 2022, total of 99 participants were enrolled at 17 centres in France. Participants with a sibling or matched unrelated donor were assigned to allogeneic HSCT (HSCT group, n=55 [56%]) and participants without a donor were assigned to non-allogeneic HSCT treatment (non-HSCT group, n=44 [44%]). The median follow-up among survivors was 12·6 months (IQR 11·0-35·2). In the HSCT group, 51 participants (93%) were 1:1 matched to participants from the non-HSCT group. In the intention-to-treat analysis, median progression-free survival was significantly longer in the HSCT group (9·0 months [95% CI 6·6-30·5]) than in the non-HSCT group (3·0 months [2·0-6·3]), with a hazard ratio of 0·38 (95% CI 0·21-0·69; p<0·0001). In the per-protocol population, 40 participants (78%) in the HSCT group had 101 serious events and 29 participants (67%) in the non-HSCT group had 70 serious adverse events. The most common serious adverse event other than graft-versus-host disease in both groups was infections, occurring in 30 participants (59%) in the HSCT group and in 19 participants (44%) in the non-HSCT group.
Interpretation: Allogeneic HSCT was associated with significantly longer progression-free survival in participants with advanced-stage CTCLs. These results indicate that allogeneic HSCT treatment should be made available to individuals with high-risk, advanced-stage mycosis fungoides or Sézary syndrome who achieve pre-transplant disease remission.
Funding: French Ministry of Health, National Cancer Institute, Programme Hospitalier de Recherche Clinique en Cancérologie.
Competing Interests: Declaration of interests AdM reports research funding from Innate, Almirall, and Kyowa Kirin; travel expenses from Kyowa Kirin, Recordati Rare Diseases and Orphan Europe, and Janssen-Cilag; and fees from Takeda. MB-B reports consultancy at Kyowa Kirin and Recordati; and research funding from Celgene and Roche. SD reports institutional grants from Bristol Myers Squibb and Merck Sharp & Dohme. SI-H-O reports consultancy for Takeda and Recordati. CO reports honoraria from Novartis. JA reports honoraria from Roche and Janssen. OD reports consultancy from Bristol Myers Squibb, Kyowa Kirin, Merck, Sharpe & Dohme, Novartis, Pierre Fabre, Recordati Rare Diseases, Sanofi, and Sun Pharma; honoraria from Bristol Myers Squibb, Kyowa Kirin, LeoPharma, Merck, Sharpe & Dohme, Novartis, Pierre Fabre, Recordati Rare Diseases, Sanofi, and Sun Pharma; registration to meetings from Bristol Myers Squibb, Kyowa Kirin, LeoPharma, Merck, Sharpe & Dohme, Novartis, and Pierre Fabre; grants from Pierre Fabre; research funding from Kyowa Kirin, Novartis, and Pierre Fabre; and travel expenses from Bristol Myers Squibb, Janssen, Kyowa Kirin, LeoPharma, Merck, Sharpe & Dohme, Novartis, Pierre Fabre, and Sanofi. SBa reports consultancy at Amgen and Blueprint Medicines; and honoraria from Novartis, Leo Laboratories, and AbbVie. EW-H reports consultancy at Novartis, Bristol Myers Squibb, Pierre Fabre, BluePrint, Sun Pharma, AbbVie, and Sanofi; research funding from AbbVie; and honoraria from Bristol Myers Squibb, Novartis, AbbVie, Sanofi, and Pierre Fabre. FA reports consultancy at AbbVie, Almirall, Amgen, Bristol Myers Squibb, Janssen-Cilag, Leo, Merck Sharp & Dohme, Novartis, Pierre Fabre, Sanofi, and Union Chimique Belge; honoraria from AbbVie, Almirall, Amgen, Bristol Myers Squibb, Janssen-Cilag, Leo, Merck Sharp & Dohme, Novartis, Pierre Fabre, Sanofi, and Union Chimique Belge; and research funding from Galderma, Janssen, and Pfizer. RH reports honoraria from Kite and Gilead, Novartis, Incyte, Janssen, Merck Sharp & Dohme, Takeda, and Roche; and consultancy at Kite and Gilead, Novartis, Bristol Myers Squibb and Celgene, ADC Therapeutics, Incyte, and Miltenyi. AP-L reports honoraria from Bristol Myers Squibb and Novartis; and travel accommodation and meeting participation from Kyowa Kirin, Recordati, Novartis, and Bristol Myers Squibb. DM reports honoraria from Novartis, Incyte, CSL Behring, and Jazz Pharmaceuticals. J-DB reports being on a speaker or advisory board member for Boehringer-Ingelheim, Janssen, Novartis, Union Chimique Belge, Leo, AbbVie, Eli Lilly, Pfizer, Sanofi, and Almirall. FG reports consultancy at Recordati Rare Disease, Kyowa Kirin, Novartis, Pierre Fabre, Bristol Myers Squibb, and Merck Sharp & Dohme. HM-T reports consultancy at Innate; and research funding from Kyowa Kirin. SMo reports honoraria from Novartis, Pierre Fabre, Roche and Biocartis; and research funding from Novartis and Bristol Myers Squibb. MBat reports consultancy at Bristol Myers Squibb and Quantum Genomics; honoraria from Innate, Kyowa Kirin, Takeda, Meccellis Biotech, Cerba Research, and Sanofi; research funding from Kyowa Kirin; and grants from Takeda. ED reports grants from Pfizer and Mallinckrodt; and consultancy at Swedish Orphan Biovitrum. ML reports honoraria from Novartis, Pfizer, Alexion Pharmaceuticals, Sandoz, Novartis, Sanofi, Swedish Orphan Biovitrum, Gilead, and Bristol Myers Squibb. AP reports consultancy and honoraria from Novartis, Pierre-Fabre, Bristol Myers Squibb, Merck Sharp & Dohme, and Sun Pharma. AH reports consultancy at Novartis, Astellas, Jazz Pharmaceuticals, and Pfizer; and honoraria from Novartis, Astellas, Jazz Pharmaceuticals, and Pfizer. YLC reports consultancy at Novartis, Merck Sharp & Dohme, Bristol Myers Squibb, and Pierre Fabre Oncologie; and honoraria from Novartis, Leo, AbbVie, Pfizer, and Pierre Fabre Oncologie. EF reports participation in advisory board at Gilead, GSK, and Sanofi; speakers bureau from Novartis and Alexion; honoraria from Novartis; and travel grants from Gilead, Merck Sharp & Dohme, Jazz Pharmaceuticals, and Novartis. GS reports consultancy at Novartis and Alexion Pharmaceuticals; honoraria from Novartis, Incyte, and Alexion Pharmaceuticals; and research funding from Alexion Pharmaceuticals. RPdL reports consultancy at Novartis, Pfizer, Amgen, Alexion Pharmaceuticals, Apellis Pharmaceuticals, and Swedish Orphan Biovitrum; honoraria from Novartis, Pfizer, Amgen, Alexion Pharmaceuticals, Apellis Pharmaceuticals, and Swedish Orphan Biovitrum; research funding from Novartis, Pfizer, Amgen, and Alexion Pharmaceuticals; and grants from Alexion Pharmaceuticals, Amgen, Novartis, and Pfizer. All other authors declare no competing interests.
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