Allogeneic Transplantation in Patients With Advanced Cutaneous T-Cell Lymphomas

The Lancet

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• This prospective trial of 99 patients with advanced-stage cutaneous T-cell lymphomas in full or partial remission reported significantly longer progression-free survival among patients who underwent allogeneic haematopoietic stem cell transplantation (HSCT) compared with those who underwent treatment other than HSCT (9 months vs 3 months). In addition, significantly fewer patients experienced disease relapse in the HSCT group than in the non-HSCT group. Excluding graft-versus-host disease, the most common serious adverse event in both groups was infections.
• Patients with advanced-stage cutaneous T-cell lymphomas in partial or full remission who received allogeneic HSCT experienced significantly longer progression-free survival compared with those who received non-HSCT treatment.

–  Lillian Sun, MD

Abstract

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.

The Lancet

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

Lancet 2023 Apr 24;[EPub Ahead of Print], A de Masson, M Beylot-Barry, C Ram-Wolff, JB Mear, S Dalle, M d'Incan, S Ingen-Housz-Oro, C Orvain, J Abraham, O Dereure, A Charbonnier, J Cornillon, C Longvert, S Barete, S Boulinguez, E Wierzbicka-Hainaut, F Aubin, MT Rubio, M Bernard, A Schmidt-Tanguy, R Houot, A Pham-Ledard, D Michonneau, P Brice, H Labussière-Wallet, JD Bouaziz, F Grange, H Moins-Teisserenc, K Jondeau, L Michel, S Mourah, M Battistella, E Daguindau, M Loschi, A Picard, N Franck, N Maillard, A Huynh, S Nguyen, A Marçais, G Chaby, P Ceballos, Y Le Corre, S Maury, JO Bay, H Adamski, E Bachy, E Forcade, G Socié, M Bagot, S Chevret, R Peffault de Latour