Nonmyeloablative allogeneic transplantation achieves clinical and molecular remission in cutaneous T-cell lymphoma

Abstract

The majority of patients with refractory, advanced-stage mycosis fungoides (MF) or Sézary syndrome (SS) have a life expectancy of <5 years. Here, we report a phase 2 study of a novel nonmyeloablative allogeneic transplantation strategy tailored for this patient population. This study has completed the enrollment, and 35 patients (13 MF, 22 SS) have undergone transplant as planned. The majority (80%) of the patients had stage IV disease and received multiple previous systemic therapies. All patients had active disease at the time of conditioning using total skin electron beam therapy, total lymphoid irradiation, and antithymocyte globulin, and received allograft infusion as outpatients. Cyclosporine or tacrolimus and mycophenolate mofetil were used for graft-versus-host disease (GVHD) prophylaxis. Patients tolerated the transplant well, with 1- and 2-year nonrelapse mortality of 3% and 14%, respectively. The day +180 cumulative incidence of grade 2 to 4 acute GVHD was 16%, and the 2-year incidence of moderate/severe chronic GVHD was 32%. With a median posttransplant follow-up of 5.4 years, the 2-, 3-, and 5-year overall survival rates were 68%, 62%, and 56%. Using high-throughput sequencing of the T-cell receptor for minimal residual disease monitoring, we observed that 43% achieved molecular remission, which was associated with a lower incidence of disease progression or relapse (9% vs 87%; P = .02). Our study also showed that patients who were aged ≥65 years at the time of allotransplant had similar clinical outcomes compared with younger patients. Thus, we have developed an alternative and potentially curative nonmyeloablative allogeneic transplant regimen for patients with advanced stage MF/SS. This trial was registered at www.clinicaltrials.gov as #NCT00896493.

Conflict of interest statement

Conflict-of-interest disclosure: A.R. received research funding from Pharmacyclics. D.M. served on the advisory board for Adaptive Biotechnologies, AlloGene, Janssen, Juno-Celgene-BMS, Kite-Gilead, Miltenyi Biotec, Novartis, Pharmacyclics, and Precision Bioscience; and received research funding from Adaptive Biotechnologies, Becton Dickinson, Genentech, Isolexis, Kite-Gilead, Novartis, and Pharmacyclics. R.S.N. consulted for Amgen, Kuur, Magenta Therapeutics, and Jazz; and owns stocks of Magenta Therapeutics and BioEclipse Therapeutics. M.K. consulted for Kyowa-Kirin and Seattle Genetics. Y.H.K. served on the advisory board for Galderma, Innate, Kyocera, Corvus, and Seattle Genetics; and received research funding from Corvus, Eisai, Elorac, Galderma, Innate, Kyowa Kirin, Portola, Soligenix, and Trillium Pharmaceuticals. The remaining authors declare no competing financial interests.

© 2020 by The American Society of Hematology.

Figures

Graphical abstract

Figure 1.

Cumulative incidences of GVHD. Cumulative incidences of acute GVHD grades 2 to 4 (blue dotted line in A), grade 3 to 4 (red solid line in A), and moderate/severe chronic GVHD (B).

Figure 2.

Survival posttransplant. Kaplan-Meier estimates of OS (blue solid line), PFS (red solid line), and EFS (light green dotted line).

Figure 3.

Incidence of disease progression/relapse posttransplant. Cumulative incidence of disease progression/relapse in patients who achieve molecular remission (red dotted line) and in patients who had MRD (blue solid line). (A) All patients. (B) Patients in CR.