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Therapy offers hope for durable remission in ATL
Graft-versus-adult T-cell leukemia/lymphoma-based therapy may be beneficial for patients with relapsed disease after allogeneic stem cell transplantation, according to results of a retrospective analysis.
Relapse of adult T-cell leukemia/lymphoma (ATL) presents clinical challenges among patients who have undergone allogeneic hematopoietic stem cell transplantation.
The current analysis included 35 patients who progressed or relapsed to persistent adult T-cell disease after a first transplantation.
The investigators culled data from three institutions in Japan from 1997 to 2010.
The initial intervention in 29 patients in the cohort was the withdrawal of immune suppressants. Complete remission was reported in two of those patients.
Among nine patients who received a combination of donor lymphocyte infusion and cytoreductive therapy, four achieved complete remission.
In six patients, immune suppressant therapy was discontinued before relapse. Three patients in this cohort with local recurrence initially were given local cytoreductive therapy that resulted in a complete response duration of 19 months or more.
Three patients experienced remission of more than 3 years. However, although the researchers said donor lymphocyte infusion-induced remission was durable, they also observed chronic graft-versus-host disease in all three of these patients.
After relapse, the 3-year OS rate for all 35 patients was 19.3%.
“The results of the present study suggest that induction of a graft-versus-ATL effect may be crucial to obtaining durable remission for ATL patients with relapse or progression after allogeneic hematopoietic stem cell transplantation,” the researchers concluded.
Perspective
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This study is an important accomplishment and should have an immediate impact on clinicians caring for patients with ATLL, as well as clinical and translational researchers. Overall, the most impressive finding is that immunotherapy — in this case, either by removing immunosuppressive medicines or simply by infusing more immune cells — yielded a significant number of partial and complete clinical remissions, whereas chemotherapy alone yielded none. The immunotherapy was not benign. It was generally accompanied by GVH, which could be mild or severe; still, the benefits were meaningful given the poor prognosis of these patients.
For primary oncologists, this study shows the potential for infrequent but significant long-term remissions induced by stem cell transplant (even after relapse) and the implicit importance of trying to get eligible patients to transplant. For our transplant physicians, this study highlights the potential benefits of donor lymphocyte infusion (DLI), which may immediately impact donor choice (eg, preferring incompletely matched allo- or haplo-donors over umbilical cord donors to maintain the DLI option if needed). For translational researchers, the benefits and risks of DLI suggest the need for developing “smart DLI” either by sorting/expanding/activating donor lymphocyte subsets or even by vaccinating the donor with peptides from human T-cell lymphotrophic virus proteins such as HBZ.
The implied superiority of immunotherapy over chemotherapy in the transplant setting also suggests the importance of pursuing immunotherapies that already appear promising in the non-transplant setting, such as the immunomodulator lenalidomide (Revlimid, Celgene), the anti-CCR4 antibody mogamulizumab (Poteligeo, Kyowa Hakko Kirin) and the anti-CD30 drug conjugate brentuximab vedotin (Adcetris, Seattle Genetics).