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Interferon administration reduces relapse after transplant in leukaemia patients

Hospital Healthcare Europe
15 December, 2021  

Interferon given prior to transplantation in high-risk acute myeloid leukaemia appeared to reduce the rate of disease recurrence.

Provision of interferon before transplantation to patients with acute myeloid leukaemia (AML) either not in remission or treatment-resistant, led to reduction in the rate of disease relapse after six months and which was sustained for at least 12 months after the transplant. 

This was the finding from a clinical trial conducted by a team from the Division of Haematology-Oncology, University of Michigan, US.1 Among patients with AML, the most potent therapy is haematopoietic stem cell transplantation (HSCT). Nevertheless, HSCT is deemed to be more toxic than both chemo- and immunotherapy and thus considered as an option for those in whom the estimated survival time and quality of life exceed other treatment.2 The rationale for HSCT after chemo- or radiotherapy is that the donor T cells, either alone or possibly in combination with other immune cells, help to eliminate any residual leukaemia cells in the recipient; and this response is known as graft-versus-host leukaemia.3 However, despite the expectation that HSCT is curative, relapse is common with up to 50% of patients experiencing a relapse and 2-year survival rates are below 20%.4 

For the present study, the US team conducted a Phase I/II trial to evaluate the safety and efficacy of subcutaneous, long-acting formulation of type 1 interferon in reducing relapse among high-risk AML patients, i.e., those not in remission, when they received HSCT. The interferon was administered the day before HSCT followed by three further
injections every 14 days. In the first part of the trial, the team determined the maximum tolerated dose of interferon which was 180 micrograms. For the second part of the trial,
the primary efficacy endpoint was the cumulative incidence of relapse at six months post-HSCT. The team also considered overall survival (OS) and leukaemia-free survival (LFS) as secondary outcomes.

Findings

A total of 36 patients with a median age of 60 years (39% female) were included in the full study although data for 31 were reported in the Phase II analysis. The cumulative incidence of relapse was 39% (95% CI 24–58%) which was sustained at 1-year. The OS in Phase II was 55% at 6-months and 33% after 2-years. In addition, LFS was 48% at 6-months and 28% after 2-years and there were no differences in either OS or LFS by age or donor type. The authors also reported no apparent safety concerns from using interferon. 

Commenting on their findings, the authors noted that with prior studies indicating a relapse incidence of approximately 60%, interferon use appeared to reduce relapse in high-risk patients with AML after HSCT by 20%. Furthermore, OS also appeared to be improved at 33% compared to previously reported figures of between 14 and 26%, although this would require confirmation in further studies. They concluded that their data would require validation in a prospective randomised trial.

References

  1. Magenau JM et al. Type-1 Interferon to Prevent Leukemia Relapse after Allogeneic Transplantation. Blood Adv 2021: doi: 10.1182/bloodadvances. 2021004908.
  2. Takami A. Hematopoietic stem cell transplantation for acute myeloid leukemia. Int J Hematol 2018;107:513–18.
  3. Sweeney C, Vyas P. The graft-versus-leukemia effect in AML. Front Oncol 2019;9:1217.
  4. Ruatenberg C et al. Relapse of acute myeloid leukemia after allogenic stem cell transplantation: prevention, detection and treatment. Int J Mol Sci 2019;20(1):228.
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