Azacitidine, lenalidomide and donor lymphocyte infusions for relapse of myelodysplastic syndrome, acute myeloid leukemia and chronic myelomonocytic leukemia after allogeneic transplant: the Azalena-Trial.

Abstract

Azacitidine (Aza) combined with donor lymphocyte infusions (DLI) is an established treatment for relapse of myeloid malignancies after allogeneic transplantation. Based on its immunomodulatory and anti-leukemic properties we considered Lenalidomide (Lena) to act synergistically with Aza/DLI to improve outcome. We, therefore, prospectively investigated tolerability and efficacy of this combination as first salvage therapy for adults with post-transplant relapse of acute myeloid leukemia, myelodysplastic syndromes and chronic myelomonocytic leukemia. Patients were scheduled for eight cycles Aza (75 mg/m2 day 1-7), Lena (2.5 or 5 mg, days 1-21) and up to three DLI with increasing T-cell dosages (0.5×106-1.5×107 cells/kg). Primary endpoint was safety, while secondary endpoints included response, graft-versus-host disease (GvHD) and overall survival (OS). Fifty patients with molecular (52%) or hematological (48%) relapse of myelodysplastic syndromes (n=24), acute myeloid leukemia (n=23) or chronic myelomonocytic leukemia (n=3) received a median of seven (range, 1-8) cycles including 14 patients with 2.5 mg and 36 with 5 mg Lena daily dosage. Concomitantly, 34 patients (68%) received at least one DLI. Overall response rate was 56% and 25 patients (50%) achieved complete remission being durable in 80%. Median OS was 21 months and 1-year OS rate 65% with no impact of type of or time to relapse and Lena dosages. Treatment was well tolerated indicated by febrile neutropenia being the only grade ≥3 non-hematologic adverse event in >10% of patients and modest acute (grade 2-4 24%) and chronic (moderate/severe 28%) GvHD incidences. In summary, Lena can be safely added to Aza/DLI without excess of GvHD and toxicity. Its significant anti-leukemic activity suggests that this combination is a novel salvage option for post-transplant relapse (clinicaltrials gov. Identifier: NCT02472691).

• Authors: Thomas Schroeder, Matthias Stelljes, Maximilian Christopeit, Eva Esseling, Christoph Scheid, Jan-Henrik Mikesch, Christina Rautenberg, Paul Jäger, Ron-Patrick Cadeddu, Nadja Drusenheimer, Udo Holtick, Stefan Klein, Rudolf Trenschel, Rainer Haas, Ulrich Germing, Nicolaus Kröger, Guido Kobbe
• Journal: Haematologica (Haematologica) Vol. 108 Issue 11 Pg. 3001-3010 (11 01 2023) ISSN: 1592-8721 [Electronic] Italy
• PMID: 37259567 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Azacitidine
• Lenalidomide

Topics

• Adult
• Humans
• Azacitidine (therapeutic use)
• Lenalidomide
• Leukemia, Myelomonocytic, Chronic (therapy, complications)
• Lymphocyte Transfusion (adverse effects)
• Myelodysplastic Syndromes (pathology)
• Leukemia, Myeloid, Acute
• Transplantation, Homologous (adverse effects)
• Chronic Disease
• Graft vs Host Disease (diagnosis, etiology, drug therapy)
• T-Lymphocytes (pathology)
• Recurrence
• Hematopoietic Stem Cell Transplantation (adverse effects)