Azacitidine, lenalidomide and donor lymphocyte infusions for relapse of myelodysplastic syndrome, acute myeloid leukemia and chronic myelomonocytic leukemia after allogeneic transplant: the Azalena-Trial
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
Affiliations
Thomas Schroeder
Department of Hematology and Stem Cell Transplantation, West German Cancer Center Essen, University Hospital Essen, Essen, Germany; Department of Hematology, Oncology and Clinical Immunology, University Hospital Duesseldorf, Medical Faculty, Heinrich Heine – University, Duesseldorf
Matthias Stelljes
Department of Medicine A, Hematology and Oncology, University of Muenster, Muenster
Maximilian Christopeit
University Hospital Hamburg-Eppendorf, Clinic for Stem Cell Transplantation, Hamburg
Eva Esseling
Department of Medicine A, Hematology and Oncology, University of Muenster, Muenster
Christoph Scheid
Department I of Internal Medicine, Medical Faculty and University Hospital, University of Cologne, Cologne
Jan-Henrik Mikesch
Department of Medicine A, Hematology and Oncology, University of Muenster, Muenster
Christina Rautenberg
Department of Hematology and Stem Cell Transplantation, West German Cancer Center Essen, University Hospital Essen, Essen
Paul Jäger
Department of Hematology, Oncology and Clinical Immunology, University Hospital Duesseldorf, Medical Faculty, Heinrich Heine – University, Duesseldorf
Ron-Patrick Cadeddu
Department of Hematology, Oncology and Clinical Immunology, University Hospital Duesseldorf, Medical Faculty, Heinrich Heine – University, Duesseldorf
Nadja Drusenheimer
Coordination Center for Clinical Trials, University Hospital Duesseldorf, Medical Faculty, Heinrich Heine – University, Duesseldorf
Udo Holtick
Department I of Internal Medicine, Medical Faculty and University Hospital, University of Cologne, Cologne
Stefan Klein
Department of Hematology and Oncology, University Hospital Mannheim, Mannheim
Rudolf Trenschel
Department of Hematology and Stem Cell Transplantation, West German Cancer Center Essen, University Hospital Essen, Essen
Rainer Haas
Department of Hematology, Oncology and Clinical Immunology, University Hospital Duesseldorf, Medical Faculty, Heinrich Heine – University, Duesseldorf
Ulrich Germing
Department of Hematology, Oncology and Clinical Immunology, University Hospital Duesseldorf, Medical Faculty, Heinrich Heine – University, Duesseldorf
Nicolaus Kröger
University Hospital Hamburg-Eppendorf, Clinic for Stem Cell Transplantation, Hamburg
Guido Kobbe
Department of Hematology, Oncology and Clinical Immunology, University Hospital Duesseldorf, Medical Faculty, Heinrich Heine – University, Duesseldorf
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).
