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

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 impro...

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Main Authors: Schroeder, Thomas (Author) , Stelljes, Matthias (Author) , Christopeit, Maximilian (Author) , Esseling, Eva (Author) , Scheid, Christoph (Author) , Mikesch, Jan-Henrik (Author) , Rautenberg, Christina (Author) , Jäger, Paul (Author) , Cadeddu, Ron-Patrick (Author) , Drusenheimer, Nadja (Author) , Holtick, Udo (Author) , Klein, Stefan (Author) , Trenschel, Rudolf (Author) , Haas, Rainer (Author) , Germing, Ulrich (Author) , Kröger, Nicolaus (Author) , Kobbe, Guido (Author)
Format: Article (Journal)
Language:English
Published: November, 2023
In: Haematologica
Year: 2023, Volume: 108, Issue: 11, Pages: 3001-3010
ISSN:1592-8721
DOI:10.3324/haematol.2022.282570
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.3324/haematol.2022.282570
Verlag, kostenfrei, Volltext: https://haematologica.org/article/view/haematol.2022.282570
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Author Notes: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 and Guido Kobbe
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Summary: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).
Item Description:Gesehen am 13.08.2024
Physical Description:Online Resource
ISSN:1592-8721
DOI:10.3324/haematol.2022.282570

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