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

• Verfasst von: Schroeder, Thomas [VerfasserIn]
• Verfasst von: Stelljes, Matthias [VerfasserIn]
• Verfasst von: Christopeit, Maximilian [VerfasserIn]
• Verfasst von: Esseling, Eva [VerfasserIn]
• Verfasst von: Scheid, Christoph [VerfasserIn]
• Verfasst von: Mikesch, Jan-Henrik [VerfasserIn]
• Verfasst von: Rautenberg, Christina [VerfasserIn]
• Verfasst von: Jäger, Paul [VerfasserIn]
• Verfasst von: Cadeddu, Ron-Patrick [VerfasserIn]
• Verfasst von: Drusenheimer, Nadja [VerfasserIn]
• Verfasst von: Holtick, Udo [VerfasserIn]
• Verfasst von: Klein, Stefan [VerfasserIn]
• Verfasst von: Trenschel, Rudolf [VerfasserIn]
• Verfasst von: Haas, Rainer [VerfasserIn]
• Verfasst von: Germing, Ulrich [VerfasserIn]
• Verfasst von: Kröger, Nicolaus [VerfasserIn]
• Verfasst von: Kobbe, Guido [VerfasserIn]
• Titel: Azacitidine, lenalidomide and donor lymphocyte infusions for relapse of myelodysplastic syndrome, acute myeloid leukemia and chronic myelomonocytic leukemia after allogeneic transplant
• Titelzusatz: the Azalena-Trial
• Verf.angabe: 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
• E-Jahr: 2023
• Jahr: November, 2023
• Umfang: 10 S.
• Illustrationen: Illustrationen
• Fussnoten: Gesehen am 13.08.2024
• Titel Quelle: Enthalten in: Haematologica
• Ort Quelle: Pavia : Ferrata Storti Foundation, 2014
• Jahr Quelle: 2023
• Band/Heft Quelle: 108(2023), 11, Seite 3001-3010
• ISSN Quelle: 1592-8721
• DOI: doi:10.3324/haematol.2022.282570
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1898509999

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).