Azacitidine, lenalidomide and donor lymphocyte infusions for relapse of myelodysplastic syndrome, acute myeloid leukemia and chronic myelomonocytic leukemia after allogeneic transplant: the Azalena-Trial
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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. / Schroeder, Thomas; Stelljes, Matthias; Christopeit, Maximilian; Esseling, Eva; Scheid, Christoph; Mikesch, Jan-Henrik; Rautenberg, Christina; Jäger, Paul; Cadeddu, Ron-Patrick; Drusenheimer, Nadja; Holtick, Udo; Klein, Stefan; Trenschel, Rudolf; Haas, Rainer; Germing, Ulrich; Kröger, Nicolaus; Kobbe, Guido.
in: HAEMATOLOGICA, Jahrgang 108, Nr. 11, 01.11.2023, S. 3001-3010.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Azacitidine, lenalidomide and donor lymphocyte infusions for relapse of myelodysplastic syndrome, acute myeloid leukemia and chronic myelomonocytic leukemia after allogeneic transplant: the Azalena-Trial
AU - Schroeder, Thomas
AU - Stelljes, Matthias
AU - Christopeit, Maximilian
AU - Esseling, Eva
AU - Scheid, Christoph
AU - Mikesch, Jan-Henrik
AU - Rautenberg, Christina
AU - Jäger, Paul
AU - Cadeddu, Ron-Patrick
AU - Drusenheimer, Nadja
AU - Holtick, Udo
AU - Klein, Stefan
AU - Trenschel, Rudolf
AU - Haas, Rainer
AU - Germing, Ulrich
AU - Kröger, Nicolaus
AU - Kobbe, Guido
PY - 2023/11/1
Y1 - 2023/11/1
N2 - 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).
AB - 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).
KW - Adult
KW - Humans
KW - Azacitidine/therapeutic use
KW - Lenalidomide
KW - Leukemia, Myelomonocytic, Chronic/therapy
KW - Lymphocyte Transfusion/adverse effects
KW - Myelodysplastic Syndromes/pathology
KW - Leukemia, Myeloid, Acute
KW - Transplantation, Homologous/adverse effects
KW - Chronic Disease
KW - Graft vs Host Disease/diagnosis
KW - T-Lymphocytes/pathology
KW - Recurrence
KW - Hematopoietic Stem Cell Transplantation/adverse effects
U2 - 10.3324/haematol.2022.282570
DO - 10.3324/haematol.2022.282570
M3 - SCORING: Journal article
C2 - 37259567
VL - 108
SP - 3001
EP - 3010
JO - HAEMATOLOGICA
JF - HAEMATOLOGICA
SN - 0390-6078
IS - 11
ER -