PMID- 36757706 OWN - NLM STAT- MEDLINE DCOM- 20230424 LR - 20240210 IS - 2374-2445 (Electronic) IS - 2374-2437 (Print) IS - 2374-2437 (Linking) VI - 9 IP - 4 DP - 2023 Apr 1 TI - Allogeneic Hematopoietic Cell Transplantation vs Standard Consolidation Chemotherapy in Patients With Intermediate-Risk Acute Myeloid Leukemia: A Randomized Clinical Trial. PG - 519-526 LID - 10.1001/jamaoncol.2022.7605 [doi] AB - IMPORTANCE: The ideal postremission strategy in intermediate-risk acute myeloid leukemia (AML) in first complete remission (CR) has been a matter of debate. OBJECTIVE: To explore the optimal therapy for patients with intermediate-risk AML after first complete remission. DESIGN, SETTINGS, AND PARTICIPANTS: This investigator-initiated, open-label, 2-armed, phase 3 randomized clinical trial assessed patients at 16 hospitals in Germany from February 2, 2011, until July 1, 2018. Key eligibility criteria included cytogenetically defined intermediate-risk AML according to Medical Research Council classification, first CR or CR with incomplete blood cell count recovery after conventional induction therapy, age of 18 to 60 years, and availability of a human leukocyte antigen (HLA)-matched sibling or unrelated donor. A detailed statistical analysis plan was written and finalized on July 7, 2020. Data were exported for analysis on April 13, 2021. INTERVENTIONS: Patients were randomized 1:1 to receive allogeneic hematopoietic cell transplantation (HCT) or high-dose cytarabine for consolidation and salvage HCT only in case of relapse. Strata for randomization included age (18-40 vs 41-60 years), NPM1 and CEBPA variation status, and donor type (unrelated vs related). MAIN OUTCOMES AND MEASURES: End points included overall-survival as the primary outcome and disease-free survival, cumulative incidence of relapse, treatment-related mortality, and quality of life measured according to the Medical Outcomes Study 36-Item Short-Form Health Survey as secondary outcomes. RESULTS: A total of 143 patients (mean [SD] age, 48.2 [9.8] years; 81 [57%] male) with AML who fulfilled the eligibility criteria were randomized. In the intention-to-treat analysis, the probability of survival at 2 years was 74% (95% CI, 62%-83%) after primary allogeneic HCT and 84% (95% CI, 73%-92%) after consolidation chemotherapy (P = .22). Disease-free survival after HCT at 2 years was 69% (95% CI, 57%-80%) compared with 40% (95% CI, 28%-53%) after consolidation chemotherapy (P = .001). Allogeneic HCT during the first CR was associated with a cumulative incidence of relapse at 2 years of 20% (95% CI, 13%-31%) compared with 58% (95% CI, 47%-71%; P < .001). Nonrelapse mortality at 2 years after primary allogeneic HCT was 9% (95% CI, 5%-19%) and 2% (95% CI, 0%-11%) after consolidation chemotherapy (P = .005). Similar outcomes were observed when analyses were confined to the 96 patients at intermediate risk according to the European Leukemia Network classification. Most importantly, all 41 patients relapsing after consolidation chemotherapy (36 hematologic, 4 molecular, and 1 extramedullary) proceeded to allogeneic HCT. No significant differences in health-related quality of life measures were observed between groups. CONCLUSIONS AND RELEVANCE: Primary allogeneic HCT during first CR was not associated with superior overall survival compared with consolidation chemotherapy in patients 60 years or younger with intermediate-risk AML during the first CR and an available donor. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01246752. FAU - Bornhauser, Martin AU - Bornhauser M AD - Medical Clinic I, University Hospital Carl Gustav Carus, Technical University Dresden, Dresden, Germany. AD - National Center for Tumor Diseases, Dresden, Germany. FAU - Schliemann, Christoph AU - Schliemann C AD - Department of Medicine A, University Hospital Munster, Munster, Germany. FAU - Schetelig, Johannes AU - Schetelig J AD - Medical Clinic I, University Hospital Carl Gustav Carus, Technical University Dresden, Dresden, Germany. FAU - Rollig, Christoph AU - Rollig C AD - Medical Clinic I, University Hospital Carl Gustav Carus, Technical University Dresden, Dresden, Germany. FAU - Kramer, Michael AU - Kramer M AD - Medical Clinic I, University Hospital Carl Gustav Carus, Technical University Dresden, Dresden, Germany. FAU - Glass, Bertram AU - Glass B AD - Helios Klinikum, Berlin, Germany. FAU - Platzbecker, Uwe AU - Platzbecker U AD - Department for Hematology and Cellular Therapy, University Hospital, Leipzig, Germany. FAU - Burchert, Andreas AU - Burchert A AD - Department for Hematology and Oncology, University Hospital, Marburg, Germany. FAU - Hanel, Mathias AU - Hanel M AD - Medical Clinic III, Klinikum Chemnitz, Chemnitz, Germany. FAU - Muller, Lutz P AU - Muller LP AD - Department of Internal Medicine IV, University Hospital Halle Martin Luther, University Halle-Wittenberg, Halle, Germany. FAU - Klein, Stefan AU - Klein S AD - University Hospital Mannheim, Mannheim, Germany. FAU - Bug, Gesine AU - Bug G AD - Department of Medicine, Hematology/Oncology, Goethe University Frankfurt, Frankfurt, Germany. FAU - Beelen, Dietrich AU - Beelen D AD - University Hospital Essen, Essen, Germany. FAU - Rosler, Wolf AU - Rosler W AD - Department of Hematology, Oncology, and Immunotherapy, University Hospital Erlangen, Erlangen, Germany. FAU - Schafer-Eckart, Kerstin AU - Schafer-Eckart K AD - Klinikum Nurnberg, Paracelsus Medizinische Privatuniversitat, Nuremberg, Germany. FAU - Schmid, Christoph AU - Schmid C AD - Department of Hematology, University Hospital Augsburg, Augsburg, Germany. FAU - Jost, Edgar AU - Jost E AD - University Hospital Aachen, Aachen, Germany. FAU - Lenz, Georg AU - Lenz G AD - Department of Medicine A, University Hospital Munster, Munster, Germany. FAU - Tischer, Johanna AU - Tischer J AD - University Hospital Munich-Grosshadern, Department of Internal Medicine III, Ludwig-Maximilian University Munich, Munich, Germany. FAU - Spiekermann, Karsten AU - Spiekermann K AD - University Hospital Munich-Grosshadern, Department of Internal Medicine III, Ludwig-Maximilian University Munich, Munich, Germany. FAU - Pfirrmann, Markus AU - Pfirrmann M AD - Institute for Medical Information Processing, Biometry, and Epidemiology, Ludwig-Maximilian University Munich, Munich, Germany. FAU - Serve, Hubert AU - Serve H AD - Department of Medicine, Hematology/Oncology, Goethe University Frankfurt, Frankfurt, Germany. FAU - Stolzel, Friedrich AU - Stolzel F AD - Medical Clinic I, University Hospital Carl Gustav Carus, Technical University Dresden, Dresden, Germany. FAU - Alakel, Nael AU - Alakel N AD - Medical Clinic I, University Hospital Carl Gustav Carus, Technical University Dresden, Dresden, Germany. FAU - Middeke, Jan Moritz AU - Middeke JM AD - Medical Clinic I, University Hospital Carl Gustav Carus, Technical University Dresden, Dresden, Germany. FAU - Thiede, Christian AU - Thiede C AD - Medical Clinic I, University Hospital Carl Gustav Carus, Technical University Dresden, Dresden, Germany. FAU - Ehninger, Gerhard AU - Ehninger G AD - Medical Clinic I, University Hospital Carl Gustav Carus, Technical University Dresden, Dresden, Germany. FAU - Berdel, Wolfgang E AU - Berdel WE AD - Department of Medicine A, University Hospital Munster, Munster, Germany. FAU - Stelljes, Matthias AU - Stelljes M AD - Department of Medicine A, University Hospital Munster, Munster, Germany. LA - eng SI - ClinicalTrials.gov/NCT01246752 PT - Clinical Trial, Phase III PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't PL - United States TA - JAMA Oncol JT - JAMA oncology JID - 101652861 SB - IM MH - Humans MH - Male MH - Middle Aged MH - Adolescent MH - Young Adult MH - Adult MH - Female MH - Consolidation Chemotherapy MH - Quality of Life MH - Transplantation, Homologous MH - *Hematopoietic Stem Cell Transplantation MH - Remission Induction MH - Recurrence MH - *Leukemia, Myeloid, Acute/drug therapy PMC - PMC9912165 COIS- Conflict of Interest Disclosures: Dr Bornhauser reported receiving personal fees from Jazz Pharmaceuticals and Gilead outside the submitted work. Dr Schetelig reported receiving grants from the German Ministry for Education and Research (Bundesministerium fur Bildung und Forschung) during the conduct of the study, personal fees from the AstraZeneca and BeiGene advisory boards, and lecture fees and personal fees from the Janssen, Bristol Myers Squibb (BMS), and AbbVie advisory boards outside the submitted work. Dr Rollig reported receiving grants from AbbVie, Novartis, and Pfizer and personal fees from Amgen, BMS, Jazz Pharmaceuticals, and Servier outside the submitted work. Dr Burchert reported receiving personal fees from Gilead, AOP Health, Incyte, and from Pfizer outside the submitted work. Dr Hanel reported receiving personal fees from Amgen, Bayer Vital, Celgene, Gilead, GlaxoSmithKline, Jazz Pharmaceuticals, Novartis, Roche, and Takeda outside the submitted work. Dr Muller reported receiving grants from Amgen Inc and personal fees from Celgene, Pfizer, and Neovii outside the submitted work. Dr Bug reported receiving personal fees from Novartis, Jazz Pharmaceuticals, Celgene/BMS, Pfizer, Gilead, and Novartis outside the submitted work. Dr Lenz reported receiving grants from Roche, Janssen, Agios, Aquinox, AstraZeneca, Gilead, Morphosys, and Bayer and personal fees from Roche, Janssen, AstraZeneca, BMS, Gilead, Sobi, ADC Therapeutics, AbbVie, Genmab, Morphosys, Incyte, Bayer, Karyopharm, Miltenyi, PentixaPharm, Novartis, Takeda, NanoString, and Constellation outside the submitted work. Dr Middeke reported receiving grants from Janssen, Novartis, and Jazz Pharmaceuticals and personal fees from AbbVie, AstraZeneca, Roche, Astellas, Jazz Pharmaceuticals, Janssen, and Novartis outside the submitted work. Dr Thiede reported part ownership in AgenDix GmbH during the conduct of the study and receiving personal fees from Novartis, Jazz Pharmaceuticals, Bayer, and Janssen outside the submitted work. No other disclosures were reported. EDAT- 2023/02/10 06:00 MHDA- 2023/04/24 06:42 PMCR- 2024/02/09 CRDT- 2023/02/09 11:33 PHST- 2023/04/24 06:42 [medline] PHST- 2023/02/10 06:00 [pubmed] PHST- 2023/02/09 11:33 [entrez] PHST- 2024/02/09 00:00 [pmc-release] AID - 2801295 [pii] AID - coi220096 [pii] AID - 10.1001/jamaoncol.2022.7605 [doi] PST - ppublish SO - JAMA Oncol. 2023 Apr 1;9(4):519-526. doi: 10.1001/jamaoncol.2022.7605.