Allogeneic Hematopoietic Cell Transplantation in Patients ≤ 60 Years with Intermediate-Risk Acute Myeloid Leukemia in First Remission - Results of the Randomized Etal-1 Trial

• Published in: Blood 2021-11, Vol.138 (Supplement 1), p.173-173
• Main Authors: Bornhaeuser, Martin, Schliemann, Christoph, Schetelig, Johannes, Rollig, Christoph, Kramer, Michael, Glass, Bertram, Platzbecker, Uwe, Burchert, Andreas, Haenel, Mathias, Mueller, Lutz Peter, Klein, Stefan, Bug, Gesine, Beelen, Dietrich W., Roesler, Wolf, Schaefer-Eckart, Kerstin, Schmid, Christoph, Jost, Edgar, Lenz, Georg, Tischer, Johanna, Spiekermann, Karsten, Pfirrmann, Markus, Serve, Hubert, Stoelzel, Friedrich, Alakel, Nael, Ehninger, Gerhard, Berdel, Wolfgang E., Stelljes, Matthias
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2021-145167

Allogeneic hematopoietic cell transplantation (HCT) offers the highest chance for cure in patients with adverse-risk acute myeloid leukemia (AML) when performed in first remission (CR1). In contrast, patients in CR1 with favorable risk do not seem to benefit from allogeneic HCT due to the inherent risk of transplant-related mortality. Donor vs. no donor comparisons as well as prospective matched-pair analyses have suggested that allogeneic HCT performed in intermediate-risk AML may provide a higher probability of overall survival or relapse-free survival in patients ≤ 60 years of age with an acceptable risk for transplant-related mortality. On the other hand, many intermediate-risk patients relapsing after conventional chemotherapy may be successfully salvaged by allogeneic HCT. The role of allogeneic HCT in cytogenetically defined intermediate-risk AML patients in CR1 was addressed by a prospective randomized trial performed in 16 centers in Germany. Key inclusion criteria were: AML with intermediate-risk cytogenetics, first CR or CRi after conventional induction therapy, age of 18-60 years, and availability of an HLA-matched sibling or unrelated donor. For unrelated donors, a 9 out of 10 HLA allelic match was acceptable except for patients with an NPM1 mutation, for whom full 10/10 allele matching was required. Randomization was stratified according to age (< 40 vs. 40-60), NPM1/FLT3, and CEBP-alpha mutational status and unrelated vs. related donor availability. Endpoints included overall-survival as primary outcome and relapse-free survival (RFS), cumulative incidence of relapse, treatment-related mortality, and quality of life measured according to the short form (36) health status. From 2010 - 2018, 143 patients in CR1 were randomized into Arm A (n=76, allogeneic HCT) and Arm B (n=67, conventional consolidation and allo-HCT only in case of relapse). In July 2018, the trial was stopped prematurely due to slow accrual (143 out of 356 pts. randomized). Median age of the trial cohort was 51 years (range, 19-60), with 42% exhibiting an NPM1 and 25% a FLT3 mutation. A normal karyotype was reported in 84% of the included patients. All mentioned characteristics did not differ between both treatment arms. Sibling donors were available for 44 (31% of patients), matched unrelated donors for 99 (69%) patients. According to the intent-to-treat analysis, the probability of survival at 2 years was 71% (95% CI 60-81%) and 84% (95% CI 73-92%) in Arm A (Transplant) and