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GIMEMA AML1310 TRIAL OF RISK-ADAPTED, MRD-DIRECTED THERAPY FOR YOUNG ADULTS WITH NEWLY DIAGNOSED ACUTE MYELOID LEUKEMIA

Adriano Venditti, Alfonso Piciocchi, Anna Candoni, Lorella Melillo, Valeria Calafiore, Roberto Cairoli, Paolo de Fabritiis, Gabriella Storti, Prassede Salutari, Francesco Lanza, Giovanni Martinelli, Mario Luppi, Patrizio Mazza, Maria Paola Martelli, Antonio Cuneo, Francesco Albano, Francesco Fabbiano, Agostino Tafuri, Anna Chierichini, Alessia Tieghi, Nicola Stefano Fracchiolla, Debora Capelli, Robin Foà, Caterina Alati, Edoardo La Sala, Paola Fazi, Marco Vignetti, Luca Maurillo, Francesco Buccisano, Maria Ilaria Del Principe, Maria Irno-Consalvo, Tiziana Ottone, Serena Lavorgna, Maria Teresa Voso, Francesco Lo Coco, William Arcese and Sergio Amadori

Key Points

  • A risk-adapted, MRD-driven transplant strategy is a feasible approach for the treatment of younger adults with AML

  • Pre-transplant MRD positivity should not be a contraindication to the delivery of allogenic stem cell transplant in younger adults with AML

Abstract

We designed a trial in which post-remission therapy of young patients with de novo AML was decided combining cytogenetics/genetics and post-consolidation levels of minimal residual disease (MRD). After induction and consolidation, favorable-risk patients (FR) were to receive autologous stem cell transplant (AuSCT) and poor-risk patients (PR) allogeneic stem cell transplant (ASCT). Intermediate-risk patients (IR) were to receive AuSCT or ASCT depending on the post-consolidation levels of MRD. ASCT was to be delivered whatever the source of stem cells. Three hundred-61/500 patients (72%) achieved a CR, 342/361 completed the consolidation phase and were treatment allocated: 165 (48%) to ASCT (122 PR, 43 IR MRD-positive) plus 23 rescued after salvage therapy, for a total of 188 candidates; 150 (44%) to AuSCT (115 FR, 35 IR MRD-negative) plus 27 IR patients (8%) with no leukemia-associated phenotype, for a total of 177 candidates. Overall, 110/177 (62%) and 130/188 (71%) AuSCT or ASCT candidates received it, respectively. Two-year overall (OS) and disease-free survival (DFS) of the whole series was 56% and 54%, respectively. Two-year OS and DFS were 74% and 61% in the FR category, 42% and 45% in the PR category, 79% and 61% in the IR MRD-negative category, 70% and 67% in the IR MRD-positive category. In conclusion, AuSCT may still have a role in FR and IR MRD-negative categories. In the IR MRD-positive category, ASCT prolongs OS and DFS to equal those of the FR category. Using all the available sources of stem cells, ASCT was delivered to 71% of the candidates. EudraCT number (2010-023809-36); ClinicalTrials.Gov Identifier (NCT01452646).

  • Submitted November 29, 2018.
  • Revision received August 8, 2019.
  • Accepted August 1, 2019.