GIMEMA AML1310 trial of risk-adapted, MRD-directed therapy for young adults with newly diagnosed acute myeloid leukemia

• Published in: Blood Vol. 134; no. 12; pp. 935 - 945
• Main Authors: Venditti, Adriano, Piciocchi, Alfonso, Candoni, Anna, Melillo, Lorella, Calafiore, Valeria, Cairoli, Roberto, de Fabritiis, Paolo, Storti, Gabriella, Salutari, Prassede, Lanza, Francesco, Martinelli, Giovanni, Luppi, Mario, Mazza, Patrizio, Martelli, Maria Paola, Cuneo, Antonio, Albano, Francesco, Fabbiano, Francesco, Tafuri, Agostino, Chierichini, Anna, Tieghi, Alessia, Fracchiolla, Nicola Stefano, Capelli, Debora, Foà, Robin, Alati, Caterina, La Sala, Edoardo, Fazi, Paola, Vignetti, Marco, Maurillo, Luca, Buccisano, Francesco, Del Principe, Maria Ilaria, Irno-Consalvo, Maria, Ottone, Tiziana, Lavorgna, Serena, Voso, Maria Teresa, Lo-Coco, Francesco, Arcese, William, Amadori, Sergio
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 19-09-2019
• Subjects: Adolescent; Adult; Age Factors; Combined Modality Therapy; Consolidation Chemotherapy - methods; Cytogenetics; Female; Hematopoietic Stem Cell Transplantation - methods; Humans; Induction Chemotherapy - methods; Leukemia, Myeloid, Acute - diagnosis; Leukemia, Myeloid, Acute - genetics; Leukemia, Myeloid, Acute - pathology; Leukemia, Myeloid, Acute - therapy; Male; Middle Aged; Molecular Targeted Therapy - methods; Neoplasm, Residual; Precision Medicine - methods; Prognosis; Remission Induction - methods; Risk Assessment; Young Adult
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.2018886960

We designed a trial in which postremission therapy of young patients with de novo acute myeloid leukemia (AML) was decided combining cytogenetics/genetics and postconsolidation 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 (AlloSCT). Intermediate-risk patients (IR) were to receive AuSCT or AlloSCT depending on the postconsolidation levels of MRD. Three hundred sixty-one of 500 patients (72%) achieved a complete remission, 342/361 completed the consolidation phase and were treatment allocated: 165 (48%) to AlloSCT (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 AlloSCT 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, and 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, AlloSCT prolongs OS and DFS to equal those of the FR category. Using all the available sources of stem cells, AlloSCT was delivered to 71% of the candidates.This trial was registered at www.clinicaltrials.gov as #NCT01452646 and EudraCT as #2010-023809-36.
•A risk-adapted, MRD-driven transplant strategy is a feasible approach for the treatment of younger adults with AML.•Pretransplant MRD positivity should not contraindicate delivery of an allogeneic stem cell transplant.
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