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. 2024 May 31;14(1):91.
doi: 10.1038/s41408-024-01069-9.

Imatinib with intensive chemotherapy in AML with t(9;22)(q34.1;q11.2)/BCR::ABL1. A DATAML registry study

Camille Gondran #  1 , Pierre-Yves Dumas #  2   3   4 , Emilie Bérard  5   6 , Audrey Bidet  7 , Eric Delabesse  6   8 , Suzanne Tavitian  1 , Thibaut Leguay  2 , Françoise Huguet  1 , Cécile Borel  1 , Edouard Forcade  2   3 , François Vergez  8 , Jean-Philippe Vial  7 , Jean Baptiste Rieu  8 , Nicolas Lechevalier  7 , Isabelle Luquet  8 , Alban Canali  8 , Emilie Klein  7 , Audrey Sarry  1 , Anne-Charlotte de Grande  2 , Arnaud Pigneux  2   3 , Christian Récher #  9   10 , Laetitia Largeaud #  6   8 , Sarah Bertoli #  1   6
Affiliations

Imatinib with intensive chemotherapy in AML with t(9;22)(q34.1;q11.2)/BCR::ABL1. A DATAML registry study

Camille Gondran et al. Blood Cancer J. .

Abstract

Acute myeloid leukemia (AML) with t(9;22) (q34.1; q11.2)/BCR::ABL1, a distinct entity within the group of AML with defining genetic abnormalities, belong to the adverse-risk group of the 2022 ELN classification. However, there is little data on outcome since the era of tyrosine kinase inhibitors. Among 5819 AML cases included in the DATAML registry, 20 patients with de novo BCR::ABL1+AML (0.3%) were identified. Eighteen patients treated with standard induction chemotherapy were analyzed in this study. Imatinib was added to chemotherapy in 16 patients. The female-to-male ratio was 1.25 and median age was 54 years. The t(9;22) translocation was the sole chromosomal abnormality in 12 patients. Main gene mutations detected by NGS were ASXL1, RUNX1 and NPM1. Compared with patients with myeloid blast phase of chronic myeloid leukemia (CML-BP), de novo BCR::ABL1+AML had higher WBC, fewer additional chromosomal abnormalities, lower CD36 or CD7 expression and no ABL1 mutations. Seventeen patients (94.4%) achieved complete remission (CR) or CR with incomplete hematologic recovery. Twelve patients were allografted in first remission. With a median follow-up of 6.3 years, the median OS was not reached and 2-year OS was 77% (95% CI: 50-91). Four out of five patients who were not transplanted did not relapse. Comparison of BCR::ABL1+AML, CML-BP, 2017 ELN intermediate (n = 643) and adverse-risk patients (n = 863) showed that patients with BCR::ABL1+AML had a significant better outcome than intermediate and adverse-risk patients. BCR::ABL1+AML patients treated with imatinib and intensive chemotherapy should not be included in the adverse-risk group of current AML classifications.

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Conflict of interest statement

SB declares a consulting or advisory role with Abbvie, Astellas, BMS-Celgene, Jazz Pharmaceuticals as well as Servier and received travel grants from Abbvie and Pfizer. CR declares a consulting or advisory role with Abbvie, Amgen, Astellas, BMS, Boehringer, Jazz Pharmaceuticals as well as Servier, received research funding from Abbvie, Amgen, Astellas, BMS, Iqvia and Jazz Pharmaceuticals, and support for attending meetings and/or travel from Abbvie, Novartis and Servier. AP declares a consulting or advisory role with Astellas, BMS, Servier, Abbvie, Gilead, Jazz Pharmaceuticals, Novartis, Pfizer, received research funding from Astellas, BMS, Roche, Servier and support for attending meetings and/or travel from Servier, Abbvie. FV: research grants from Pierre Fabre and Roche; advisor for Astellas and Amgen. FH: consultancy Novartis, Pfizer, Incyte, honoraria Amgen, Servier; Isabelle Luquet: advisory role for Jazz Pharmaceuticals. All other authors declare no competing interests.

Figures

Fig. 1
Fig. 1. Chromosomal abnormalities and mutations.
Additional chromosomal abnormalities (A) and mutational profile (B) in patients with de novo BCR::ABL1+AML or CML-BP. A de novo BCR::ABL1+AML in blue (n = 20), CML-BP in yellow (n = 29).
Fig. 2
Fig. 2. Immunophenotyping.
A Immunophenotypic classification: HSC-L hematopoietic stem cells-like, MPP-L multipotent progenitors-like, CMP-L common myeloid progenitors-like, GMP-L granulocyte–monocyte progenitors, GP-L granulocyte progenitors-like, MP-L monocyte progenitors-like. B CD7 expression in CML-BP, de novo BCR::ABL1+AML or BCR::ABL1 negative AML. C CD36 expression in CML-BP, de novo BCR::ABL1+AML or BCR::ABL1 negative AML (AML). D, E Hierarchical clustering based on frequencies of hematopoietic stem and progenitor subpopulations. F, G CD133+ LMPP and CD133+ GMP frequencies in CML-BP and de novo BCR::ABL1+AML.
Fig. 3
Fig. 3. Survival curves in patients with de novo BCR::ABL1+AML, CML-BP, ELN 2017 intermediate or high-risk patients.
A Event-free survival (EFS). B Relapse-free survival (RFS). C Overall survival (OS).
See this image and copyright information in PMC

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