Haematologica (Mar 2023)

Characteristics and clinical outcomes of patients with acute myeloid leukemia with inv(3)(q21q26.2) or t(3;3)(q21;q26.2)

  • Guillaume Richard-Carpentier,
  • Caitlin R. Rausch,
  • Koji Sasaki,
  • Danielle Hammond,
  • Kiyomi Morita,
  • Koichi Takahashi,
  • Guilin Tang,
  • Rashmi Kanagal-Shamanna,
  • Kapil Bhalla,
  • Courtney D. Dinardo,
  • Gautam Borthakur,
  • Naveen Pemmaraju,
  • Elizabeth J. Shpall,
  • Amin Alousi,
  • Naval G. Daver,
  • Guillermo Garcia-Manero,
  • Marina Y. Konopleva,
  • Farhad Ravandi,
  • Hagop M. Kantarjian,
  • Tapan M. Kadia

DOI
https://doi.org/10.3324/haematol.2022.282030
Journal volume & issue
Vol. 108, no. 9

Abstract

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Acute myeloid leukemia (AML) with inv(3)(q21q26.2)/t(3;3)(q21;q26.2) has a very poor prognosis. Determinants of clinical outcomes and optimal treatment remain uncertain. We retrospectively reviewed 108 cases of AML with inv(3)/t(3;3) and evaluated clinicopathological characteristics and clinical outcomes: 53 newly diagnosed (ND) AML and 55 relapsed/refractory (R/R) AML. Median age was 55 years. White blood cell (WBC) count ≥20x109/L and platelet count ≥140x109/L was observed in 25% and 32% of ND patients, respectively. Anomalies involving chromosome 7 were identified in 56% of patients. The most frequently mutated genes were SF3B1, PTPN11, NRAS, KRAS and ASXL1. In ND patients, the composite complete remission (CRc) rate was 46% overall; 46% with high-intensity treatments and 47% with lowintensity treatments. The 30-day mortality was 14% and 0%, with high- and low-intensity treatment, respectively. In R/R patients, the CRc rate was 14%. Venetoclax based-regimens were associated with a CRc rate of 33%. The 3-year overall survival (OS) was 8.8% and 7.1% in ND and R/R patients, respectively. The 3-year cumulative incidence of relapse was 81.7% overall. Older age, high WBC, high peripheral blast count, secondary AML and KRAS, ASXL1, DNMT3A mutations were associated with worse OS in univariable analyses. The 5-year OS rates were 44% and 6% with or without hematopoietic stem cell transplantation in CR1, respectively. AML with inv(3)/t(3;3) is associated with low CR rates, very high risk of relapse and dismal long-term survival. Intensive chemotherapy and hy pomethylating agents provide similar rates of remission and patients achieving CR benefit from hematopoietic stem cell transplantation in first CR.