Cytogenetic Features Linked with ‘Very High Risk' of AML Relapse

Acute myeloid leukemia (AML) with inv(3)(q21q26.2) or t(3;3)(q21;q26.2) is associated with low rates of complete remission (CR), a “very high risk” of relapse and “dismal” long-term survival, according to a recent study.

Guillaume Richard-Carpentier, MD, of the University of Toronto Princess Margaret Cancer Centre and the MD Anderson Cancer Center and colleagues conducted the research because AML with inv(3)(q21q26.2) or t(3;3)(q21;q26.2) has a “very poor prognosis” and “determinants of clinical outcomes and optimal treatment remain uncertain.”

They retrospectively reviewed data from 108 patients who had AML with inv(3)(q21q26.2) or t(3;3)(q21;q26.2). The group included 53 patients who were newly diagnosed and 55 who had relapsed or refractory disease. Dr. Richard-Carpentier and colleagues evaluated clinicopathological characteristics and clinical outcomes in the patients, who had a median age of 55 years.

Of the newly diagnosed patients, 25% had a white blood cell count ≥20 × 10⁹/L and 32% had a platelet count of ≥140 × 10⁹/L. More than half (56%) of patients had anomalies involving chromosome seven. SF3B1, PTPN11, NRAS, KRAS, and ASXL1 were the most frequently mutated genes.

The overall composite CR rate was 46% in newly diagnosed patients. The composite CR rate was 46% in those who received high-intensity treatments and 47% in those who received low-intensity treatments.

In patients who received high-intensity treatments, the 30-day mortality rate was 14%, while it was 0% in those who received low-intensity treatments. In patients with relapsed or refractory AML, the composite CR rate was 14%, but venetoclax-based regimens were associated with a composite CR rate of 33%.

Newly diagnosed patients had a three-year overall survival (OS) rate of 8.8%. The three-year OS rate was 7.1% in those with relapsed or refractory disease. The three-year cumulative incidence of relapse was 81.7% overall.

“Older age, high [white blood cell count], high peripheral blast count, secondary AML and KRAS, ASXL1, DNMT3A mutations were associated with worse OS in univariable analyses,” Dr. Richard-Carpentier and colleagues wrote.

In patients who received hematopoietic stem-cell transplantation (HSCT) in their first CR, the five-year OS rate was 44%, while it was 6% in those who did not receive HSCT in their first CR.

“AML with inv(3)/t(3;3) is associated with low CR rates, very high risk of relapse and dismal long-term survival,” Dr. Richard-Carpentier and colleagues wrote. “Intensive chemotherapy and [hypomethylating agents] provide similar rates of remission and patients achieving CR benefit from HSCT in [their first CR].”

Reference

Richard-Carpentier G, Rausch CR, Sasaki K, et al. Characteristics and clinical outcomes of patients with acute myeloid leukemia with inv(3)(q21q26.2) or t(3;3)(q21;q26.2). Haematologica. 2023. doi:10.3324/haematol.2022.282030