Treatment-free remission in chronic myeloid leukemia with rare ABL1 gene fusions: Real-life study from the French CML group Fi-LMC

Abstract

Tyrosine kinase inhibitors of the BCR::ABL1 oncoprotein can be stopped without subsequent molecular relapse or major safety concerns in 40-80 % of adult patients with P210^BCR::ABL1 positive chronic myeloid leukemia with sustained deep molecular responses. In contrast, ending treatment in patients with rare rearrangements located outside the major BCR region or within the exon 3 of ABL1 remains to be explored. Twenty-four patients with chronic phase disease and diverse uncommon BCR::ABL1 transcripts who obtained sustained molecular residual disease negativity and stopped therapy in a real-life setting for various reasons were retrospectively evaluated for treatment-free remission determinants. Six patients relapsed after a median time of 6 months (range; 3-49), relapse being defined as a rise in molecular residual disease above the 3-log threshold. Treatment-free remission probabilities at 12 and 60 months were 83.3 % (95 % CI: 68.4-98.2 %) and 70.6 % (95 % CI: 49.5-91.6), respectively. The type of BCR::ABL1 transcript was the only relevant baseline factor associated with durable treatment-free remission and patients with fusions lacking exon a2 sequences had the best outcome. To conclude, treatment-free remission is a reasonably achievable goal in patients with rare ABL1 fusion transcripts. Our results pave the way for recommendations in clinical practice. Nevertheless, further research is needed to determine which patients have highest chances to reach deep molecular response levels and become free from therapy and to decipher the biological impact of the different molecular rearrangements of BCR::ABL1 on treatment-free remission.

Keywords: Chronic myeloid leukemia – rare transcripts – tyrosine kinase inhibitor- treatment-free remission.