Abstract
The most common transcripts in chronic myeloid leukemia (CML) are e13a2 (b2a2) and e14a2 (b3a2). Previous studies suggest that e14a2 transcript predicts a faster and deeper response to imatinib compared to e13a2. However, the impact of the type of transcript on response after first-line therapy with a second generation tyrosine kinase inhibitor, nilotinib, is unknown.
We retrospectively analyzed in this observational study 79 newly diagnosed patients with chronic phase (CP) CML, treated with nilotinib 600 mg BID frontline in 3 centers between 2007 and 2017 inside or outside clinical trials.
Thirty-eight patients (48.1 %) expressed e14a2, 35 (44.3 %) e13a2 and 6 patients (7.6 %) both transcripts. Characteristics at diagnosis did not differ between patients expressing e14a2 or both transcripts and e13a2 with respectively a median age of 49 (range, 23-85) and 55 years (range, 19-78) (p=.13), a white blood cell count of 132.4 and 173.6 G/L (p=.15) and a platelet count of 529 and 404 G/L (p=.15). Relative risks of CP-CML at diagnosis were similar according to the Sokal score (p=.37), the Eutos Score (p=.98) or ELTS score (p=.39). Nilotinib was discontinued in 15 patients (18.9%) mostly for failure or progression (n=5) and intolerance (n=9) after a median time of 14.7 months (4.5-55.2). The proportion of patients e14a2 (or expressing both transcripts) and e13a2 achieving complete cytogenetic response at 6 months was respectively 95% and 85.2% (p=.155) whereas the rate of major molecular response at 1 year was 59% and 50% (p=.414). The probability to attain MR4.5 did not differ from the 2 groups (p=.264) with a median follow-up of 44.7 months (2.9-110.8).
This retrospective analysis confirms the excellent efficacy and tolerance of nilotinib frontline in CP CML, with similar results in terms of limitation of progression and deep molecular responses for both transcripts.
Nicolini: ARIAD: Honoraria, Speakers Bureau; Novartis: Consultancy, Honoraria, Research Funding, Speakers Bureau; BMS: Consultancy, Honoraria, Speakers Bureau; Incyte Biosciences: Honoraria, Speakers Bureau. Guyotat: Novartis: Research Funding, Speakers Bureau; BMS: Speakers Bureau.
