SOHO State of the Art Updates and Next Questions: Withdrawal Syndrome after Tyrosine Kinase Inhibitor Discontinuation in Patients with Chronic Myeloid Leukemia in the Russian Prospective Study RU-SKI

Abstract Introduction We aimed to characterize withdrawal syndrome (WS) and evaluate factors associated with its development in the prospective clinical study RU-SKI in chronic myeloid leukemia (CML) patients with deep molecular response (DMR) who discontinued tyrosine kinase inhibitor (TKI) therapy. Patients and methods In total, 98 adult patients with CML chronic phase, TKI therapy ≥ 3 years, and DMR (BCR-ABL ≤ 0.01%) ≥ 2 years were enrolled and observed without treatment. WS was defined as newly observed or worsening musculoskeletal pain after TKI cessation. Results WS symptoms were found in 41 (42%) of 98 patients with a median (Me) time of observation of 25 months (range of 12–42 months). WS grades 1–2 and grade 3 were observed in 39 (95%) and in 2 (5%) patients, respectively. The Ме duration of WS was 5 months (range of 1–25 months). WS was resolved in 37 (90%) patients. Anti-inflammatory therapy was used in 21 (51%) patients. Older age (p = 0.039) and longer TKI therapy (p = 0.001) were associated with WS. The 2-month landmark analysis found no association of WS development and the rate of molecular relapses. Conclusion In total, 42% of the patients experienced WS after TKI therapy discontinuation in the RU-SKI study. Physicians should be warned about the possibility of WS development, and patients of older age and with longer TKI treatment need special attention.