TY - JOUR

T1 - Withdrawal Syndrome After Tyrosine Kinase Inhibitor Discontinuation in Patients With Chronic Myeloid Leukemia in the Russian Prospective Study RU-SKI

AU - Chelysheva, Ekaterina

AU - Shukhov, Oleg

AU - Bykova, Anastasiya

AU - Nemchenko, Irina

AU - Gusarova, Galina

AU - Tsyba, Nikolay

AU - Julhakyan, Hunan

AU - Shuvaev, Vasiliy

AU - Fominykh, Mikhail

AU - Martynkevich, Irina

AU - Ionova, Tatyana

AU - Turkina, Anna

PY - 2020/5

Y1 - 2020/5

N2 - We aimed to characterize withdrawal syndrome (WS) and evaluate factors associated with its development in the prospective clinical study RU-SKI in patients with chronic myeloid leukemia with deep molecular response who discontinued tyrosine kinase inhibitor (TKI) therapy. In total, 98 adult patients with chronic myeloid leukemia chronic phase, TKI therapy ≥ 3 years, and deep molecular response (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. WS symptoms were found in 41 (42%) of 98 patients with a median time of observation of 25 months (range, 12-42 months). WS grades 1 to 2 and grade 3 were observed in 39 (95%) and in 2 (5%) patients, respectively. The median duration of WS was 5 months (range, 1-25 months). WS was resolved in 37 (90%) patients. Anti-inflammatory therapy was used in 21 (51%) patients. Older age (P = .039) and longer TKI therapy (P = .001) were associated with WS. The 2-month landmark analysis found no association of WS development and the rate of molecular relapses. 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.

AB - We aimed to characterize withdrawal syndrome (WS) and evaluate factors associated with its development in the prospective clinical study RU-SKI in patients with chronic myeloid leukemia with deep molecular response who discontinued tyrosine kinase inhibitor (TKI) therapy. In total, 98 adult patients with chronic myeloid leukemia chronic phase, TKI therapy ≥ 3 years, and deep molecular response (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. WS symptoms were found in 41 (42%) of 98 patients with a median time of observation of 25 months (range, 12-42 months). WS grades 1 to 2 and grade 3 were observed in 39 (95%) and in 2 (5%) patients, respectively. The median duration of WS was 5 months (range, 1-25 months). WS was resolved in 37 (90%) patients. Anti-inflammatory therapy was used in 21 (51%) patients. Older age (P = .039) and longer TKI therapy (P = .001) were associated with WS. The 2-month landmark analysis found no association of WS development and the rate of molecular relapses. 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.

KW - Chronic myeloid leukemia

KW - TKI discontinuation

KW - Treatment-free-remission

KW - Tyrosine kinase inhibitors

KW - Withdrawal syndrome

KW - CHRONIC PHASE

KW - TREATMENT-FREE REMISSION

KW - IMATINIB

KW - LONGER

KW - DASATINIB

KW - NILOTINIB

UR - http://www.scopus.com/inward/record.url?scp=85081028331&partnerID=8YFLogxK

UR - https://www.mendeley.com/catalogue/c48169cb-641c-3725-b54a-92af49f07fed/

U2 - 10.1016/j.clml.2019.12.019

DO - 10.1016/j.clml.2019.12.019

M3 - Article

C2 - 32146103

AN - SCOPUS:85081028331

VL - 20

SP - E267-E271

JO - Clinical Lymphoma, Myeloma and Leukemia

JF - Clinical Lymphoma, Myeloma and Leukemia

SN - 2152-2650

IS - 5

ER -