Use of a 2-step dose reduction of tyrosine kinase inhibitors (TKI) before treatment-free remission was a promising approach for discontinuation of TKIs in patients with chronic myeloid leukemia (CML), according to data presented at the EHA 2022 Hybrid Congress.
“Many CML patients had drug-dependent adverse events [AEs] during long-term TKI treatment,” explained Margarita Gurianova, MD, of the National Research Centre for Hematology, Moscow, and colleagues in an e-poster. “TKI dose reduction may be safely used for AE correction or prevention in patients with optimal response.”
Dr Gurianova and colleagues presented first interim results of a prospective study of dose reduction and discontinuation in 103 patients with CML.
The trial used a 2-phase strategy. Phase 1 was a TKI dose reduction phase lasting at least 12 months. Phase 2 was a treatment-free remission phase lasting at least 24 months. TKI dose reduction consisted of 2 steps each lasting 6 months. Inclusion into the treatment-free remission phase was done after dose reduction in patients with a deep molecular response (DMR) duration of 2 years or longer and a molecular response of at least 4.5 at the time of TKI stop.
The median TKI duration was 7 years, and the median duration of major molecular response (MMR) and DMR was 3.3 years and 2.5 years, respectively. At study initiation, 67% of patients were receiving imatinib and 33% were receiving a second-generation TKI.
Sixty-four patients completed the first dose reduction step lasting for 6 months, and there was no MMR loss after this reduction. Four patients lost DMR on imatinib at 300 mg, but 3 were restored to DMR in 3 months at the same dose thereafter.
Fifty-seven patients completed the second dose reduction phase. Two patients lost MMR on imatinib at 200 mg. Nine patients lost DMR: 6 on imatinib at 200 mg, 1 on dasatinib at 25 mg, and 2 on nilotinib at 200 mg.
Forty-nine patients were included in the treatment-free remission phase of the study. Approximately one-third of these patients had a history of at least 1 TKI discontinuation.
Survival without MMR loss was 61% in patients on their first TKI stop and 41% in patients on their second TKI stop. Survival without MMR loss was 54% after 12 months in the total group.
TKI therapy was resumed at reduced doses after loss of MMR. The likelihood of MMR recovery was 86%, and the likelihood of DMR recovery was 83% after 6-month resumption of TKIs at reduced doses.
“The probability of recovery of MMR and DMR allows us to consider the possibility of an approach to TKI therapy at reduced doses in CML patients after molecular relapse in TFR,” the researchers concluded.
Disclosures are not available for this presentation.
Gurianova M, Shukhov O, Chelysheva E, et al. First interim results of the prospective study of dose reduction and discontinuation of tyrosine kinase inhibitors (READIT-2020) in chronic myeloid leukemia patients with deep molecular response. Presented at EHA 2022; June 9-12, 2022. Abstract P702.