Is the 2^nd Generation Tyrosine Kinase-Inhibitor a Better Initial Therapy Than Imatinib in Persons with Chronic Myeloid Leukemia Presenting in Accelerated Phase: A Multicenter Retrospective Study

Objectives Compare the treatment responses and outcomes between persons with chronic myeloid leukemia (CML) presenting in accelerated phase receiving a 2^nd-generation tyrosine kinase inhibitor (2G-TKI) and imatinib as initial therapy.

Methods Data from 442 consecutive subjects with CML presenting in accelerated phase according to the European LeukemiaNet (ELN) 2020 criteria from 32 centers were retrospectively collected. Propensity score matching (PSM) was performed to adjust for differences in baseline co-variates between subjects receiving a 2G-TKI or imatinib as initial therapy. Cumulative incidences of CCyR, MMR and MR^4.5 were calculated using the Fine-Gray model. Transformation was defined as blood or bone marrow blasts ≥ 30% during TKI-therapy. Transformation-free survival (TFS) and survival were calculated by the Kaplan-Meier model.

Results 442 subjects with CML presenting in accelerated phase were reviewed, including 147 (33%) received 2G-TKI and 295 (67%) received imatinib as initial therapy. 270 (61%) were male, median age was 43 years (Interquartile range [IQR], 31-55 years), median follow-up was 28 months (IQR, 13 - 53 months) in the 2G-TKI cohort and 51 months (IQR, 25 - 94 months) in the imatinib cohort reflecting the later availability of 2G-TKIs (p < 0.001), median treatment duration was 19 months (IQR, 9 - 41 months) in the 2G-TKI cohort and 32 months (IQR, 12 - 68 months) in the imatinib cohort (p < 0.001). 28 (26%) receiving 2G-TKI and 100 (34%) subjects receiving imatinib switched to another TKI during treatment. 379 subjects were identified by a 2:1 propensity-score matching in the 2G-TKI (n = 139; 37%) and imatinib (n = 240; 63%) cohorts.

In the 2G-TKI and imatinib cohorts, the cumulative incidence of 2-year CCyR was 87% (95% Confidential Interval [CI], 86%, 87%) vs. 84% (84%, 84%, p < 0.001); MMR, 83% (82%, 83%) vs. 65% (65%, 65%, p < 0.001); MR^4.5, 43% (42%, 44%) vs. 29% (28%, 29%, p = 0.006) when switching to another TKI, a transplantation and death were considered as competing events. When switching to another TKI was not considered as a competing event, cumulative incidences of 2-year CCyR were 91% (91%, 92%) vs. 83% (83%, 83%, p < 0.001); MMR, 80% (80%, 81%) vs. 66% (66%, 66%, p = 0.002); MR^4.5, 40% (40%, 41%) vs. 28% (27%, 28%, p = 0.005) in the 2G-TKI and imatinib cohorts.

The 2-year probabilities of TFS were 88% (81%, 94%) vs. 92% (88%, 96%, p = 0.116); survival, 97% (94%, 100%) vs. 98% (96%, 100%, p = 0.530) in the 2G-TKI and imatinib cohorts when censored at switching to another TKI, a transplantation or at last follow-up. Similarly, 2-year probabilities of TFS were 94% (89%, 98%) vs. 93% (90%, 96%, p = 0.868); survival, 97% (94%, 100%) vs. 96% (93%, 98%, p = 0.562) in the 2G-TKI and imatinib cohorts when censored at a transplantation or at last follow-up.

Conclusions Persons with CML presenting in accelerated phase receiving a 2G-TKI as initial therapy achieved higher cumulative incidences of MMR and MR^4.5 than those receiving imatinib, but similar TFS and survival.

No relevant conflicts of interest to declare.