TY - JOUR
T1 - The outcomes of patients with chronic myeloid leukemia treated with third-line BCR::ABL1 tyrosine kinase inhibitors
AU - Jabbour, Elias J.
AU - Sasaki, Koji
AU - Haddad, Fadi G.
AU - Issa, Ghayas C.
AU - Garcia-Manero, Guillermo
AU - Kadia, Tapan M.
AU - Jain, Nitin
AU - Yilmaz, Musa
AU - DiNardo, Courtney D.
AU - Patel, Keyur P.
AU - Kanagal-Shamanna, Rashmi
AU - Champlin, Richard
AU - Khouri, Issa F.
AU - Dellasala, Sara
AU - Pierce, Sherry A.
AU - Kantarjian, Hagop
N1 - Publisher Copyright:
© 2023 Wiley Periodicals LLC.
PY - 2023/4
Y1 - 2023/4
N2 - The BCR::ABL1 tyrosine kinase inhibitors (TKIs) have improved the outcomes of patients with chronic myeloid leukemia (CML). After failing second-generation TKI (2G-TKI), the optimal third-line therapy in chronic phase CML (CML-CP) is not well established. We analyzed 354 patients with CML-CP treated with a third-line BCR::ABL1 TKI at our institution, and in the PACE and OPTIC trials, and evaluated the outcome after alternate 2G-TKIs or ponatinib. We performed a propensity score matching analysis to compare outcomes and multivariate analysis to identify variables associated with survival. One hundred seventy-three (49%) patients received 2G-TKIs and 181 (51%) ponatinib. Patients in the ponatinib group had more cardiovascular risk factors (34% versus 19%) and higher disease burden (BCR::ABL1 transcript levels >1%, 165/175 [94%] versus 75/135 [55%]; p <.001) compared with the 2G-TKI group. Among the 173 evaluable patients treated with ponatinib, 89 (52%) achieved 2 + −log reduction of baseline transcripts (20% 2-log reduction and 32% 3 + −log reduction). Among the 128 evaluable patients treated with 2G-TKIs, 44 (34%) achieved 2 + −log reduction of baseline transcripts (13% 2-log reduction and 21% 3 + −log reduction). With a median follow-up of 46 months, the 3-year progression-free survival was 59% (60% before matching) with 2G-TKI and 83% (81% before matching) with ponatinib (p <.001). The 3-year survival was 83% (81% before matching) with 2G-TKI and 87% (89% before matching) with ponatinib (p =.03). By multivariate analysis, third-line therapy with ponatinib was the only independent factor associated with better survival (p =.003). In conclusion, ponatinib is an optimal treatment for patients with CML-CP failing two prior TKIs.
AB - The BCR::ABL1 tyrosine kinase inhibitors (TKIs) have improved the outcomes of patients with chronic myeloid leukemia (CML). After failing second-generation TKI (2G-TKI), the optimal third-line therapy in chronic phase CML (CML-CP) is not well established. We analyzed 354 patients with CML-CP treated with a third-line BCR::ABL1 TKI at our institution, and in the PACE and OPTIC trials, and evaluated the outcome after alternate 2G-TKIs or ponatinib. We performed a propensity score matching analysis to compare outcomes and multivariate analysis to identify variables associated with survival. One hundred seventy-three (49%) patients received 2G-TKIs and 181 (51%) ponatinib. Patients in the ponatinib group had more cardiovascular risk factors (34% versus 19%) and higher disease burden (BCR::ABL1 transcript levels >1%, 165/175 [94%] versus 75/135 [55%]; p <.001) compared with the 2G-TKI group. Among the 173 evaluable patients treated with ponatinib, 89 (52%) achieved 2 + −log reduction of baseline transcripts (20% 2-log reduction and 32% 3 + −log reduction). Among the 128 evaluable patients treated with 2G-TKIs, 44 (34%) achieved 2 + −log reduction of baseline transcripts (13% 2-log reduction and 21% 3 + −log reduction). With a median follow-up of 46 months, the 3-year progression-free survival was 59% (60% before matching) with 2G-TKI and 83% (81% before matching) with ponatinib (p <.001). The 3-year survival was 83% (81% before matching) with 2G-TKI and 87% (89% before matching) with ponatinib (p =.03). By multivariate analysis, third-line therapy with ponatinib was the only independent factor associated with better survival (p =.003). In conclusion, ponatinib is an optimal treatment for patients with CML-CP failing two prior TKIs.
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U2 - 10.1002/ajh.26852
DO - 10.1002/ajh.26852
M3 - Article
C2 - 36683287
AN - SCOPUS:85147352988
SN - 0361-8609
VL - 98
SP - 658
EP - 665
JO - American journal of hematology
JF - American journal of hematology
IS - 4
ER -