Early response may predict outcomes in heavily pretreated chronic myeloid leukemia
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Early response to ponatinib appeared predictive of survival among certain patients with chronic myeloid leukemia, according to findings presented at Society of Hematologic Oncology Annual Meeting.
The phase 2 PACE trial included heavily pretreated patients with chronic-phase CML.
Study participants who achieved cytogenic or molecular response to ponatinib (Iclusig, Takeda) at 3 months or 6 months achieved longer PFS and OS, 5-year data showed.
Sequential tyrosine kinase inhibitor therapy and presence of BCR::ABL1 mutations are associated with poor outcomes in chronic-phase CML.
Ponatinib is a third-generation TKI designed to inhibit BCR::ABL1.
Prior studies showed early landmark response to BCR::ABL1 TKI therapy has been linked to better long-term outcomes among patients with newly diagnosed chronic-phase CML; however, whether this is true for patients who had been treated with multiple prior TKIs had not been established.
The single-arm, open-label, multicenter PACE trial assessed the efficacy of ponatinib for 267 adults with chronic-phase CML and ECOG performance status of 0 to 2. The analysis included 203 patients who were intolerant of or resistant to nilotinib (Tasigna, Novartis) or dasatinib (Sprycel, Bristol Myers Squibb), and 64 patients who had T3151 mutations.
Participants received ponatinib at a starting dose of 45 mg once daily. A protocol amendment reduced the dose to 15 mg once daily for patients who achieved major cytogenetic response and 30 mg daily for those who did not.
Major cytogenetic response by 12 months served as the primary endpoint.
Hagop Kantarjian, MD, professor and chair of the department of leukemia at The University of Texas MD Anderson Cancer Center, and colleagues performed a post-hoc analysis to determine if landmark cytogenetic or molecular responses at 3 months, 6 months and 12 months correlated with long-term efficacy outcomes.
Median follow-up was 56.8 months.
Researchers reported significantly better outcomes among patients who achieved major cytogenetic response (4-year PFS, 71% vs. 37%; P < .0001; 4-year OS, 87% vs. 69%; P = .0006) or complete cytogenetic response (4-year PFS, 68% vs. 47%; P = .0004; 4-year OS, 87% vs. 73%; P = .0017) at 3 months than those who did not.
Results also showed better outcomes among patients who achieved major cytogenetic response (4-year PFS, 64% vs. 43%; P < .0001; 4-year OS, 85% vs. 78%; P = .0208) or complete cytogenetic response (4-year PFS, 72% vs. 41%; P < .0001; 4-year OS, 87% vs. 79%; P = .0088) at 6 months than those who did not.
Patients who achieved major molecular response at 3 months achieved better 4-year PFS (80% vs. 54%; P = .001) and numerically higher 4-year OS (89% vs. 80%) than those who did not.
Patients who achieved major molecular response at 6 months achieved better 4-year PFS (83% vs. 53%; P < .0001) and 4-year OS (93% vs. 82%; P = .0067) than those who did not.
Patients who achieved major molecular response at 3 months tended to be younger, more recently diagnosed and more likely to have a mutation detected at study entry.
“In this heavily pretreated [chronic-phase] CML population, achieving cytogenetic and molecular responses at 3 and 6 months was associated with improved long-term PFS and OS,” Kantarjian and colleagues wrote. “These results underscore the potential utility of assessing cytogenetic and molecular responses at early time points, as they are strong predictors of favorable long-term outcomes.”
In addition, patients who did not achieve response at 3 months still may achieve response later and experience favorable long-term outcomes, suggesting therapy can be continued if it is well-tolerated, Kantarjian and colleagues wrote.
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Kantarjian H, et al. Abstract CML-310. Presented at: Society of Hematologic Oncology Annual Meeting; Sept. 6-9, 2023; Houston.
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