Median PFS was longer with ponatinib vs imatinib regardless of age, with the greatest difference observed in the subgroup of patients ≥60 years (22.5 months for ponatinib vs 8.3 months for imatinib; hazard ratio: 0.594 [95% CI: 0.332–1.063])….Ponatinib was superior to imatinib in combination with reduced-intensity chemotherapy in the front-line setting for patients with Ph+ ALL, with a clinically significantly higher MRD-neg CR rate at EOI.

On March 19, 2024, the Food and Drug Administration granted accelerated approval to ponatinib (Iclusig, Takeda Pharmaceuticals U.S.A., Inc.) with chemotherapy for adult patients with newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL).

...and BP-CML o] Cytogenetic assessment at screening must demonstrate the BCR-ABL1 fusion by presence of the t(9;22) Philadelphia chromosome....

In patients with Ph+ ALL, the CCyR rates at weeks 0, 12, 24, 52, and 104 were 35.4% (51/144), 77.1% (108/140), 73.6% (53/72), 83.6% (46/55), and 80.0% (36/45), respectively….This two-year post-marketing surveillance of patients with r/i CML and r/r Ph+ ALL has demonstrated the general favorable safety and efficacy of ponatinib to patients in Japan.

Patients were classified by landmark molecular (BCR::ABL1IS ≤0.1% [MMR], ≤1% [MR2], ≤10% [MR1], and >10%) and cytogenetic responses (MCyR, ≤35% Ph+metaphases; CCyR, 0% Ph+ metaphases) at 3, 6, and 12 months. Landmark responses were correlated withprogression-free survival (PFS), overall survival (OS), and molecular response over time (MMR, BCR::ABL1IS≤0.01% [MR4], ≤0.0032% [MR4.5])....In patients with CP-CML in PACE, rapid and deep responses achieved with ponatinib at 3, 6, and 12 months appearto be associated with higher rates of PFS and OS at 4 years.

Ponatinib provided robust responses in the OPTIC trial population comprising patients with heavily pretreated, TKI-resistant CP-CML. In this landmark analysis, attainment of ≤10% BCR::ABL1IS with ponatinib within 12 months was associated with improved long-term PFS outcomes compared with PFS outcomes associated with remaining at >10% BCR::ABL1IS.

This ongoing prospective multi-center registry (NCT03678454) includes ≥18-year-old patients with CML or Ph+ALL eligible for ponatinib treatment per product label.... MMR was achieved in 58% of CML and 52% of Ph+ALL patients. The median time-to-MMR was 170 days in CML and 86 days in Ph+ALL patients. Of the 37 patients who started ponatinib due to intolerance to previous TKIs, 59% (15 CML, 7 Ph+ALL) achieved MMR.... MMR was achieved in 58% of CML and 52% of Ph+ALL patients. The median time-to-MMR was 170 days in CML and 86 days in Ph+ALL patients. Of the 37 patients who started ponatinib due to intolerance to previous TKIs, 59% (15 CML, 7 Ph+ALL) achieved MMR.

A combined 350 PON-treated patients from the PACE and OPTIC trials who have received ≥1 prior 2G TKI were analyzed...The ≤1% BCR-ABL1IS response rates increased over time and ranged from 42% to 52% in the OPTIC IA 45-mg starting dose cohort and in PACE. Progression-free survival and overall survival were 52% and 73%, respectively, in PACE (up to 5 years) and 81% and 93%, respectively, at the OPTIC IA (up to 2 years)...ponatinib shows high response rates and robust survival outcomes in patients who have failed 2G TKIs.

Among patients with CP, AP and BP CML, median age at study entry was 59.1, 33.7 and 48.5 years, respectively; among 37 evaluable patients, 12 (32.4%), 1 (2.7%) and 1 (2.7%) patient(s) had a confirmed BCR-ABL1 mutation. Of evaluable patients, 4 (10.8%) had the T315I mutation. The starting dose of ponatinib for patients with CP CML was 45 mg once daily in 41.5% of patients, 30 mg in 39.6% of patients and 15 mg in 17.0% of patients; 1 (1.9%) patient started ponatinib at another dose....Estimated progression-free survival rates for patients with CP CML at Months 12 and 24 were 86.6% (95% CI, 77.8-96.4%) and 83.7% (95% CI, 73.8-94.9%), respectively. Corresponding overall survival rates were 96.2% (95% CI, 91.1-100.0%) and 93.1% (95% CI, 85.6-100.0%), respectively....Data show that ponatinib has a favorable efficacy and safety profile in patients with CML treated in standard clinical practice in Italy. By Month 6, most patients had achieved CCyR and 44% of patients achieved MMR in 2/3L.

Among patients with accelerated-phase CML, 55% (95% CI, 44 to 66) had a major hematologic response by 6 months (the primary end point). A major cytogenetic response was seen in 39%, 24% had a complete cytogenetic response, and 16% had a major molecular response....High response rates were observed among patients with BCR-ABL mutations, including those with the T315I mutation, and among those without BCR-ABL mutations...ponatinib showed clinically significant activity in patients with CML and those with Ph-positive ALL.