Combining ponatinib with reduced-intensity chemotherapy elicited a high rate of minimal residual disease (MRD)-negative complete remissions and no new safety signals in patients with Philadelphia chromosome–positive acute lymphoblastic leukemia.
Ponatinib (Iclusig), when combined with reduced-intensity chemotherapy, bested imatinib (Gleevec) in yielding higher rates minimal residual disease (MRD)-negative complete remission (CR) in patients with newly diagnosed Philadelphia Chromosome (Ph)-positive acute lymphoblastic leukemia (ALL), effectively meeting the primary end point of the phase 3 PhALLCON trial (NCT03589326).1
No new safety signals with the combination were observed, according to the press release issued by Takeda.
“Ph-positive ALL is a fast-progressing disease with no targeted treatments currently approved in the frontline for patients in the United States. There is an urgent need for an effective treatment that can suppress the development of difficult-to-treat mutations, which are associated with poor long-term outcomes,” Awny Farajallah, MD, head of Global Medical Affairs Oncology at Takeda, stated in the press release. “We are excited to see how [ponatinib] may be able to address this gap in care for these patients and look forward to sharing the results.”
The open-label, parallel-assignment, randomized trial enrolled patients with newly diagnosed Ph-positive or BCR-ABL1–positive ALL who were at least 18 years of age and who had an ECOG performance status of 0 to 2.2,3
Exclusion criteria include having a history or current diagnosis of chronic phase, accelerated phase, or blast phase chronic myeloid leukemia; prior or current treatment with any systemic anticancer therapy and/or radiotherapy for ALL; uncontrolled active serious infection that could interfere with treatment; major surgery within 28 days prior to randomization; and a history of acute pancreatitis within 1 year of screening; among others.
Study participants were randomly assigned 2:1 to receive ponatinib at a daily dose of 30 mg or imatinib at a daily dose of 600 mg paired with reduced-intensity chemotherapy in induction phase (cycles 1 to 3), consolidation phase (cycles 4 to 9), and maintenance phase (cycles 10 to 20). At the end of the 20 cycles, participants will remain on either TKI.
Treatment will continue until relapse from CR, disease progression, intolerable toxicity, withdrawn consent, patients proceed to hematopoietic stem cell transplant, the study is completed, death, or the study is terminated by the sponsor.
The primary end point of the trial is MRD-negative CR at the end of the indication phase of treatment, which was approximately 3 months. Secondary end points include event-free survival, CR/incomplete blood count recovery rates, molecular response rates, MRD-negative CR duration, primary induction failure, overall response rate, CR duration, time to treatment failure, overall survival, and safety.
In January 2019, the first patient underwent randomization. Approximately 226 patients were randomized as of February 2022.
Additional findings from the trial will be shared with regulatory authorities and with the scientific community in the future.