Patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) who relapsed after frontline ponatinib-based therapies had a high response rate to salvage treatments, including immunotherapies and TKIs, with 90% achieving second remission, according to a recent correspondence in the American Journal of Hematology.
Patients with central nervous system (CNS)-only relapses had better survival outcomes compared with those with bone marrow relapses.
Ponatinib, a tyrosine kinase inhibitor (TKI), is especially effective against T315I mutations, which are a primary cause of relapse with earlier-generation TKIs. While ponatinib-based therapies have yielded promising results some patients still experience relapse, and the mechanisms driving resistance remain unclear, according to the researchers.
The study retrospectively analyzed 22 patients who relapsed following frontline ponatinib-based treatment. These relapses were categorized as either ponatinib-resistant (those who relapsed while on ponatinib) or ponatinib-intolerant (relapse after discontinuation due to toxicity). Bone marrow relapse was most common, though CNS-only relapses also occurred, particularly among patients who received chemotherapy-free regimens. Notably, patients with CNS relapses had better overall survival (86% at two years) compared with those with bone marrow relapses (31% at two years).
Salvage therapies were effective for 90% of patients, with many achieving second remission, often with the use of immunotherapy-based treatments, such as blinatumomab, inotuzumab ozogamicin, or chimeric antigen receptor (CAR) T-cell therapy. Among patients who responded to salvage therapy, some went on to receive allogeneic hematopoietic stem cell transplantation (HSCT) in second remission. However, long-term remission was observed even in some patients who did not undergo HSCT, indicating that certain immunotherapies may offer a durable solution.
Reference
Short NJ, Jabbour E, Nasr LF, et al. Characteristics and outcomes of patients with relapsed Philadelphia chromosome-positive acute lymphoblastic leukemia after failure of a frontline ponatinib-containing therapy. Am J Hematol. 2024;99(7):1423-1426. doi:10.1002/ajh.27329
