KEY TAKEAWAYS
- This phase II trial hypothesized that Ponatinib + DAC + VEN may lead to high response rates and facilitate SCT.
- The study enrolled patients aged 18+ with CML-AP, CML-MBP or Ph+AML with ECOG PS ≤ 3 to receive DAC+VEN+ponatinib for 24 cycles.
- The study showed promising results in pts with advanced Ph+ leukemias.
Chronic myeloid leukemia (CML) in accelerated phase (AP) /myeloid blast phase (MBP) or Philadelphia-chromosome positive (Ph+) is difficult to treat. Researchers hypothesized that combining Ponatinib, DAC, and VEN may lead to high response rates and facilitate allogeneic stem cell transplantation (SCT).
The study enrolled patients(pts) with CML-AP, CML-MBP, or Ph+ AML to receive DAC + VEN + ponatinib. The therapy of DAC (20 mg/m2/day) x 5 days, VEN (400 mg equivalent dose/day) x 21 days, and ponatinib (45mg/day) x 21 days in cycle 1 and then continuously in cycles 2-24 was well-tolerated, and the overall response rate (ORR) was 75%. Ponatinib was reduced for pts in CR/CRi and CMR. Intrathecal prophylaxis with cytarabine was recommended.
Out of 15 pts 4 were treated for CML-AP, 10 for CML-MBP, and 1 for Ph+ AML.
Of these, 73% had prior exposure to TKIs, including 4 with prior ponatinib. Among the 13 tested pts, 38% had ABL1 kinase domain mutations (T315I, Q252H, L384M in 1 patient each and E255K in 2 pts). Pts received a median of 3 cycles (range, 1-7). A total of 73% responded, including 6 with CR/CRi and 5 with MLFS. The best response was observed after cycle 1 in 82% of responders. All 4 CML-AP pts responded, and 9 of 11 pts (82%) with prior TKI exposure responded. Subsequent SCT was undergone by 4 pts. At a median follow-up of 9.8 months, the median overall survival (OS) was 11.0 months, with an estimated 10-month OS of 63%. The median relapse-free survival was 5.7 months. Among 11 responders, 5 relapsed (one after SCT), 6 have ongoing response (3 after SCT). One patient experienced grade 3 mucositis. No grade 4-5 non-hematological adverse events were observed. Of 10 patients who received more than one cycle, 5 had cycle delays of more than one week due to cytopenias. There was 0% 60-day mortality, with two deaths in the study(leukemia, infection in MLFS).
The study showed promise in poor-risk pts with Ph+ leukemias.
Source: https://ascopubs.org/doi/abs/10.1200/JCO.2023.41.16_suppl.e19044
Clinical Trial: https://classic.clinicaltrials.gov/ct2/show/NCT04188405
Jayastu Senapati, Farhad Ravandi, Courtney Denton Dinardo, Ghayas C. Issa, Koji Sasaki, Marina Konopleva, Walid Macaron, Lewis Fady Nasr, Marianne Zoghbi, Cedric Christophe Nasnas, Naveen Pemmaraju, Kelly Sharon Chien, Maro Ohanian, Elias Jabbour, Abhishek Maiti, Hagop M. Kantarjian, and Nicholas James Short. Journal of Clinical Oncology (2023) 41:16_suppl, e19044-e19044.
