Outcomes for patients with myeloproliferative neoplasm blast phase (MPN-AP/BP) remain poor despite the introduction of new therapies, according to a retrospective, multicenter cohort study published in Blood Advances. The study, which investigated outcomes among 202 patients diagnosed and treated in the current era of myeloid therapies, found a median overall survival (OS) of just 0.86 years, highlighting the urgent need for more effective treatment strategies.
Key Findings on Treatment Outcomes
The research revealed no significant differences in survival based on first-line treatment type. Common frontline strategies included intensive chemotherapy, DNA methyltransferase inhibitor (DNMTi)-based regimens, and DNMTi plus venetoclax-based regimens. These findings suggest that current treatment approaches, including newer venetoclax combinations, have not significantly improved outcomes in this challenging patient population.
The Role of Stem Cell Transplant
Allogeneic hematopoietic stem cell transplant (allo-HSCT) continues to play a crucial role in the management of MPN-AP/BP. An analysis of 65 patients who underwent allo-HSCT showed a median OS of 2.30 years from the time of transplant, reinforcing the importance of considering transplant for eligible patients.
Expert Perspectives
According to Evan Chen, MD, a medical oncologist at Dana-Farber Cancer Institute, the study's findings underscore two critical points: "First, outcomes of patients with MPN-AP/BP remain poor despite intensive chemotherapy and more recently developed, less-intensive venetoclax-based combinations. Second, a bone marrow transplant remains necessary for the possibility of long-term survival in the current treatment era for these patients."
Ruben A. Mesa, MD, president and executive director of Atrium Health Wake Forest Baptist Comprehensive Cancer Center, noted that only 14% of patients were enrolled in clinical trials, emphasizing the need for increased participation in research to advance treatment options.
Andrew Srisuwananukorn, MD, assistant professor in the division of hematology at The Ohio State University Comprehensive Cancer Center, stated that the study "revealed that there is no single treatment strategy that is superior for these patients, and therefore clinicians should continue to rely on shared decision making for personalized treatment plans for patients with MPN who progress to accelerated or blast phase." He also emphasized the importance of prompt referral for allo-HSCT eligibility.
Ongoing Research and Future Directions
Experts agree on the necessity for additional research to elucidate the biology of MPN-AP/BP and identify biomarkers that can inform treatment decisions. The genetic landscape, enriched with high-risk mutations such as ASXL1, EZH2, SRSF2, and IDH1/2, requires further investigation. Notably, TP53 mutations are enriched in more than 20% of the population and are independently associated with worse OS.
The Myeloproliferative Neoplasm Research Consortium (MPN-RC) is currently investigating the combination of JAK/IDH inhibition in MPN-AP/BP in a clinical trial of patients with identified IDH2 mutations (NCT04281498).
Dr. Chen and colleagues are also conducting a phase 1 study of venetoclax, navitoclax, and decitabine for advanced myeloid malignancies, including MPN-AP/BP (NCT05455294). Preliminary results are expected to be shared at the 2024 ASH Annual Meeting. "The novelty of this triplet regimen is in leveraging BCL-XL inhibition by navitoclax on top of a conventional venetoclax/HMA backbone," Dr. Chen explained.
Other promising biological targets under preclinical investigation include bromodomain inhibitors, hypoxia-inducible factor, dual specificity phosphatase 6, and lysine specific demethylase 1 inhibition.
Ultimately, collaborative efforts between researchers, clinicians, and pharmaceutical companies are essential to develop more effective treatments and improve outcomes for patients with MPN-AP/BP.
