VJHemOnc Podcast

Accelerated-phase MPNs: mutational landscape, challenges, and novel treatment strategies being explored

Aug 10, 2023

Experts discuss the mutational landscape and challenges of treating accelerated-phase myeloproliferative neoplasms (MPNs). They highlight the need for novel treatment strategies, including targeted and combination therapies, to improve outcomes.

08:17

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Episode guests

Anand Patel

Andrew Kuykendall

Jan Philipp Bewersdorf

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Episode notes

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Quick takeaways

Mutational profiles of accelerated and blast phase MPNs are distinct, with enrichment in mutations for ASXL1, TP53, IDH1, and IDH2, suggesting the potential efficacy of targeted agents for these mutations.

Intensive chemotherapy, commonly used in de novo AML, is not as effective in blast phase MPNs, highlighting the need for novel and targeted treatment strategies.

Deep dives

Novel treatment approaches for accelerated phase MPNs

The podcast episode explores novel treatment approaches for MPNs (Myeloproliferative neoplasms) in the accelerated phase. Despite the limited data available, new agents approved for acute myeloid leukemia (AML) show potential for use in accelerated and blast phase MPNs. Treatment approaches such as intensive chemotherapy, HMA-based therapy, and HMA plus vanetoclax-based therapy do not show significant differences in overall survival. Mutational profiles of accelerated and blast phase MPNs are distinct, with enrichment in mutations for ASXL1, TP53, IDH1, and IDH2. Specific targeted agents for ASXL1 are currently unavailable, but early studies suggest the potential efficacy of LSD1 inhibition for ASXL1-mutated MPNs. Similarly, studies are being conducted to investigate drugs specifically for TP53 mutant populations in MDS and AML, such as the CD47 antibody Magrolimab.

Introduction

5min

Challenges in Treating Accelerated-Phase MPNs and the Need for Novel Treatment Strategies

2min

Exploring Novel Treatment Strategies for Accelerated-Phase MPNs

2min

Patients with BCR-ABL negative myeloproliferative neoplasms (MPNs) are at risk of progressing to accelerated-phase or blast-phase disease (MPN-AP/BP). Several mutations, including ASXL1, EZH2, and TP53, are involved in progression to MPN-AP/BP, and there are a number of challenges with treating patients who progress to this stage.

In this podcast, Anand Patel, MD, University of Chicago, Chicago, IL, Andrew Kuykendall, MD, Moffitt Cancer Center, Tampa, FL, and Jan Philipp Bewersdorf, MD, Memorial Sloan Kettering Cancer Center, New York City, NY, discuss the mutational landscape of MPN-AP, and further highlight challenges with treating patients. The experts also comment on novel therapeutic strategies being explored in this space.

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