Blood Podcast – "How I Treat Myeloproliferative Neoplasms"

Podcast: Blood Podcast
Host: American Society of Hematology
Date: April 17, 2025
Guests: Dr. Claire Harrison, Dr. Aaron Gerds, Prof. Andreas Reiter
Moderator: Dr. Jason Gottlieb (Associate Editor, Blood)

Episode Overview

This episode introduces the new "How I Treat" series on myeloproliferative neoplasms (MPNs) featured in Blood. Dr. Jason Gottlieb hosts contributing expert authors Dr. Claire Harrison, Dr. Aaron Gerds, and Prof. Andreas Reiter to discuss recent advances in understanding, diagnosing, and treating MPNs, with a focus on:

• Evolving risk stratification and management of polycythemia vera (PV), especially "low risk" patients,
• Modern approaches to anemia in myelofibrosis, and
• Cutting-edge diagnostics and therapy for myeloid/lymphoid neoplasms with tyrosine kinase gene fusions.

Key Discussion Points and Insights

Introduction to the How I Treat Series

• The series features six in-depth review articles on major MPN challenges, authored by global experts.
• It highlights a shift towards personalized, data-driven care, bench-to-bedside collaborations, and shared decision-making.
  • [00:25] Jason Gottlieb: “The clinical and molecular heterogeneity of MPNs… leads to a melding of data-driven algorithms with personalized care approaches that are informed by shared decision making.”

1. Rethinking “Low Risk” in Polycythemia Vera (PV)

Speaker: Dr. Claire Harrison

• Classic stratification (age, thrombosis history) is outdated.
• Modern risk assessment must integrate:
  • Cardiovascular risk factors
  • Degree of leukocytosis
  • JAK2 allele burden (>50%)
  • Splenomegaly
  • Platelet count
• Notable quote:
  • [02:43] Claire Harrison: “Low risk PV is not no risk. These patients have a lifetime risk of thrombosis… [and] disease transformation.”
• New, better-tolerated treatments (pegylated interferon, ruxolitinib) have changed practice.
• Rational for cytoreduction in low-risk PV is expanding:
  • Safer, more tolerable drugs
  • Potential to impact clone size, molecular responses, and long-term outcomes
  • [12:20] Harrison: “We realise that impacting the clone size… may impact the longer term outcome for disease.”

Data, Laboratory, and Personalization

• Ongoing need to integrate real-world data and advanced analytics (machine learning) to better stratify and individualize PV care.
  • [31:16] Harrison: “I’m excited about our ability to collate real world data and do these kind of machine learning… technologies.”

2. Anemia in Myelofibrosis: Complex Etiology & Emerging Therapies

Speaker: Dr. Aaron Gerds

• Causes are multifactorial:
  • Dyserythropoiesis (bone marrow mutations),
  • Inflammatory block (via hepcidin),
  • JAK inhibitor-induced suppression,
  • Hemolysis or sequestration.
  • [04:39] Gerds: “…one of the key principles of treating myelofibrosis is raising hemoglobin… the tricky part about anemia in myelofibrosis, it’s generally multifactorial.”

JAK Inhibitors & Anemia

• There are four FDA-approved JAK inhibitors (ruxolitinib, fedratinib, momelotinib, pacritinib), each with distinct anemia profiles.
• Even “anemia supportive” JAK inhibitors can cause anemia.
• Agents like momelotinib and pacritinib inhibit ACVR1, potentially alleviating anemia for some patients, but responses are varied due to multifactorial disease.
  • [20:12] Gerds: “All the JAK inhibitors can lead to anemia… even the ones that are supposed to be anemia supportive can in fact themselves cause anemia.”
• Clinical approach individualized:
  • Maintain quality of life if spleen/symptom control is good—add supportive agents (ESAs, luspatercept, danazol) as needed.
  • Consider switching JAKi or dose-modifying in more complex cases.
  • [24:07] Gerds: “We aren’t beholden to a single JAK inhibitor anymore, and we have that flexibility in the care plan.”

Forward-Looking Therapeutics

• New anemia drugs targeting ACVR1 more precisely and agents like luspatercept are in clinical trials.
• The ultimate horizon: therapies that induce durable, deep responses—potentially eliminating need for supportive care or transplant:
  • [32:50] Gerds: “Therapies that clean out disease…that, dare I say, will put transplanters out of business someday. That’s really what we’re getting at…”

3. Myeloid/Lymphoid Neoplasms with Tyrosine Kinase Fusions

Speaker: Prof. Andreas Reiter

• Diagnosis is complex:
  • Eosinophilia (almost universal in FIP1L1-PDGFRA),
  • Frequent finding of monocytosis,
  • Use of serum tryptase, vitamin B12,
  • Bone marrow phenotype (MPN +/- MDS, mastocytosis, fibrosis).
  • Extramedullary disease (e.g. lymphoma, myelosarcoma) is a hallmark.
  • [06:12] Reiter: “…eosinophilia is present, for example, in FIB1, L1PDGFRA in almost every patient… the higher the eosinophils, you may also find monocytosis.”
• Advanced molecular diagnostics needed:
  • Many fusions (esp. FIP1L1-PDGFRA) are cytogenetically cryptic—require FISH or RT-PCR, sometimes even whole genome sequencing.
  • Always confirm suspect fusions by RT-PCR; some fusions are not functional drivers.
  • [08:17] Reiter: “You have to do cytogenetics… fish… pcr. It has really become very complex and you really need a very good lab to do all these various technologies.”

Prognostic Implications / Therapeutic Approach

• Favorable fusions (PDGFRA/PDGFRB):
  • Excellent, durable, and often molecular remissions with imatinib alone, even possible treatment-free remissions after years.
  • [26:01] Reiter: “…patients with PDGFR alpha and PDGFR beta fusion genes, they show excellent responses to imatinib… you can test 100mg… achieve rapid and durable complete hematologic and... molecular remission.”
• Unfavorable fusions (FGFR1, others):
  • Present as acute leukemia or extramedullary disease—often require intensive chemo, TKIs as maintenance, and (if eligible) allogeneic transplant.
  • [26:01] Reiter: “Most of these patients either already present in something like blast face acute leukemia… you first have to consider intensive chemotherapy…”

Diagnostic Frontiers and Challenges

• Ongoing discovery of cryptic kinase fusions—phenotypes may show basophilia, monocytosis, or even (mastocytosis-like) features without eosinophilia.
• Need for awareness of rare, atypical presentations; continued development in better diagnostic and targeted therapeutic strategies.
  • [34:26] Reiter: “Really, the most important scientific issue is that I’m sure there are patients out there with a fusion chain which has not yet been identified.”

Notable Quotes & Memorable Moments

• [03:27] Claire Harrison, on PV risk:
  “Low risk PV is not no risk… lifetime risk of thrombosis is significantly higher than the general population...”
• [20:12] Aaron Gerds, on JAK inhibitors:
  “All the JAK inhibitors can lead to anemia… so just because it’s an anemia supportive JAK inhibitor doesn’t mean it can’t cause anemia.”
• [26:01] Andreas Reiter, on imatinib response:
  “Patients achieve rapid and durable complete hematologic and also molecular remission... after two, three years in complete molecular remission, we dare to stop the drug.”
• [14:35] Claire Harrison, on JAK2 VAF:
  “I frame it as it’s of interest. We’re not totally sure how to use that... maybe as important is that you do stop smoking, you do lose weight, we do address your cardiovascular risk...”
• [32:50] Aaron Gerds, on future therapies:
  “Therapies that clean out disease...that, dare I say, will put transplanters out of business someday.”

Timestamps for Key Segments

• [00:25] Intro & series scope: Dr. Gottlieb introduces guests and review topics
• [02:43] Dr. Harrison: modern PV risk stratification, rationale for cytoreduction in “low-risk” patients
• [04:39] Dr. Gerds: multifactorial causes of anemia in MF
• [06:12] Prof. Reiter: diagnostic clues for myeloid/lymphoid neoplasms with tyrosine kinase fusions
• [08:17] Prof. Reiter: advanced diagnostic tools and limitations
• [12:20] Dr. Harrison: how new therapies are shifting PV management
• [14:35] Discussion: patient concerns with JAK2 mutation burden, clinical approach
• [20:12] Dr. Gerds: JAK inhibitors, anemia, clinical decision tools
• [23:22] Dr. Gerds: strategies for managing emergent anemia on JAK inhibitors; using ESAs, danazol, or switching agents
• [26:01] Prof. Reiter: prognosis, therapy, and transplantation in tyrosine kinase fusion neoplasms
• [31:16] Dr. Harrison: research priorities for PV, real-world data, machine learning
• [32:50] Dr. Gerds: future therapies for MF anemia, depth of response
• [34:26] Prof. Reiter: unmet needs—diagnostic frontiers, resistance, need for new drugs
• [37:59] Moderator concludes, thanks guests

Conclusion

This episode illustrates both the complexity and ongoing evolution of the MPN field. Experts discuss how shifts in risk assessment, broader diagnostic tools, and a growing therapeutic armamentarium enable more sophisticated, patient-centered management. Major themes include the drive towards personalized care, integration of new evidence into real-world practice, and the promise of emerging therapies to alter disease course fundamentally.

For more detail, consult the full “How I Treat” review series at bloodjournal.org.

(End of summary)