SRSF2 Mutation in JAK2V617F-Associated MPNs Reduces Polycythemia, Impairs Hematopoietic Progenitor Activity

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Ryner Lai

SFSR2 mutation reduces polycythemia and impairs the activity of hematopoietic stem/progenitor cells in JAK2V617F-associated myeloproliferative neoplasms (MPNs), according to a study published in Blood Cancer Journal. 

Prior research has shown that JAK2V617F is one of the most common somatic mutations associated with MPNs; in turn, SFSR2 mutations are commonly associated with JAK2V617F, especially in myelofibrosis. Nevertheless, the consequences of SRSF2 mutation in JAK2V617F-associated MPNs have yet to be clearly elucidated in existing medical literature.

Researchers conducted a study on Cre-induced SRSF2P95H/+JAK2V617F/+ knock-in mice. The research team induced Mx1Cre expression by injecting mice models with 3 doses of polyinosine-polycytosine (pl-pC) at a dose of 300 μg at 4 weeks after birth. This allowed the researchers to identify the impact of SRSF2 mutation on blood parameters and the bone marrow 24 weeks after pl-pC administration (or 28 weeks after birth).

Additional mutations or genetic abnormalities are required in association with SRSF2P95H and JAK2V617F mutations in the development of full-blown myelofibrosis.

The research team discovered that concurrent SRSF2P95H and JAK2V617F mutations resulted in a reduction in the polycythemia phenotype; mice with concurrent mutations demonstrated a significant reduction in erythrocytes, leukocytes, platelets, neutrophils, and hematocrit parameters compared to mice that only had the JAK2V617F mutation. In addition, mice with concurrent SRSF2P95H and JAK2V617F mutations had higher mean corpuscular volume (MCV) volumes compared to JAK2V617F/+ mice.

Although Jak2V617F/+ mice demonstrated significant splenomegaly, the investigators found that SRSF2P95H/+JAK2V617F/+ mice exhibited reduced spleen size. In addition, whereas JAK2V617F/+ mice exhibited bone marrow hypercellularity alongside significant increases in erythroid precursors and megakaryocyte clusters, SRSF2P95H/+JAK2V617F/+ mice exhibited normal bone marrow cellularity.

The research team found absent/mild bone marrow fibrosis at 24 weeks in both mice groups. They also reported that SRSF2P95H mutation reduced the competitiveness of hematopoietic stem/progenitor cells; in addition, mice with this mutation had reduced transforming growth factor (TGF)-β levels and increased expressions of S100A8 and S100A9 compared to mice without this mutation; overexpression of S100A8 and S100A9 in turn led to erythroid differentiation defects and myelodysplastic syndrome pathogenesis.

“In conclusion, we demonstrate that SRSF2P95H mutant reduces development of bone marrow fibrosis in JAK2V617F-induced MPNs,” the authors of the study wrote in their report. “Additional mutations or genetic abnormalities are required in association with SRSF2P95H and JAK2V617F mutations in the development of full-blown myelofibrosis.”

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Merck Announces Phase 3 Trial Initiations for Four Investigational Candidates From its Promising Hematology and Oncology Pipeline

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January 5, 2024 6:45 am ET

Global Phase 3 studies started for bomedemstat (LSD1 inhibitor), nemtabrutinib (BTK inhibitor), MK-2870 (anti-TROP2 ADC) and MK-5684 (CYP11A1 inhibitor)

Comprehensive clinical development programs being initiated for each investigational candidate

Demonstrates company’s commitment to research across novel mechanisms of action in hematologic neoplasms/malignancies, as well as lung, endometrial and prostate cancers

RAHWAY, N.J.–(BUSINESS WIRE)– Merck (NYSE: MRK), known as MSD outside of the United States and Canada, today announced the initiation of pivotal Phase 3 trials for four of its investigational candidates from its diverse pipeline in hematologic malignancies and solid tumors. Global Phase 3 studies have been initiated and are actively enrolling for the following investigational candidates:

  • Bomedemstat, an investigational orally available lysine-specific demethylase 1 (LSD1) inhibitor, being evaluated for the treatment of certain patients with essential thrombocythemia (ET);
  • Nemtabrutinib, an investigational oral, reversible, non-covalent Bruton’s tyrosine kinase (BTK) inhibitor, being evaluated for the treatment of certain patients with chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL);
  • MK-2870, an investigational trophoblast cell-surface antigen 2 (TROP2)-directed antibody drug conjugate (ADC) being developed in collaboration with Kelun-Biotech, which is being evaluated for certain patients with non-small cell lung cancer (NSCLC) and certain patients with previously treated endometrial carcinoma;
  • and MK-5684, an investigational CYP11A1 inhibitor being developed in collaboration with Orion, which is being evaluated for the treatment of certain patients with metastatic castration-resistant prostate cancer (mCRPC).

“These Phase 3 trial initiations for four of our investigational candidates represent a critical step forward in our efforts to advance potential treatment options for people with solid tumors and hematologic neoplasms and malignancies,” said Dr. Marjorie Green, senior vice president and head of oncology, global clinical development, Merck Research Laboratories. “We have a proud legacy of turning breakthrough science into medicines that save and improve lives around the world, and we are dedicated to continuing research to expand our broad portfolio of oncology therapeutics to continue to address unmet needs in cancer care.”

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Patients With MPNs Face a Heighted Risk for Thrombotic, Cardiovascular Events

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Alex Biese
Patients with myeloproliferative neoplasms (MPNs) — a group of blood cancers that causes the bone marrow to overproduce red or white blood cells or platelets (including polycythemia vera, essential thrombocythemia and myelofibrosis) — face a height risk for thrombotic and cardiovascular events.

But Kim Noonan, DNP, ANP-BC, AOCN, FAAN, Nursing and Patient Care Services Chief Nurse Practitioner at the Dana-Farber Cancer Institute in Boston, said there are things nurses can do to help manage that risk, such as inquiring about patients’ history of blood clots and encouraging patients to not be sedentary, as well as watching for symptoms such as elevated heart rate and shortness of breath.

“I am always thinking about thrombosis first, and then I can relax if I have maybe another explanation for their shortness of breath,” Noonan said. “But we’re always working it up, we really do due diligence to not miss some kind of thrombotic event that’s going on.”

Noonan spoke with Oncology Nursing News about awareness of the potential for thrombotic and cardiovascular events, risk factors to be mindful of and everyday actions patients can take to lower their risk.

Transcript:

Noonan: NCCN, the National Comprehensive Cancer Network, really has done a lot of work in identifying this for multiple myeloma patients, and they actually have come up with guidelines as to who really needs to be on anticoagulant therapy and who does not, and they’ve identified factors that we need to consider. And so, I think it’s getting a lot of press, it’s getting a lot of attention, certainly in the myeloma world. But I think it deserves a little bit more attention, I hate to say it, but maybe in solid tumor worlds as well.

One of the things that I didn’t mention was that, I think I said people that are dehydrated are at risk, but also people that have been on like airplane rides, people that have been in long car rides, too, are really at risk. So those are other risk factors that I think I failed to mention.

Oncology Nursing News: Would working a sedentary job, such as a desk job, also potentially be a risk factor as well?

Noonan: That’s a huge risk factor, as well, to the point of, we say to people, if you’re not getting up and walking around, maybe we should consider putting you on anticoagulation therapy right up front as opposed to just using an aspirin.

Oncology Nursing News: What are some simple things, such as getting up and walking around, that folks can do in their everyday lives to lower their risk?

Noonan: Yeah, that’s a really good question. We really want people to stay hydrated. We want them to get up and walk around. We want them to be aware of what the symptoms are, they can be doing everything right and still develop a clot because of the medication that they’re on.

But I think also, education is essential, that you are on a medication that can increase your chances of developing a clot or thrombosis, and just be aware of what the symptoms are.

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A Patients Speaks Out About Her Experience With MPN Symptoms

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Darlene Dobkowski, MA

Fatigue, pain, and itchiness are often some of the most troublesome symptoms patients with a myeloproliferative neoplasm (MPN) faces, according to Jessica Kuhns.

Kuhns, a 42-year-old woman with an MPN, spoke with Oncology Nursing News about receiving her diagnosis in 2016 and how nurses have helped her manage her symptoms. Despite a high turnover rate of nurses, she appreciates their collective efforts.

Oncology Nursing News: Tell me about yourself.

Kuhns: My name is Jessica Kuhns. I’m 42 years old. My biggest accomplishment is my son Jaden. We’re kind of a tag team. Everything I do, he’s right there with me. Whatever he does, I do with him. In 2016, I was diagnosed with MPN. I’ve been fighting it ever since and doing the best I can day by day.

Can you tell us about when you were diagnosed?

It all started with a magnetic resonance imaging [MRI] test on my knee, believe it or not. TIn the MRI, they saw that my spleen was severely enlarged. They wanted me to go to a hematologist. I started seeing a doctor in Pennsylvania, where I live. I had just had a hysterectomy. I had just beaten uterine cancer in 2015. And she had assured me the doctor that, after the hysterectomy and a splenectomy that my iron levels — because I had very low iron as well —would go back to normal. It would be a better thing for me to have my spleen removed. So I said OK.

I went and I had the procedure. They actually screwed it up really bad and I darn near died. They started out laparoscopically, but they cut out a major artery and I started bleeding out. Then I developed a massive, massive blood clot that consumed 3 major return veins from my intestines. The doctors had told my husband, at that time, and my son to start making my final arrangements, and that they didn’t see me walking out of the hospital.

I was then introduced to my now-doctor, and he came in like a wrecking ball. He was like, I’m your doctor, and I think I have an idea of what’s going on. As long as you’re willing to fight, I’m going to fight with you. And we have. He got me out of the hospital. My platelets were at 1.9 million. He got them under control, and back down to a “normal range.” I was able to leave the hospital and I’ve been great since.

You mentioned some side effects that you encountered since you were diagnosed. Were there any other ones outside of the surgical procedure that you’ve experienced?

Yeah, there are definitely side effects from this disease. The 3 top complaints, which are my 3 top complaints, are fatigue, pain, and itchiness. Those are the three that I most complain of. Mine are definitely pain, fatigue, and I do get itchy, but I don’t know if it’s because of the changing of the seasons or if it’s from the MPN. I hate to blame everything on MPN.

How have nurses helped you address those side effects and to potentially manage them?

They have absolutely directed me in the right way, as far as finding resources, and what will help and what makes it worse. They’ve done a great job in guiding me to find the information that I needed.

Is there a certain moment that stands out to you when a nurse has helped you?

Not one that stands out too much. I mean, unfortunately, such a high turn rate of nurses, it’s really sad. So I can’t say that I’ve had one specific nurse or one specific instance that I was like, Oh, wow, this is amazing. But I have had moments where my nurses did amazing things for me.

Was there ever advice that a nurse may have given you that really helped you?

They just always encouraged me to stay as positive as I can. I know it sounds corny, but the more positive you stay, the better chances you have of fighting this. They encourage you to keep going because there are times where like, oh, this is just so frustrating. And they’re just right there pushing you along, like you got this.

What advice would you give to both patients and nurses?

I think the nurses are doing great listening to us, I don’t think that’s the problem. Unfortunately, like I said, with such a high turn rate, you don’t see the same nurse repeatedly. Every nurse that I’ve ever come across is really in it for the patients. They are so knowledgeable, they’re so there.

And as far as the patients, have that communication with your nurses, talk to them. You may not see them on your next appointment, but they’ll give you whatever information that you need.

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Community Helped a Patient When Their MPN Treatment Was Delayed

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Brielle Benyon

Thomas Silver discusses how a community of support helped a patient when his bone marrow transplant was delayed.

Undergoing treatment for a myeloproliferative neoplasm (MPN) can be extremely lonely, so it is beneficial to have a support system throughout the process, explained Thomas Silver, board president of the Cancer Research and Treatment Fund in New York.

Silver, who was also recognized at CURE®’s 11th annual MPN Heroes® recognition event, told the story of his friend, Nick, an MPN survivor who was preparing to undergo a bone marrow transplant — which is currently the only curative therapy for MPNs — before he caught a common cold and had to have the procedure pushed back.

“Well, a month in his life is a long time,” Silver said.

However, Nick, Silver and a group of others are a part of a community that was able to offer support and stay in touch with Nick, who eventually went on to receive the transplant and is doing well, according to Silver.

Transcript

Well, it can be fairly lonely. It’s a really long, hard task. I remember talking to Nick when he was going through his through his trials and his journey. One of the things that happened was he was all ready to go with his transplant. And just a week or two beforehand, he developed a common cold and imagine being ready to go. And then you develop a cold. And they say, “Well, now because you have cold, you’ve got to wait another month.”

Well, a month in his life is a long time. So, the fact that we were around, we were available to talk to him, Nick and I are part of a large fraternity house and we have a number of brothers that we continue to stay in touch with. You have a great time with all the time. Just help him keep his spirits up when he was waiting that extra month to be able to actually begin the process of getting better.

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Management of Ruxolitinib in MF Allows for Continued Survival Benefit

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Targeted Oncology Staff

In the second article of a 2-part series, Pankit Vachhani, MD, highlights the impact ruxolitinib has had, and continues, to have in treatment for patients with myelofibrosis and how physicians should manage this treatment for their patients.

CASE

  • A 68-year-old woman presented to her physician with symptoms of mild fatigue.
  • Her spleen was palpable 6-7 cm below the left costal margin​.
  • Medical history: No known comorbidities
  • Next-generation sequence testing: JAK2 V617F mutation​
  • Karyotype: 46XX​
  • Bone marrow biopsy: megakaryocyte proliferation and atypia with evidence of reticulin fibrosis​
  • Blood smear: leukoerythroblastosis​
  • Diagnosis: Primary myelofibrosis​ (MF)
  • Dynamic International Prognostic Scoring System: intermediate-1​
  • Mutation-enhanced International Prognostic Score System 70: intermediate risk
  • The patient was not interested in transplant​.
  • A decision was made to initiate ruxolitinib (Jakafi).

Targeted Oncology: For patients with MF, what were their symptom responses while on ruxolitinib (Jakafi)?

PANKIT VACHHANI, MD: The patient’s symptom responses were recorded using different Quality of Life questionnaires from COMFORT-II study [NCT00934544].1 Patients on ruxolitinib did better with overall quality of life or functioning, as well as in some individual categories like pain, fatigue, and dyspnea. We also had data from COMFORT-I [NCT00952289], which used a symptom assessment form, [that showed similar results].2

How did the survival data compare between these 2 trials?

COMFORT-I had an inherent crossover designed into it. After 6 months, or 24 weeks, patients who got placebo could cross over to ruxolitinib, and the majority did so.2 Despite that, [we saw] the overall survival [OS] favored the patients who were originally randomized to ruxolitinib vs those who were originally randomized to placebo. That HR of 0.69 [95% CI, 0.50-0.95; P = .025] tells the story, in this case, and the OS data from COMFORT-II had an HR of 0.48 [95% CI, 0.28-0.85; P = .009]….3 These data are all pointing towards a survival advantage for patients who go on ruxolitinib. It’s important to note that there are survival data, but it was not the primary end point; it was the secondary endpoint, and it has been studied elsewhere as well.

How did the duration of treatment with ruxolitinib impact results for these patients?

[With ruxolitinib, we all ask] when should we begin treatment. Well, this was studied indirectly. The patients who went on the COMFORT studies were pooled together, so all the patients who were on ruxolitinib between these 2 studies were pulled together and [patients given] placebo and best available therapy were pooled on the other side.4 In terms of OS, if ruxolitinib was begun within 12 months of their MF diagnosis, those patients did the best in terms of survival, compared with patients who began ruxolitinib a little bit later, [at least] more than a year after diagnose [odds ratio (OR), 2.08; 95% CI, 1.12-3.90]. That’s an important point, which is [suggesting that] maybe beginning ruxolitinib treatment early might be associated with a better survival outcome. Similarly, the spleen volume responses…were also better for those who begin ruxolitinib earlier rather than later [at 47.6% vs 32.9%, respectively (P = .06)], which is also important to keep in mind [when treating these patients].4

What are the major hematologic adverse events (AEs) physicians should be aware of when using ruxolitinib?

In both COMFORT-I and COMFORT-II, cytopenias were some of the more common AEs. Grade 3/4 anemia, for example, with ruxolitinib was seen in 45% and 42% [of patients] and thrombocytopenia in 13% and 8%, [respectively].1,2 These can be managed through either transfusion, a drug hold, or maybe dose reductions, but the point is that [these AEs are] ruxolitinib related, [possibly due to the] inhibition of the JAK-STAT pathway.

The concern that I’ve heard from many is if [the patient] starts off with anemia, are they not responding as well [to ruxolitinib] compared with those who don’t start off with anemia? Or just the fact that ruxolitinib can cause anemia, does it make the overall outcomes worse? The answer is that ruxolitinib will lead to comparable outcomes, whether [the patient] has anemia or not.2 The spleen responses will be comparable, similarly and the symptom responses will be comparable. The underlying point is that the efficacy is maintained in patients with new onset anemia. We must separate drug-induced anemia of ruxolitinib, with the bad effects of anemia from MF, as these are 2 different types.

References:

1. Harrison C, Kiladjian JJ, Al-Ali HK, et al. JAK inhibition with ruxolitinib versus best available therapy for myelofibrosis. N Engl J Med. 2012;366(9):787-98. doi:10.1056/NEJMoa1110556

2. Verstovsek S, Mesa RA, Gotlib J, et al. A double-blind, placebo-controlled trial of ruxolitinib for myelofibrosis. N Engl J Med. 2012;366(9):799-807. doi:10.1056/NEJMoa1110557

3. Cervantes F, Vannucchi AM, Kiladjian JJ, et al; COMFORT-II investigators. Three-year efficacy, safety, and survival findings from COMFORT-II, a phase 3 study comparing ruxolitinib with best available therapy for myelofibrosis. Blood. 2013;122(25):4047-53. doi:10.1182/blood-2013-02-485888

4. Verstovsek S, Kiladjian JJ, Vannucchi A, et al. Early intervention in myelofibrosis and impact on outcomes: A pooled analysis of the COMFORT‐I and COMFORT‐II studies. Cancer. 2023;129:1681-1690. doi:10.1002/cncr.34707

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AI Tool Accurately Differentiates MPNs Using Bone Marrow Biopsies

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Jordyn Sava

Andrew Srisuwananukorn, MD, assistant professor at The Ohio State University Comprehensive Cancer Center, discussed the use of a novel artificial intelligence model that aids in the differentiating between prefibrotic primary myelofibrosis and essential thrombocythemia.

An artificial intelligence (AI) model is being investigated that will help clinicians distinguish between prefibrotic primary myelofibrosis (pre-PMF) and essential thrombocythemia (ET) using bone marrow biopsy images from 200 patients.

The AI tool had previously been trained with 32,000 pan-cancer biopsy images. It was also familiar with general pathologic features. From this, investigators tested if the AI could differentiate between the 2 types of myeloproliferative neoplasms (MPNs) in patients.

According to findings presented by Andrew Srisuwananukorn, MD, at the American Society of Hematology 2023 Meeting, the tool demonstrated a 92.3% rate of agreement with human experts, and the sensitivity and specificity for pre-PMF diagnosis was 66.6% and 100%, respectively.

Based on these promising findings, experts will continue to update the AI tool and test it in larger data sets.

“I view this type of tool as a companion diagnostic tool, but I do not believe [that] AI tools can replace the judgment of a human physician. I think it is really up to us as pathologists and clinicians to say when an AI algorithm tool is not working appropriately. What I hope is that this can be used for better information for the patient to understand their disease,” said Srisuwananukorn, assistant professor at The Ohio State University Comprehensive Cancer Center, in an interview with Targeted OncologyTM.

In the interview, Srisuwananukorn discussed the use of a novel AI model that aids in the differentiating between prefibrotic primary myelofibrosis and essential thrombocythemia.

Targeted Oncology: What can you tell us about this AI tool?

Srisuwananukorn: Our research is in developing an artificial intelligence tool to differentiate between rare myeloid malignancies, including prefibrotic myelofibrosis and essential thrombocythemia. As a brief overview, these diagnoses are challenging to differentiate because there’s similar criteria, including clinical and laboratory abnormalities, mutational profiling, and assessment of the bone marrow, which can be very subjective, particularly when looking at the megakaryocyte morphologies in the fibrosis. Our hope is to create a more objective or at least consistent tool using artificial intelligence to differentiate between the 2.

What is the motivation behind the development of this tool? What specific challenges or clinical needs there are in distinguishing between different disease types?

Our motivation is that this is a diagnostic dilemma for our patients. Essential thrombocythemia and prefibrotic primary myelofibrosis behave quite differently. The prefibrotic myelofibrosis cases have more symptoms and are at higher risk for progression to acute myeloid leukemia. To me, it behooves the physician to know exactly which disease they have. It’ll help guide their therapies in the future. Our hope is that a tool such as this can help guide that management and potentially to help enroll in clinical trials for more appropriate diagnosis and therapy creations.

In your study, how did AI demonstrate its efficacy when differentiating between the myelofibrosis and ET?

Our model had very high performance with [an] area under the receiver operator curve of 0.9, a sensitivity of 66.6% specificity of 100%, and an accuracy of 92.3% in diagnosing prefibrotic myelofibrosis. In addition, we did a qualitative analysis to try to understand what is being used in these AI algorithms to make those predictions. With this qualitative interpretation of quote unquote, opening the black box of our AI algorithms, we were able to see that preferentially, areas of bone marrow cellularity were chosen for the prediction of 1 vs the other disease. Reassuringly, the algorithm was not using nonsensical portions of the image, such as fat or cortical bone or even background artifacts. We believe this AI algorithm is using biological reasons.

What distinguishes this tool from others and how can it be interpreted in these settings moving forward?

I view this type of tool as a companion diagnostic tool, but I do not believe [that] AI tools can replace the judgment of a human physician. I think it is really up to us as pathologists and clinicians to say when an AI algorithm tool is not working appropriately. What I hope is that this can be used for better information for the patient to understand their disease.

Are there any particular patient subgroups that the AI tools showed notable effectiveness?

For right now, we’re only looking at 2 particular diseases: prefibrotic myelofibrosis and essential thrombocythemia. However, that does not mean that this is our only goal. These algorithms are agnostic of disease and outcome. Potentially, the same types of algorithms or workflows can be used for any type of disease that other clinicians might be able to implement in their clinical practice. Our particular goal is to do better for patients [with MPNs], and we have multiple ideas of how we can do that.

Moving forward, what are some of the next steps for this research?

Our next steps are in 2 domains. One, for this particular algorithm in differentiating pre-PMF and ET, we hope to validate it in further, larger retrospective cohorts at other academic centers and potentially within clinical trials that enroll patients [with ET]. Our thought is potentially, the ET trials did not have great performance because they were accidentally enrolling these pre-PMF cases. That’s our next step into rigorously seeing if this algorithm can be effective. Outside of that, we’re hoping that we can develop similar algorithms in other outcomes of interest, including risk stratification and therapy response.

What should oncologists know about the growing use of AI?

For physicians at large, what I want to reiterate is that it is important that we understand how it’s being used and when to use it. I do not believe that algorithms can supplant physician judgment, but I do think that they will be used in clinical practice and it’s up for us to know when it’s not working. I hope that it’s a support tool and will help guide your decision management but it’s always up to the physician.

REFERENCE
Srisuwananukorn A, Loscocco GG, Kuykendall AT, et al. Interpretable Artificial Intelligence (AI) Differentiates Prefibrotic Primary Myelofibrosis (prePMF) from Essential Thrombocythemia (ET): A Multi-Center Study of a New Clinical Decision Support Tool. Blood. 2023;142(suppl 1): 901.doi:10.1182/blood-2023-173877

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MPN Outcomes Have Improved in the Last 20 Years

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Brielle Benyon

Years ago, when Dr. Shamim Salman started treating patients with myeloproliferative neoplasms (MPNs), she, unfortunately saw many patients die from the disease because there was limited knowledge and treatment options.

However, outcomes are much better now with the advent of new therapies such as JAK inhibitors, Salman, hematologist-oncologist at Richmond University Medical Center in Staten Island, New York, said in an interview with CURE®.

“But now I’ve seen so many new things, so much research, so many new drugs and I’m so happy about it,” Salman, who was also honored at the 11th annual MPN Heroes® recognition event. “My patients are living longer. I feel so happy.”

Transcription

I have seen with my own eyes so many patients are dying with myeloproliferative neoplasms, especially I will mention myelofibrosis. I had so many patients (die because) at that time (when I started), there was no (knowledge of) JAK2, no JAK inhibitors, nothing. And patients would ask me, or their daughters or their sons (would ask), “Doctor, you will do something, right? You will make my mom better?” And I would say, “We will try.”

But now I’ve seen so many new things, so much research, so many new drugs and I’m so happy about it. My patients are living longer. I feel so happy. My patients 20 years ago, they died much sooner. They couldn’t see their granddaughter’s wedding or whatever their dreams were. Sometimes, I cried for them because I knew there’s nothing.

Not everybody was eligible for bone marrow transplant because some of them were elderly. Bone marrow transplant was there. I have sent my patient with myelofibrosis for bone marrow transplant. But unfortunately, if they were elderly, they died of the complications. So I tell my fellows, “You guys are so lucky now, so many drugs, so many research, so many things going on.”

And usually, my style is if I see a case, I tell them, go read about it today. And by the end of the day, again, we will talk and do look for clinical trials, look for the new research. I’m in Staten Island, but I’m connected with all the big institutions. And from the day one, we try to do the right thing for them.

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How I Treat: Myeloproliferative Neoplasms in Pregnancy

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Susan Robinson, Monica Ragheb, Claire N. Harrison
December 25, 2023
Whilst MPN are traditionally considered diseases of adults in their sixth or seventh decade these conditions do occur in young patients for example for essential thrombocythaemia in particular there is a second peak in women of reproductive age. Pregnancy therefore is an uncommon but not rare occurrence and clinical challenge in some scenarios. Here we discuss in detail our local approach to the management of pregnancy in MPN patients taking a case-based approach. We take time to include relevant updates in the field and point to a future research strategy which should be internationally focused in order to obtain as much information in as short a time as possible.

What is Cytoreduction in MPNs?

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Alex Biese

Dr. Douglas Tremblay of the Ichan School of Medicine explains the necessity of cytoreductive therapy for patients with MPNs such as essential thrombocythemia and polycythemia vera.

Cytoreduction is crucial for preventing serious complications for patients with essential thrombocythemia (ET) and polycythemia vera (PV) — both types of blood cancers that fall under the category of myeloproliferative neoplasms (MPNs), as Dr. Douglas Tremblay, explained in an interview during the 65th American Society of Hematology (ASH) Annual Meeting.

“Thrombosis is the leading cause of morbidity and mortality in patients with polycythemia vera and essential thrombocythemia, and these (cytoreductive therapy) medications are given in order to mitigate that risk,” said Tremblay, an assistant professor of medicine at the Icahn School of Medicine at Mount Sinai in New York City.

Tremblay, writing in Hematology, ASH Education Program, explained that approved treatments for cytoreduction among patients with ET and PV include hydroxyurea and long-acting interferons, plus anagrelide for patients with ET and Jakafi (ruxolitinib) for those with PV.

Tremblay discussed cytoreductive therapy, when it is best to start treatment and support services that are available for patients.

Q: Can you discuss what cytoreduction is and how it works for ET and PV?

A: Cytoreductive therapy refers to multiple medications which are given with the purpose of reducing blood counts in both essential thrombocythemia and polycythemia vera but are also given for the purpose of reducing thrombotic risk, which, thrombosis is the leading cause of morbidity and mortality in patients with polycythemia vera and essential thrombocythemia, and these medications are given to mitigate that risk.

Q: What factors influence the decision to recommend cytoreduction for these patients?

A: The discussion around when to start cytoreductive therapy around chronic MPN patients (with) PV and ET really has to do with risk stratification and the risk stratification scheme is available (and) largely used through the ELN risk classification, which dictates (that) high-risk patients older than an age of 60 or those who have a prior thrombosis. And, in ET, there are additional risk stratification schemas, including the IPSET-thrombosis (model) and the revised subset thrombosis score.

These can dictate which patients are at high risk for thrombosis and (who) then would benefit from cytoreductive therapy. But many of these different factors exist on a continuum such as age in particular, and what I highlighted in my talk (as ASH) is that there’s no difference in your risk stratification (on) the day that you turn 61 years old. It’s very important to understand someone’s biological age, including their cardiovascular risk factors, that can inform their overall risk of having a blood clot in these diseases.

Q: What support services can be made available for patients during and after cytoreductive treatment?

A: I think a lot of support services for patients with PV and ET during cytoreductive therapy really revolve around mitigating toxicities and trying to understand what some of these toxicities are. And I think it’s really helpful to partner with your physician to try to understand what sort of additional resources are available.

Some of these medications, (they) can also have a high financial cost too. There are support services available to help patients who are eligible to try to enjoy the benefits of some of these newer medications to improve their outcomes.

A lot of treatment of PV and ET really involves more of a holistic approach and not just focusing on the blood counts, but really focusing on other parameters that each patient has and trying to optimize those in order to ensure the best long-term outcomes.

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