Sunday May 1, 2022

Presenter: Paul Shaughnessy MD, Sarah Cannon Transplant and Cellular Therapy Program at Methodist Hospital, San Antonio, Texas.

Presentation is 32 minutes long with 23 minutes of Q & A.

Summary: Half of patients who have a stem cell transplant using donor cells (an allogeneic transplant) develop chronic graft-versus-host-disease (GVHD). In up to a third of those patients, GVHD affects the mouth, esophagus, stomach and/or GI tract. GVHD can also affect the liver and/or pancreas. This presentation describes the symptoms and treatment options for GI and liver GVHD.

Highlights:

• Up to a third of patients with chronic GVHD have symptoms in the esophagus, stomach and/or lower GI tract. Symptoms include stomach upset, diarrhea, difficulty swallowing, malabsorption and weight loss.
• GVHD can damage the GI tract and enable bad bacteria to outnumber beneficial bacteria, which can lead to more GVHD and worse outcomes.
• Jakafi® and Rezurock® have recently been approved by the FDA to treat GVHD that does not respond to steroids. Extracorproeal photopheresis (ECP) also helps some patients with GI GVHD.

Key Points:

(08:36): Use of very broad-spectrum antibiotics after transplant can destroy the good bacteria in our bowels and lead to more GVHD.

(11:46): GVHD can damage saliva glands in the mouth, causing dry mouth, mouth sores and an increased risk of cavities or periodontal disease

(13:32): Saliva substitutes can help people who have a dry mouth. If people have pain or cannot eat, Decadron® and tacrolimus rinses can help.

(17:15): GVHD can affect the pancreas, the organ that makes enzymes to helps digest food, causing fat and undigested food in the stool.

(20:39): GVHD can cause strictures in the esophagus which can make swallowing difficult. A procedure called esophageal dilation can help.

(22:21) Jaundice and an increase in bilirubin may be a sign of GVHD in the liver, which can interfere with the digestion of food.

(25:29): Mild or moderate GVHD may be treated with localized or topical agents. Severe GVHD is typically treated with systemic corticosteroids or calcineurin inhibitors.

(26:24): Jakafi®and Rezurock® have recently been approved by the FDA to treat GVHD that does not respond to steroids.

(28:14): Extracorporeal photopheresis, which is FDA-approved for patients with cutaneous T-cell lymphoma, can also help patients with GI or liver GVHD

(30:30): Several specialists including dentists, gastroenterologist, nutritionists and physical therapist may be needed to effectively treat GVHD.

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Friday, August 12, 2022 at 4:05 PM

– Positive Data from the Ongoing Phase 2 Study of Bomedemstat in Essential Thrombocythemia (ET) Presented at European Hematology Association (EHA) Meeting 2022 –

– Positive Data from the Ongoing Phase 2 Study of Bomedemstat in Advanced Myelofibrosis Presented at EHA 2022 –

– First Participant Dosed in Investigator-Sponsored Phase 1/2 Study of Bomedemstat in Combination with Atezolizumab in Small Cell Lung Cancer –

– Obtained Advice from FDA Clinical Outcomes Assessment (COA) Group with Regard to Patient Reported Outcome (PRO) Endpoints for the Company’s Planned Phase 3 Trial of Bomedemstat in ET Patients –

SOUTH SAN FRANCISCO, Calif., Aug. 12, 2022 (GLOBE NEWSWIRE) — Imago BioSciences, Inc. (“Imago” or the “Company”) (Nasdaq: IMGO), a clinical-stage biopharmaceutical company discovering and developing new medicines for the treatment of myeloproliferative neoplasms (MPNs) and other bone marrow diseases, today reported financial results for the second quarter ended June 30, 2022 and provided business updates.

“We were delighted to present updated positive data on our Phase 2 trial of bomedemstat in essential thrombocythemia (ET) at EHA in June. In our updated dataset, bomedemstat demonstrated hematologic and symptomatic improvement in ET patients and, importantly, demonstrated the durability of these hematologic responses. These data will support our ongoing discussions with the FDA, as we target an End of Phase 2 meeting with the FDA later this year, and move towards initiating the pivotal trial,” said Hugh Young Rienhoff, Jr., M.D, Chief Executive Officer of Imago.

“At EHA, we also presented positive data from our advanced myelofibrosis (MF) Phase 2 trial where bomedemstat demonstrated improvements in total symptom scores, fibrosis grades, spleen volumes and anemia, as well as reductions in mutant allele frequencies. Looking ahead, we plan to evaluate bomedemstat in combination with ruxolitinib in MF patients in a trial starting in the Fall 2022. Lastly, in addition to our long-held plans to study bomedemstat in other myeloproliferative neoplasms, such as polycythemia vera, we were pleased to see initiation of the first solid tumor clinical study of bomedemstat, an investigator-sponsored study of bomedemstat in combination with atezolizumab for small cell lung cancer.”

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August 10, 2022
Jennifer Larson

Myeloproliferative neoplasms (MPNs) are uncommon in children and young people. As a result, the guidelines currently used to reduce the risk of thrombosis and hemorrhage in patients with MPNs are based on literature involving patients over the age of 60.

A team of researchers set out to learn more about children and young adults with MPNs, due to the lack of sparse existing data. They published their findings in Blood Advances.

The researchers conducted a retrospective study that included members of the European Hematology Association MPN scientific working group who were diagnosed with an MPN before the age of 25. They examined data from 444 patients from 15 countries, 53.8% of who were diagnosed between the ages of 20 and 25.

They confirmed that the most common MPN subtype was essential thrombocythemia (ET), representing 71.6% of this cohort. Another 18.2% had the polycythemia vera (PV) subtype, and the remaining had primary myelofibrosis (PMF), prefibrotic myelofibrosis (PreMF), or unclassified MPN (MPN-u).

They also found what they called “interesting perspectives on how these MPN are perceived by physicians” and how they are managed. “Importantly, we demonstrate that standard prognostic scores do not perform well in this cohort,” they wrote. “As an example, 67.8% received at least one cytoreductive drug when only 21.4% of them should have received such therapy according to currently [European LeukemiaNet (ELN)] recommendations.”

They added that the proportion of certain prescriptions for the participants also suggested that their physicians didn’t apply ELN recommendations “where interferon is the recommended first-line therapy in patients aged below 60 years old because of its lack of leukemogenicity  and its low teratogenicity.” But as they noted, no MPN guidelines exist for children or adolescents, so the differences likely reflect “historical shifts in guidelines and availability of therapy.”

The researchers also uncovered higher-than-anticipated rates of thrombosis, hemorrhage, and transformation in their real-world cohort compared with the rates in their literature review. And 11% of patients had a history of thrombotic events, especially in patients with PV (21.5%).

“Due to the predominance of venous events, classical management with low-dose aspirin to prevent thrombosis should perhaps be questioned in this specific population, as it mainly reduces the risk of arterial events,” the researchers wrote. “The use of anticoagulants could be a way to reduce the incidence of venous thrombotic events.”

The study did have limitations, such as its retrospective nature, which may have resulted in some biases. Also, without specific treatment guidelines for young patients, the management could have been heterogeneous among the various centers, which could have influenced the rate of complications. However, they did point out that they had a “very high number of such extremely rare patients….suggesting that we revealed a reliable picture of MPN in very young patients.”

Ultimately, the research revealed a high disease burden with incidences of thrombotic events and transformations that were higher than previously reported in this particular population. The information could be used for future biomarkers studies, clinical trials, and the creation specific treatment guidelines for younger MPN patients.

Disclosures: Some authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

Reference

Sobas M, Kiladjian J, Beauverd Y, et al. Real world study of children and young adults with myeloproliferative neoplasms identifying risks and unmet needs. Blood Adv. Published online July 8, 2022. doi:10.1182/bloodadvances.2022007201

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August 3, 2022

Experts discuss data on the recently approved agents fedratinib and pacritinib for myelofibrosis treatment.

Rami Komrokji, MD: There’s no doubt that ruxolitinib was transformative for our patients. It’s still a mainstay in treatment for many patients, especially upfront, but there are areas of unmet need in patients who are cytopenic. Ruxolitinib failure is still an issue for a lot of our patients. Recently it was exciting for our patients that there were 2 new drugs approved: fedratinib, with an interesting comeback, and pacritinib, for which Ruben and I did the phase 1 probably 10 years ago. It took the drug a while to get approved, but it finally is. Ruben, can you walk us through fedratinib and pacritinib and where you see their role now that they’re available for our patients?

Ruben Mesa, MD: Sure. It’s good that we have more options, and exciting that we now have 3 approved drugs in myelofibrosis [MF]. In the…community, we haven’t had an opportunity to use either of these. Let me share a little about what we think about each of them. First, fedratinib is a very good JAK inhibitor—JAK2, FLT-3—approved from the JAKARTA (NCT01437787) and JAKARTA-2 (NCT01523171) studies. JAKARTA studied it front line, and JAKARTA-2 in second line vs placebo in the front line. It was a study almost parallel with the COMFORT study. It’s clearly superior to placebo for improving the spleen and symptoms, and as far as adverse effects, it didn’t cause cytopenias.

The approval of the drug was delayed because there was a very low rate of Wernicke encephalopathy, probably interfering with thiamine metabolism to a small degree. There’s a black box warning that sounds pretty scary but in practice is fairly simple. You check thiamine levels and you replace thiamine, and thiamine is dirt cheap. I give patients a bottle. Then you monitor for Wernicke. That’s pretty small. The more likely adverse effects can be GI [gastrointestinal]. I give some folks some antinausea, some antidiarrhea medications. They can take it. It’s very helpful in the second line.

If they used ruxolitinib and still have [an enlarged] spleen and symptoms, and you don’t have a trial available, fedratinib is a good option. It can be used at full dose in patients with platelets between 50,000 and 100,000 per mm3. I helped present some of those data. It’s a very solid option, with a couple of those small caveats. It was approved in fall of 2019 just before the pandemic, so folks still have less familiarity with it.

Much more recently, pacritinib has a long history. We noticed early on when we did that phase 1—back when it called SB1518—that you could use it irrespective of platelet count. You could use it in marked thrombocytopenia. Over time, a mechanism was found explaining why that could be the case. It inhibits IRAK1. It might be better for patients with cytopenic MF. In critical studies, it could be used safely and effectively in individuals with platelet counts of less than 50,000 per mm3. It’s approved for individuals with marked thrombocytopenia in the front line and second line. It might also help to improve anemia.

It has been approved since February 2022. It’s a good option. It will be used either up front or more frequently in the second line to be that thrombocytopenic. It’s already being woven into the NCCN [National Comprehensive Cancer Network] Guidelines in a group that didn’t have an option before. It will be well positioned for combination strategies. Many of the drugs that have different mechanisms of action also tend to cause thrombocytopenia, so it might be a very nice adjunct for that.

People sometimes say: “Myelofibrosis isn’t that common. Can we have all these drugs?” Yes. The more options we have, the better. These drugs will end up having ranges of use in a range of diseases, including anti-inflammatory diseases, cutaneous diseases, and rheumatologic diseases. You don’t have to worry about the drug not having enough patients. But even though myelofibrosis isn’t common, it can be pretty heterogenous. We have MPN [myeloproliferative neoplasm] and MDS [myelodysplastic syndromes] overlap. We’ve got patients with ET [essential thrombocythemia] and PV [polycythemia vera]. The more options we have, the better.

Rami Komrokji, MD: I absolutely agree. Cytopenic MF is a challenging disease. As you alluded to, most of the time we deal with it later in the course of the disease as a natural history of progression. But there’s a subset of up to 20% of those patients, even upfront, that has limited the use of ruxolitinib in that setting. To your point also, we’ve been exploring those drugs in other diseases. We have ongoing trials in CMML [chronic myelomonocytic leukemia] with JAK2 inhibitors and other types of MDS and MPN. It’s always exciting to have more options that fill different gaps of unmet need for our patients.

Jeanne Palmer, MD: We also know that the role of JAK inhibitors prior to transplant can be very beneficial. It has been studied being used 2 months before transplant up until the time of transplant, and even through transplant up until engraftment or day 30. There’s even 1 study looking at it for 1 year. Additionally, after transplant, these drugs can treat graft-vs-host disease. In some of the studies, there are prophylactic studies using JAK inhibitors for all patients. But it’s a gray area for patients who have myelofibrosis who have been on them, because the worst thing you can do is taper them off their JAK inhibitor right before transplant. That causes them to flare up and have lots of transplant complications.

Rami Komrokji, MD: Before the JAK inhibitor era, we couldn’t take many patients to transplant because of how much they were deconditioned. We used to even talk sometimes about doing splenectomy before transplant. Now, when those drugs work, the patient’s performance improves and their spleen shrinks, so it’s good preparation for the transplant. But to your point, even at our institution, we have a protocol where we don’t stop those drugs. You keep [patients on them] until the transplant because patients will have a quick rebound of their symptoms.

Transcript edited for clarity.

Rami Komrokji, MD: Let’s talk about myelofibrosis [MF]. Of those diseases, this is probably the most symptomatic disease, with a high burden on patients and worse outcome in general. Jamile, can you walk us through myelofibrosis? How do we diagnose, differentiate, and approach it? How do you risk stratify those patients?

Jamile Shammo, MD, FACP, FASCP: Myelofibrosis is the MPN [myeloproliferative neoplasm] associated with the worst outcome. It’s so critical to identify it right away. The most challenging piece about myelofibrosis is getting the doctors to do a bone marrow biopsy, because the only way to make a diagnosis of myelofibrosis is by demonstrating that you have 2- or 3-plus reticulin fibrosis. That becomes more critical in patients who have prior PV [polycythemia vera] or ET [essential thrombocythemia].

Because the progression can be insidious unless you’re totally on top of it, it’s important to look at the whole leukoerythroblastic picture if you’re familiar with the diagnosis of post-ET or post-PV MF, the development of anemia, leukoerythroblastosis, new splenomegaly, etc. You look at the constitutional symptoms and whether your patient with PV isn’t requiring phlebotomy and developing anemia when they shouldn’t, then perhaps you do a bone marrow biopsy. In someone who may have thrombocytosis without an explanation, you’d need to do bone marrow biopsy to make that diagnosis.

Essentially, that’s what should be done to make this diagnosis. Then it’s important to obtain all additional genetic testing that’s included in the cytogenetics when the diagnosis is made. But there’s a problem with that, because sometimes those patients can be a dry tap and you might not be able to obtain genetic tests or genetics. I typically get them from the peripheral blood, but I’m curious to see what you do. Next-generation sequencing has become so important for risk stratification and to determine what to do in terms of stem cell transplant, which continues to be the only curative treatment for this subset of patients. Granted, assessment of symptoms is so important in this patient population. It should be done at baseline and as we move forward with various treatments we employ.

Rami Komrokji, MD: I agree. We now know more about the phenotypes of myelofibrosis: cytopenic vs proliferative. The patient presentation with myelofibrosis is either those who have cytopenia predominantly up front or proliferative with splenomegaly constitutional symptoms. I always like to point out that not every fibrosis you see in the bone marrow is myelofibrosis. That can be seen with diseases that mimic myelofibrosis, like myelodysplastic syndrome. I’ve had several cases where it was marginal zone lymphoma or hairy cell leukemia. Not every fibrosis in the bone marrow is myelofibrosis.

On the other hand, you don’t always need to see fibrosis to establish the diagnosis of myelofibrosis, because now we talk about this prefibrotic myelofibrosis entity, where the classical megakaryocytic clustering that we see in MPN is enough to make the diagnosis. They don’t have to have the +2, +3, but it’s key. A lot of those patients will have evidence of a clonal marker. Almost 90% will have either JAK2, MPL, or calreticulin. I always go extensively more than if they were triple negative to make sure we’re labeling this the right way. To your point, we do most of the next-generation sequencing on peripheral blood in those patients. The concordance is pretty good and high. As you mentioned, many times with the bone marrow, it’s a dry tap.

Transcript edited for clarity.

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By Andrea S. Blevins Primeau, PhD, MBA
Hematology Advisor

Vaccination for SARS-CoV-2 infection reduced the risk of COVID-19 mortality and hospitalization in patients with myeloproliferative neoplasms (MPNs), according to the results of a study that was presented at the EHA 2022 Hybrid Congress.

Prior to this study, there were “no robust data on characterizing the clinical outcomes of patients with MPN and COVID-19 in the United States,” the authors reported.

The single-center, retrospective, observational cohort study evaluated data from 388 patients with MPN and COVID-19 between April 2020 and December 2021. Of these patients, 53 had positive SARS-CoV-2 test results by RT-PCR.

“To date, this is the largest cohort of MPN patients with COVID-19 infection in the US, which accounts for 14% of the MPN patients in our center,” the authors reported.

The median age at baseline was 59 years, 51% of patients were men, and 46% had a body mass index (BMI) of 30 kg/m² or higher. The cohort comprised 55% of patients with myelofibrosis (MF), 28% with polycythemia vera (PV), and 17% with essential thrombocythemia (ET). The most common comorbidities were hypertension, present in 60% of patients, and diabetes, which was present in 19%.

Hospitalization was required for 47% of patients; of these patients, 68% required supplemental oxygen. Patients with MF had the highest rates of hospitalization, at 68%, compared with patients with PV or ET. The median length of stay was 8 days.

There were 49% of patients who had been vaccinated. Infection after the first dose of the vaccine occurred in 23% of patients.

Vaccination against SARS-CoV-2 was associated with better outcomes. Hospitalization rates were lower among patients who were immunized, at 28%, compared with 72% for patients who were not immunized.

Of the 9 patients who died, all but 1 were unvaccinated. The median overall survival of vaccinated patients was not reached, compared with 19.9 months among patients who were unvaccinated.

Overall, the case fatality rate of SARS-CoV-2 infection was 17%. The median overall survival was not reached during a median follow-up of 14.8 months.

The authors concluded that SARS-CoV-2 vaccination significantly decreases the risk of mortality and hospitalization in patients with MPN. In addition, they added that BMI 30 kg/m² or higher appears to be an important risk factor.

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Authors: Paulina Galka-Marciniak, Zuzanna Kanduła, Adrian Tire, Wladyslaw Wegorek, Kinga Gwozdz-Bak, Luiza Handschuh, Maciej Giefing, Krzysztof Lewandowski & Piotr Kozlowski

Abstract

Aaron T. Gerds, MD, MS, spoke with Healio about the REVEAL study, results of which were presented at this year’s European Hematology Association Congress.

REVEAL is the largest prospective, observational study of patients with polycythemia vera ever completed.

Researchers aimed to collect data on disease burden, clinical management and patient-reported outcomes of more than 2,500 adults with polycythemia vera.

The analysis presented at EHA showed elevated hematocrit levels, white blood cell counts and platelet counts influenced thromboembolism risk in this patient population.

In this video, Gerds — associate professor of medicine at Cleveland Clinic Taussig Cancer institute — provides an overview of the study findings and their potential implications.

“This represents a very ripe database that will most certainly pay off for years in the future as we go through several iterations of analysis,” Gerds told Healio.

Read more and watch the video

Reference:

Gerds AT, et al. Abstract P1062. Presented at: European Hematology Association Congress; June 9-12, 2022; Vienna.

Abstract

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The PAN Foundation today announced an expansion of its transportation fund, providing up to $500 per year to help eligible patients access affordable and reliable transportation to services and activities that improve their overall health outcomes.

PAN’s transportation program, which first launched in 2020, addresses socioeconomic barriers to medical care and medication adherence. A survey of PAN patients in 2021 showed that after receiving a transportation grant, medication adherence increased by 52 percent and adherence to physician visits increased by 29 percent.

Under the expanded program, patients will be able to use their grants to pay for transportation to access healthcare services, get social support, and even travel to the grocery store.

Expanding the program and covered services will better serve the holistic needs of each patient. Improving access to transportation removes barriers to medical care, reduces social isolation, and decreases risks for food insecurity, particularly for older adults and people living with serious illnesses.

“Since its inception, PAN’s transportation fund has led to better health outcomes for thousands of patients who needed help getting to their medical care,” said PAN President Kevin L. Hagan. “We know this expansion will help even more patients, who will now be able to use funding to better access social support and healthy food. We are grateful for the continued support of our generous donors, who enabled the expansion of this program that will reduce health barriers and improve lives.”

Patients who qualify are eligible to receive $500 per year in financial assistance in the form of a prepaid debit card, which is authorized for eligible expenses.

Eligibility requirements

To get financial assistance for transportation, patients must:

• Be currently enrolled in a co-pay or premium disease fund at the PAN Foundation and receiving treatment for that disease.
• Reside and receive treatment in the United States or U.S. territories. (U.S. citizenship is not a requirement.)

• Have health insurance that covers the qualifying medication or product.
• Have an income that falls at or below 500 percent of the federal poverty level.

How to apply

Patients or caregivers applying on their behalf can apply for assistance using the PAN Foundation’s online patient portal. A series of how-to guides are also available for the patient portal, including common tasks like creating an account and applying for assistance online.

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