Dr Rampal: “Hello and welcome. I’m Dr Raajit Rampal. Today, I am excited to share findings from a recent MPN practice perspectives survey focusing on optimizing the management of patients with polycythemia vera. Joining me in my review is fellow MPN expert Dr Prithviraj Bose.”

Dr Bose: “Thanks, Dr Rampal, I am excited to discuss the results of this survey with you.”

Dr Rampal: “Well, before we get started, let’s discuss the objectives. With this survey, we wanted to gain real-world perspectives on the management of patients with PV. And so, 
for PV, the focus of the survey was on the management of thrombosis and the importance of monitoring blood counts to reduce the risk of thrombosis. The primary objective of the survey was to ensure that we optimize the way we manage patients with PV and of course address educational gaps.”

Dr Rampal: “So, as we get into thinking about the pathology of PV, we understand that thrombosis is the most serious problem we face. Reducing the risk of thrombosis is our number one treatment goal for these patients because cardiovascular-related events represent one of the most common causes of mortality in PV. Ensuring that we are monitoring and optimizing treatment for these patients is extremely important.”

Dr Bose: “That is a great point and something we all need to consider for patients with PV, especially because many times the care of these patients is put on autopilot. So I think the survey and your perspectives will be important for us to understand. With that being said, the first question that physicians were asked within the survey was, ‘Which blood counts are you most concerned about when managing your patients for the risk of thrombosis?’”

Dr Rampal: “Yes, and this is an important point because, as you see here, almost everyone monitors hematocrit—which is great, but what is surprising to me is that about a third of HCPs did not mention white blood cell count. And as you know it’s surprising, because when it comes to white blood cell counts, we have to understand that there is mounting evidence that has demonstrated that an increase in the white blood cell count can lead to an increase in the risk of thrombotic events—and again, decreasing that risk is our primary treatment goal. So it’s critical for us as physicians to monitor white blood cell counts. And, of course, this is supported by the NCCN Guidelines, which recognize that leukocytosis is an important factor indicating whether to implement cytoreductive therapy in low-risk PV patients or to change cytoreductive therapy in high-risk PV patients.”

Dr Bose: “You’re exactly right, and I think this is where the CYTO-PV study is important for us to discuss. But before we go there, the second question that physicians were asked in the survey was ‘What is the maximum white blood cell count you would allow when managing patients with PV for the risk of thrombosis?’ Let’s chat a little bit about those results.”

Dr Rampal: “Absolutely, so, as I was reviewing these results, it was great to see that 39% of respondents said that would they try to keep the white blood cell count to less than 11, because of course that aligns with the findings of the CYTO-PV study. And in the subanalysis of that study they found that there was an increased risk in the risk of thrombosis among patients with a white blood cell count higher than 11. On the other hand, 61% stated that they either do not manage white blood cell count for the risk of thrombosis or, in fact, are comfortable if white count exceeds 11. That’s concerning to me because the number one treatment goal here, of course, is to reduce the risk of thrombosis.” 

“And the key takeaway is that if white blood cell counts should be looked at as an independent risk factor for thrombosis. And for me, if I see a progressive increase in the white blood cell count above 11, I will re-evaluate my management approach.”

Dr Bose: “I couldn’t agree more, and this is where understanding the risks associated with leukocytosis is extremely important when managing these patients for thrombotic risk. Along with white blood cell count control, we can’t forget the importance of strict hematocrit control. As we move along in this survey, the next question asked was ‘What is your target hematocrit level when managing patients for the risk of thrombosis?’ What are your thoughts on the results of this question?”

Dr Rampal: “So, overall, the majority of HCPs said that they target a hematocrit of 45%.”

Dr Bose: “Which is great, but I’m curious on your perspectives around the final question of the survey, where participants were asked, ‘What is the maximum hematocrit level you would allow before considering a change in management approach for patients on a maximum tolerated dose of hydroxyurea?’”

Dr Rampal: “Well, I think that although the majority target 45%, you can see here approximately 80% of our colleagues state that they do not do anything differently if the hematocrit is higher than 45%—meaning that they’re comfortable allowing the hematocrit to be a few points above 45%. That’s concerning to me because when we look at the data from the CYTO-PV study, they clearly demonstrate in that study a 4-fold higher risk of major thrombosis when the hematocrit is between 45% and 50%. That's why I ensure in my practice that my patients who have an established dose of hydroxyurea have a hematocrit of less than 45% at all times.”

“Another thing to consider is the use of phlebotomy with cytoreductive therapy. While this is an evolving discussion, if a patient is on an intermediate or high dose of hydroxyurea and is at the point where they’re receiving 4 phlebotomies a year, I think it’s reasonable to rethink the strategy and consider a change in treatment. Overuse of phlebotomy can result in a number of sequelae, as you know, including iron deficiency and pulmonary hypertension, among other issues.”

“The evidence for risk of thrombosis is established. The time to intervene is at 45% or lower, depending on the individual. Even 45.1% has exceeded the threshold. Each time a patient requires a phlebotomy or an adjustment in the hydroxyurea dosage, they face a period of increased vulnerability to thrombotic events. We don’t want to look back on the management of any individual who may have experienced a thrombotic event and wish that we had taken a more active approach.”

Dr Bose: “I think this is important for all of us to remember, and this is a message I myself have strongly conveyed in the past. I firmly believe that it cannot be stressed enough as we manage these patients for the risk of thrombosis.”

“Once again, Dr Rampal, I appreciate your insights and hope that our colleagues find this discussion educational and informative in regard to their practice and the management of their patients with PV. Do you have any closing thoughts or advice?” 

Dr Rampal: “Well, first of all, thank you, Dr Bose. I’d also like to say thank you to those who took time to participate in the survey. I enjoyed reviewing the results and providing my perspectives. I understand many of you are seeing several patients a day across a broad spectrum of oncology, and patients with PV may be rare. And I hope you’ll find this to be beneficial. And in closing I just want to say: When it comes to managing patients with PV for the risk of thrombosis, we should implement an evidence-based management strategy for every patient and not leave any factors to chance. Especially when it comes to managing white blood cell counts to less than 11 and strict hematocrit control less than 45% to attenuate the risk of thrombosis.”

Dr Bose: “Thanks for watching. I hope you have a chance to tune in to our discussion regarding the importance of optimizing the management of patients with myelofibrosis.”

Dr Bose: “Hello and welcome. I’m Dr Prithviraj Bose. Today, I’m excited to share findings from a recent survey called the MPN Practice Perspectives Survey. The focus of this survey was on the importance of managing patients with myelofibrosis early in the course of their disease for overall survival benefit. And joining me today in this discussion is fellow MPN expert Dr Raajit Rampal.”

Dr Rampal: “Thanks, Dr Bose. I’m happy to be here and very excited for this discussion.”

Dr Bose: “So let’s begin with the key objectives of this survey, which included understanding real-world perspectives when it comes to the management of patients with MF. We wanted to understand what the treatment goals were, how healthcare providers were prioritizing overall survival for these patients, how patients were managed upon diagnosis, and how cytopenias were being managed.”

Dr Rampal: “So these are all really relevant topics you brought up, and it’s going to be very interesting to see the results of this survey. So let’s get right into it!”

“The survey opened up by asking healthcare professionals, ‘What is your primary treatment goal when treating your patients with MF?’ So what do the results look like?”

Dr Bose: “Well, you can see here that 43% of healthcare providers said reduction in spleen volume and total symptom score were their primary goals, which is great to see. However, only 38% said overall survival is a treatment goal. This was interesting because as we think about MF and the evolving treatment landscape, we have many more treatment options today than we had 10 years ago. There is evidence that demonstrates a correlation between intervening early and overall survival. Given this, overall survival should be the primary treatment goal for these patients! I know in my practice it is my primary treatment goal.”

Dr Rampal: “I couldn’t agree more on this. In my practice, I do actively manage patients with MF at diagnosis because the majority of them have symptoms, and this is in line with NCCN recommendations. The idea here, I think, is to manage them early—instead of watching and waiting—to maximize the benefit of the treatments that we have.”

“I also see that 19% selected cytopenias as a treatment goal, which is a little surprising. Cytopenias are something that we’ve always managed, and that we need to continue to manage, but I’ve never considered it a treatment goal. What’s your perspective on this?”

Dr Bose: “I’m with you on this. As I think about treatment goals, I want to ensure that if my patient is not a candidate for transplant, I am maximizing my treatment options for overall survival along with spleen volume reduction and improvement of symptoms. As for cytopenias, I manage them as needed to achieve my 3 treatment goals. With that said, I’ve also noticed that when these patients are diagnosed, about 90% are candidates for active treatment. So rather than watch and wait, it's best to start treatment earlier in the course of the disease when blood counts are pretty manageable. This approach allows us to maximize our treatment options for overall survival.”

“And on the topic of cytopenias being a goal or not being a goal for the treatment of MF, I do want to note that physicians who said that it was a goal are not necessarily wrong. Because there are patients who may have anemia and/or thrombocytopenia without splenomegaly or symptoms. But this is uncommon. However, if you do come across such a patient, you certainly do want to manage their cytopenia.”

Dr Rampal: “Now you just mentioned that 90% of patients are eligible for active treatment upon diagnosis, and much of that is because 90% have a palpable spleen at diagnosis.”

“The next question asked in the survey was, 'At what baseline spleen size do you typically consider initiating treatment for a patient with MF who presents with mild to moderate symptoms?'"

“Let’s review those results.”

Dr Bose: “Well, as you can see, 42% of healthcare professionals said they would initiate treatment for patients who had a spleen between 5 and 10 cm. This makes sense because if we think about the IWG-MRT and the ELN criteria, one of the required criteria for spleen response is a palpable baseline spleen of 5 to 10 cm (below the left costal margin) that then has to become nonpalpable for 12 weeks or more. However, what concerns me a bit is that a third of HCPs said they would wait until the spleen was greater than 10 cm below the left costal margin.”

“This is concerning because there is clear data that demonstrates that a larger baseline spleen volume is associated with an incremental increase in the risk of death. To be specific, for every 5 dL increase in spleen volume, there is a 14% increase in the risk of death. So based on this, I would encourage healthcare professionals to not watch and wait, but rather initiate active treatment to reduce the spleen size.”

Dr Rampal: “So that’s a really important point that you make. Watching and waiting, or even using hydroxyurea, which we see now and again, should not be the way we manage patients in 2024 and beyond. The treatment landscape has evolved, and we’ve got to align our management approach to maximize the overall survival benefit for our patients.”

“So the next question that was asked of healthcare practitioners was how they would typically manage patients with intermediate–1-risk MF earlier in the course of their disease. It looks like about half said they would initiate treatment with ruxolitinib; however, the other half said that they would either watch or wait or initiate hydroxyurea. So what are your thoughts on these results?”

Shown on screen:
Ruxolitinib is indicated for treatment of intermediate or high-risk myelofibrosis (MF), including primary MF, post–polycythemia vera MF and post–essential thrombocythemia MF in adults.

Ruxolitinib is available in 5-mg, 10-mg, 15-mg, 20-mg, and 25-mg tablets.

Please see Important Safety Information later in this video. Please view Full Prescribing Information for Jakafi at: https://www.jakafi.com/pdf/prescribing-information.pdf

Dr Bose: “I was a bit surprised to see so many physicians choose to watch and wait or to initiate hydroxyurea. There’s clear data that demonstrates benefits of initiating treatment earlier on in the course of the disease. And in my own practice and based on real-world experience, patients who are earlier on in the course of their disease have fewer cytopenias, smaller spleens, less genomic complexity, and a higher chance of spleen volume reduction. So, at this point, like you said, in 2024, watch and wait is not a strategy I would implement for these patients.”

Dr Rampal: “I couldn’t agree more. You mentioned there being fewer cytopenias, so let’s shift our discussion here and talk about the management approaches for patients with MF who present with anemia, as this has been a topic of some interest lately.”

Dr Bose: “Great! This was actually the last question asked in the survey, and you can see here that about half of the respondents said they were concerned when it came to the use of ruxolitinib for appropriate patients if the hemoglobin were 8 g/dL or less, or even 8 to 10 g/dL or for those requiring transfusions.”

“You know, I’m with the 50% who said nothing absolutely precludes them from using ruxolitinib for appropriate patients as this approach aligns with my clinical practice and is supported by data demonstrating the benefits of early treatment for MF patients, including those with anemia. Anemia has been a topic of concern lately, but cytopenias have been something we have always managed to achieve our long-term treatment goals. The presence of anemia does not preclude me from initiating ruxolitinib, as we can effectively apply dosing strategies tailored to these patients. Now of course, there are other treatment options that may be considered if a patient is transfusion dependent or has severe anemia with hemoglobin <8 [g/dL], but typically we reserve these options for second- or later lines following the treatment with ruxolinitib.”

Dr Rampal: "Thank you, Dr. Bose. I appreciate your insights and hope that our viewers find this discussion informative and actionable. Do you have any final thoughts to share?”

Dr Bose: “It was my pleasure. First, I’d like to say thanks to all those who took the time to complete the survey. I enjoyed reviewing the results and providing my perspectives. I understand many of you see a broad spectrum of oncology patients each day, so the time dedicated to these discussions is much appreciated. Seeing practice perspectives from diverse clinical settings helps to inform best practices. Last, I’ll say that when it comes to MF, every action or inaction today can impact long-term outcomes. We must lean on the growing body of evidence that supports initiating treatment early for appropriate patients with MF to potentially extend overall survival instead of watching and waiting.”

Dr Rampal: “Well, thanks for viewing this video on myelofibrosis. In addition, I hope you have a chance to tune in to our other discussion regarding the importance of optimizing the management of patients with polycythemia vera for the risk of thrombosis.”

INDICATIONS AND USAGE

Jakafi is indicated for treatment of intermediate or high-risk myelofibrosis (MF), including primary MF, post–polycythemia vera MF and post–essential thrombocythemia MF in adults.

IMPORTANT SAFETY INFORMATION

• Treatment with Jakafi® (ruxolitinib) can cause thrombocytopenia, anemia and neutropenia, which are each dose-related effects. Perform a pre-treatment complete blood count (CBC) and monitor CBCs every 2 to 4 weeks until doses are stabilized, and then as clinically indicated
• Manage thrombocytopenia by reducing the dose or temporarily interrupting Jakafi. Platelet transfusions may be necessary
• Patients developing anemia may require blood transfusions and/or dose modifications of Jakafi
• Severe neutropenia (ANC <0.5 × 109/L) was generally reversible by withholding Jakafi until recovery
• Serious bacterial, mycobacterial, fungal and viral infections have occurred. Delay starting Jakafi until active serious infections have resolved. Observe patients receiving Jakafi for signs and symptoms of infection and manage promptly. Use active surveillance and prophylactic antibiotics according to clinical guidelines
• Tuberculosis (TB) infection has been reported. Observe patients taking Jakafi for signs and symptoms of active TB and manage promptly. Prior to initiating Jakafi, evaluate patients for TB risk factors and test those at higher risk for latent infection. Consult a physician with expertise in the treatment of TB before starting Jakafi in patients with evidence of active or latent TB. Continuation of Jakafi during treatment of active TB should be based on the overall risk-benefit determination
• Progressive multifocal leukoencephalopathy (PML) has occurred with Jakafi treatment. If PML is suspected, stop Jakafi and evaluate
• Herpes zoster infection has been reported in patients receiving Jakafi. Advise patients about early signs and symptoms of herpes zoster and to seek early treatment. Herpes simplex virus reactivation and/or dissemination has been reported in patients receiving Jakafi. Monitor patients for the development of herpes simplex infections. If a patient develops evidence of dissemination of herpes simplex, consider interrupting treatment with Jakafi; patients should be promptly treated and monitored according to clinical guidelines
• Increases in hepatitis B viral load with or without associated elevations in alanine aminotransferase and aspartate aminotransferase have been reported in patients with chronic hepatitis B virus (HBV) infections. Monitor and treat patients with chronic HBV infection according to clinical guidelines
• When discontinuing Jakafi, myeloproliferative neoplasm-related symptoms may return within one week. After discontinuation, some patients with myelofibrosis have experienced fever, respiratory distress, hypotension, DIC, or multi-organ failure. If any of these occur after discontinuation or while tapering Jakafi, evaluate and treat any intercurrent illness and consider restarting or increasing the dose of Jakafi. Instruct patients not to interrupt or discontinue Jakafi without consulting their physician. When discontinuing or interrupting Jakafi for reasons other than thrombocytopenia or neutropenia, consider gradual tapering rather than abrupt discontinuation 
• Non-melanoma skin cancers (NMSC) including basal cell, squamous cell, and Merkel cell carcinoma have occurred. Perform periodic skin examinations
• Treatment with Jakafi has been associated with increases in total cholesterol, low-density lipoprotein cholesterol, and triglycerides. Assess lipid parameters 8-12 weeks after initiating Jakafi. Monitor and treat according to clinical guidelines for the management of hyperlipidemia
• Another JAK-inhibitor has increased the risk of major adverse cardiovascular events (MACE), including cardiovascular death, myocardial infarction, and stroke (compared to those treated with tumor TNF blockers) in patients with rheumatoid arthritis, a condition for which Jakafi is not indicated. Consider the benefits and risks for the individual patient prior to initiating or continuing therapy with Jakafi particularly in patients who are current or past smokers and patients with other cardiovascular risk factors. Patients should be informed about the symptoms of serious cardiovascular events and the steps to take if they occur
• Another JAK-inhibitor has increased the risk of thrombosis, including deep venous thrombosis (DVT), pulmonary embolism (PE), and arterial thrombosis (compared to those treated with TNF blockers) in patients with rheumatoid arthritis, a condition for which Jakafi is not indicated. In patients with myelofibrosis (MF) and polycythemia vera (PV) treated with Jakafi in clinical trials, the rates of thromboembolic events were similar in Jakafi and control treated patients. Patients with symptoms of thrombosis should be promptly evaluated and treated appropriately
• Another JAK-inhibitor has increased the risk of lymphoma and other malignancies excluding NMSC (compared to those treated with TNF blockers) in patients with rheumatoid arthritis, a condition for which Jakafi is not indicated. Patients who are current or past smokers are at additional increased risk. Consider the benefits and risks for the individual patient prior to initiating or continuing therapy with Jakafi, particularly in patients with a known secondary malignancy (other than a successfully treated NMSC), patients who develop a malignancy, and patients who are current or past smokers
• In myelofibrosis and polycythemia vera, the most common nonhematologic adverse reactions (incidence ≥15%) were bruising, dizziness, headache, and diarrhea. In acute graft-versus-host disease, the most common nonhematologic adverse reactions (incidence >50%) were infections (pathogen not specified) and edema. In chronic graft-versus-host disease, the most common nonhematologic adverse reactions (incidence >20%) were infections (pathogen not specified) and viral infections 
• Avoid concomitant use with fluconazole doses greater than 200 mg. Dose modifications may be required when administering Jakafi with fluconazole doses of 200 mg or less, or with strong CYP3A4 inhibitors, or in patients with renal or hepatic impairment. Patients should be closely monitored and the dose titrated based on safety and efficacy 
• Use of Jakafi during pregnancy is not recommended and should only be used if the potential benefit justifies the potential risk to the fetus. Women taking Jakafi should not breastfeed during treatment and for 2 weeks after the final dose 

Please view Full Prescribing Information for Jakafi at: https://www.jakafi.com/pdf/prescribing-information.pdf