Hi, my name is Salman Fazal and I am a hematologist and a bone marrow transplant physician at Allegheny Health Network. Let’s talk about how I manage my myelofibrosis patients who have disease-related anemia or may develop treatment-related anemia while taking Jakafi.

First and foremost, myelofibrosis is a serious disease that I believe requires active management at diagnosis. Therefore, when I have a patient who presents with anemia, it is not a reason for me to delay treatment with Jakafi.

I’m often asked, “is there a hemoglobin level that I’m concerned about when initiating Jakafi in an appropriate patient with myelofibrosis?” And my answer is always “no”. Anemia is not a contraindication for Jakafi and it should not be a barrier for initiating treatment.

In patients with myelofibrosis who are anemic at diagnosis, I first educate the patients that there may be an additional drop in hemoglobin around 8 to 12 weeks when on Jakafi. And if it does occur, we will not stop treatment. This is because, as demonstrated in COMFORT trials, we will be able to manage through the anemia utilizing red blood cell transfusion when appropriate.

I let them know that I believe the benefits of Jakafi outweigh the upfront concerns of anemia.

I initiate Jakafi at diagnosis because we know it is effective at reducing spleen volume and symptoms, which is my primary focus when managing my intermediate to high-risk myelofibrosis patients regardless of anemia status.

This was clearly demonstrated in the COMFORT-I study as well, which was a phase III trial that enrolled patients with intermediate-2 to high-risk myelofibrosis. The study was designed to look at the spleen volume reduction of at least 35% at week 24, which investigators assessed using CT or MRI.

In this study, they assessed patients receiving Jakafi compared with placebo. And it is also important to note that in the COMFORT-I study, 46% of patients receiving Jakafi had a baseline anemia with a mean hemoglobin of 9.2 grams per deciliter and a range of 6.6 to 13.7 grams per deciliter, which is consistent with what I see in my patients with myelofibrosis in practice.

The study demonstrated that significantly more patients receiving Jakafi, approximately about 42% of patients, achieved greater than or equal to 35% of reduction in their spleen volume versus less than 1% receiving placebo.

While patients with baseline anemia were included in the trial, it was also interesting to see that once on Jakafi, patients with new onset grade 3 or 4 anemia had comparable efficacy to patients without anemia.

And for symptom improvement, we saw the same thing: 46% of patients on Jakafi achieved greater than or equal to 50% improvement in total symptom score at week 24 versus 5% for patients receiving placebo and there was no clinically meaningful difference in symptom improvement, whether there was new onset grade 3 or 4 anemia or not.

When managing patients on Jakafi, it is important to note in the COMFORT-I study, there was a mean decrease in the hemoglobin level, which reached a nadir of approximately 1.5 to 2 grams per deciliter below baseline in the first 8 to 12 weeks of therapy.

However, the hemoglobin did gradually recover to reach a new steady state that was approximately 1 gram per deciliter below baseline.

And 60% of patients also required RBC transfusion, but that requirement decreased over time. Finally, it is also important to note that while 96% of patients receiving Jakafi in the COMFORT trials experienced anemia, less than 1% of patients discontinued therapy due to anemia.

This tells me, anemia can be manageable and if I want to achieve improvement in symptoms and spleen volume, I should be able to manage through these potential issues.

These results help give me the confidence to initiate Jakafi at diagnosis in my appropriate patients with myelofibrosis, regardless of their hemoglobin level and the confidence to manage new onset anemia if it should occur while my patients are on Jakafi.

Let’s take the opportunity to review the safety information for Jakafi.

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.