Hi, my name is Salman Fazal and I am a hematologist and a bone marrow transplant physician at Allegheny Health Network.

Today, I would like to talk about how Jakafi spleen and overall survival data gives me the confidence to start treatment early in the course of the disease for my appropriate patients with myelofibrosis, instead of watching and waiting or initiating hydroxyurea.

I believe overall survival is a very important topic because our patients ask us about it. In my practice, I align my goals with the patient. I want to understand what is most important to them. And many times, it is about making sure they’re able to continue their activities of daily living to the best of their ability.

First and foremost, myelofibrosis is a serious disease that I believe requires active management at diagnosis. Therefore, I do not delay treatment. And we also know that new or increasing splenomegaly is a sign of disease progression.

And based on my experience, approximately 90% of my patients have a palpable spleen at diagnosis which aligns to what we see in literature as well. And if myelofibrosis patients have progressive splenomegaly, and treatment is delayed, those patients may not do well. So, for most of my appropriate patients with myelofibrosis who have splenomegaly at diagnosis, which 90% do, I intervene with Jakafi. We know from the COMFORT studies that Jakafi is effective at reducing splenomegaly related to myelofibrosis.

And we also saw overall survival data as a secondary endpoint in those studies. COMFORT-I, a phase 3 trial that enrolled patients with intermediate-2 or high-risk myelofibrosis was designed to look at spleen volume reduction of at least 35% at week 24, which investigators assessed using CT or MRI. They assessed patients receiving Jakafi versus placebo.

The study found that significantly more patients on Jakafi achieved a spleen volume reduction than patients receiving placebo.

COMFORT-II was another phase 3 trial that enrolled patients with intermediate-2 or high-risk myelofibrosis and was also designed to look at spleen volume reduction of at least 35% at week 48 assessed by CT or MRI. In this study, investigators assessed patient receiving Jakafi versus best available therapy or BAT, 47% of whom received hydroxyurea.

They found that more patients on Jakafi achieved greater than or equal to 35% spleen volume reduction at week 48 compared to 0% in the BAT group. COMFORT-II was quite similar to COMFORT-I study in terms of being a randomized trial. However, the unique aspect of COMFORT-II was the fact that the control arm was best available therapy.

When I look at the overall survival curve from the COMFORT-I study we know that all patients in the placebo group crossed over to Jakafi at a median of 9 months or discontinued therapy. So when we look at both groups, those who were initially randomized to Jakafi and then those who started placebo and then either crossed over or discontinued therapy, we can see that at three years, the survival probability was 70% for patients originally randomised to Jakafi and 61% for those originally randomised to placebo and when we look at the 5 years survival probability with Jakafi it was 51%.

The fact that we are talking about 5-year survival data is an achievement in itself. My patients frequently ask their odds of survival on Jakafi. I think the data from COMFORT studies is useful in terms of answering their question.

So when we look at both groups in COMFORT-II, those who initially randomized to Jakafi earlier and then those who started BAT and then either crossed over or discontinued therapy, we can see that in 3 years, the survival probability was 79% for patients originally randomised to Jakafi and 59% for those originally randomised to BAT. And when we look at the 5- year survival probability with Jakafi, it was 56% and for those who were initially on BAT which included hydroxyurea, the survival probability was 44%.

Given these data from COMFORT-II in my practice, this is why I do not use hydroxyurea for my myelofibrosis patients. So, the overall survival data available from COMFORT studies give me the confidence of prescribing Jakafi for my appropriate patients at diagnosis and not to delay the treatment. So, when my adult patients with intermediate to high-risk myelofibrosis is experiencing any degree of splenomegaly at diagnosis, that is a sign that I need to intervene with 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.