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

Today, I’d like to talk about when I intervene with Jakafi in my intermediate to high-risk myelofibrosis adult patients, and the importance of intervening early in the course of the disease.

I believe myelofibrosis is a serious hematological malignancy that is associated with poor survival. I do see benefit of intervening early versus delaying treatment for these patients.

Consistent with literature, I find that approximately 90% of my patients with myelofibrosis present with some degree of splenomegaly at diagnosis.

For me, it’s important to identify and manage splenomegaly early, because we know that a larger baseline spleen volume has been associated with increased risk of death.

Based on a pooled analysis of overall survival in the COMFORT studies, it has been shown that for each additional 5 deciliter in spleen volume at baseline, there was a 14% increase in the risk of death over three years.

Therefore, I start Jakafi early for appropriate patients, to not only prevent the spleen from increasing but to give it the chance of getting back to normal size.

And this benefit was demonstrated through the Jakafi clinical trials. COMFORT-I, a phase III 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.

So, in my practice, I personally intervene rather than delaying treatment. This is supported by the data from the COMFORT-I study. 42% of patients on Jakafi met the primary endpoint, meaning their spleen volumes were reduced by at least 35% at week 24. This was significantly more than patients on placebo, which was less than 1%.

And for those patients who started on Jakafi, ninety-nine percent of them experienced some reduction in spleen volume. On the flip side, if we look at the placebo arm, a majority of patients experienced an increase in spleen volume. Based on these data alone, if an appropriate patient has splenomegaly, there is no reason to wait to intervene with Jakafi.

One question I am often asked is that since the COMFORT trials included intermediate-2 or high-risk patients, and because Jakafi is approved for all intermediate risk patients, would I initiate Jakafi for my intermediate-1 risk patients, or those patients that are earlier in the course of the disease? And my answer is yes. If you have an intermediate-1 risk patient with splenomegaly and/or symptoms, Jakafi can be appropriate. Now I would like to take you through some interesting findings from the JUMP study

The JUMP study was a single arm, open label, Phase 3b expanded access study of patients with primary or secondary myelofibrosis, classified as intermediate-1, intermediate-2 or high-risk disease. The primary endpoint of the study was the assessment of Jakafi’s safety and tolerability.

In the overall JUMP population, the safety profile was generally consistent with previous reports for Jakafi. However, one thing that stood out to me was the incidence of cytopenia in intermediate-1 risk patients.

When we look at the reduction in spleen length from a full cohort perspective, 67% of those patients who were evaluable had a greater than or equal to 50% reduction from baseline in palpable spleen length at week 96.

What was interesting to me was when I look at this graph, a higher percentage of patients in the intermediate-1 risk group achieved greater than or equal to 50% reduction in the spleen compared to intermediate-2 and high-risk patients.

And although, both groups had a response, you can clearly see that at the 24-week mark, that response plateaued in the intermediate-2 and high-risk patients. But in the intermediate-1 risk population, it continued to improve over time.

Not only that, but if you look at the waterfall plot for these intermediate-1 risk patients, 99% of these patients had a spleen response.

And if you look along the y-axis, you can see that a portion of those patients had a complete resolution or almost complete resolution of palpable splenomegaly, which to me is very compelling.

Based on my clinical experience taking care of myelofibrosis patients for more than a decade, patients who have an enlarged spleen will have a different course of their disease.

Which is why we need to catch the disease early so that we can give our patients the chance of normalizing their spleen size. When we do this, patients tend to do better. So, in my practice, these data reinforce the importance of intervening early at that point of diagnosis and gives me the confidence to start Jakafi in appropriate patients.

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.