Hi, my name is Karolina Faysman. I'm an advanced oncology certified nurse practitioner at the Ronald Reagan UCLA Medical Center and Santa Monica UCLA Medical Center.

Today, I’m going to discuss my management approach for patients with chronic GVHD and cytopenias.

Overall, cytopenias do not prevent me from considering Jakafi for my patients with chronic GVHD.

When we consider management approaches for cytopenia, it is crucial to differentiate whether the patient is presenting with a disease- versus drug-related cytopenia.

In my practice, a majority of patients present with immune-mediated pancytopenia due to GVHD. Measurements of antineutrophil antibodies are important to identify that. If cytopenias are disease-mediated, Jakafi is still my agent of choice for appropriate patients with platelet counts 20,000 and above, at the first sign of initial systemic treatment failure.

Too many times, I have seen providers assuming that cytopenias are Jakafi-related without further investigation and instituting dose modifications when not appropriate.

Once we rule out immune-mediated cytopenias, we know they are drug-related, and the type and level of cytopenia will guide our next steps for therapy.

I have confidence in managing anemia, thrombocytopenia, and neutropenia, from my clinical experience and the REACH3 trial data.

REACH3 is a randomized, open-label, multicenter, phase 3 study of Jakafi vs best available therapy, or BAT, in patients with steroid-refractory chronic GVHD.

In the REACH3 trial, anemia and thrombocytopenia were the most common adverse events associated with Jakafi.

Overall, treatment discontinuation due to adverse events occurred in 16% of patients receiving Jakafi and 7% receiving BAT.

When it comes to cytopenias, 1 patient in each arm discontinued treatment due to anemia, 1 patient on Jakafi and 2 on BAT discontinued due to neutropenia, while no patients receiving Jakafi were discontinued due to thrombocytopenia.

Despite dose modifications due to cytopenia, patients had a median dose intensity of 19.6 mg of Jakafi per day at week 24, which is close to the maximal dose of 10 mg twice daily on Jakafi.

As seen on screen, clinically meaningful differences in platelet and neutrophil counts between the Jakafi arm and BAT were not observed over time. These data from REACH3 is consistent with what I see in my clinical practice, where counts may drop initially but, in general, they stabilize.

So, what would be the appropriate course of action if our patients developed cytopenia while on Jakafi?

If platelet count is less than 20,000, reduce Jakafi by 1 dose level. If resolved within 7 days, dosing may return to the initial dose level. If not resolved within 7 days, then maintain at 1 dose level lower.

If absolute neutrophil count, or ANC, is less than 750 and considered related to Jakafi, you may reduce Jakafi by 1 dose level and return to initial dose level upon ANC recovery.

If ANC is less than 500 and considered related to Jakafi, then you may need to hold Jakafi for 14 days and resume at a lower dose upon recovery and resume initial dose when ANC level is greater than 1000.

When it comes to cytopenias, my preference is to reduce the dose when possible and avoid withholding Jakafi. It is very important to me that the patient has continuous exposure to Jakafi to potentially control their disease.

In summary, I am comfortable treating patients with Jakafi who have cytopenias. For these patients, it is important to first differentiate whether the cytopenias are disease-related or Jakafi-related and intervene. This may include adjusting the dose of Jakafi and avoiding premature discontinuation in appropriate patients. This would allow us to potentially maintain control of the disease and prevent progression.

Thank you for listening.

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

INDICATIONS AND USAGE

Jakafi^® (ruxolitinib) is indicated for treatment of chronic graft-versus-host disease (cGVHD) after failure of one or two lines of systemic therapy in adult and pediatric patients 12 years and older.

IMPORTANT SAFETY INFORMATION

• Treatment with Jakafi 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.