Jakafi (ruxolitinib) is indicated for treatment of steroid-refractory acute graft-versus-host disease (GVHD) in adult and pediatric patients 12 years and older. 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. Additional Important Safety Information is discussed within this video.
Hi, I’m Dr Pashna Munshi, a bone marrow transplant physician from the Washington DC area. I would like to share some information with you about a serious disease called acute GVHD that may progress rapidly in some patients. This promotional presentation is being sponsored by Incyte Corporation. The speaker is presenting on behalf of, and is being compensated by, Incyte Corporation.
GVHD is a potentially life-threatening complication of allogeneic hematopoietic stem cell transplantation. It can present as an acute or chronic disease, each with a distinct pathophysiology and presentation.
Let’s focus on acute GVHD and timing. While it can occur at any time, acute GVHD typically occurs in the first few months after transplant.
The first-line standard of care in acute GVHD is treatment with steroids. But, even within the first few days of treatment, patients with acute GVHD may not respond to steroid treatment and may require additional therapy. Criteria for identifying these steroid-refractory patients include progressive disease within 3 to 5 days, failure to improve within 5 to 7 days, or incomplete response after more than 28 days of treatment including steroids.
Steroid-refractory acute GVHD is not uncommon. We know that approximately 50 percent of patients will require additional therapy, either because they have an incomplete initial response or because they cannot have their steroid dose tapered without flare. With regards to outcomes, in each of two studies that directly compared outcomes in steroid-refractory and steroid-dependent populations, both populations had similarly poor outcomes. Because of this, assessing your patients and their response to steroids in a timely manner is critical.
Let’s look at the risk of progression in patients with acute GVHD. In an Incyte-sponsored, multicenter, retrospective chart review conducted in 168 patients with steroid-refractory Grade II to IV acute GVHD, 54 percent of patients had new organ involvement or an increase in acute GVHD grade. In the same study, 40 percent of patients with Grades II or III disease advanced to a higher maximum grade. In fact, median time from acute GVHD diagnosis to maximum grade was 6 days, which speaks to the potential for rapid progression within this disease.
Remember that steroid-refractory patients can be identified early, as early as three days from the start of treatment. Because you can identify steroid-refractory acute GVHD early, and because of the risk of progression of acute GVHD, early identification and timely action are critical. I would suggest considering Jakafi at the first sign of steroid-refractory acute GVHD.
We’ll now turn to safety information about Jakafi.
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.
Thanks for watching. You can learn more about Jakafi for patients with steroid-refractory acute GVHD by visiting hcp.jakafi.com.