Narrator: The REACH Studies in Steroid-Refractory Acute GVHD

Part 2: Additional Data

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.

DR Bishop: Hello. I’m Dr Michael Bishop, a bone marrow transplant physician from the Chicago area. I would like to share clinical trial data with Jakafi in patients with Grade II, III or IV steroid-refractory acute GVHD.

Narrator: This promotional presentation is being sponsored by Incyte Corporation.

The speaker is presenting on behalf of, and is being compensated by, Incyte Corporation.

Dr Bishop: Approval of Jakafi for use in steroid-refractory acute GVHD was based on positive results of the open-label, single-arm phase 2 REACH1 study.

As you can see in the REACH1 study, the overall response rate was 57 percent at day 28.

The key secondary endpoint, median duration of response, was calculated using 2 methods, each with a different definition of disease progression as seen on the screen.

The most common nonhematologic adverse reactions in the REACH1 study were infections, edema, and hemorrhage.

The most common hematologic adverse events were anemia, thrombocytopenia, and neutropenia.

REACH2 was a randomized, open-label, phase 3 study conducted outside the United States across 105 treatment centers in 22 countries and includes endpoints that are not reported in the Jakafi Prescribing Information.

Some differences to note about the two studies include that REACH2 was a phase 3 study with a comparison arm of control therapy and included a total of 309 patients. Patients randomized to the control arm and meeting certain criteria could cross over to Jakafi after Day 28.

The starting dose of Jakafi in this study was 10 mg twice daily.

Control therapy was chosen by the investigator at the time of randomization.

The primary endpoint of the REACH2 study was overall response rate at Day 28.

In the REACH2 study, 62.3 percent of patients treated with Jakafi achieved complete or partial response, compared with 39.4 percent of patients treated with control therapy. This difference was statistically significant.

In this study, 55 percent of Day 28 responders, 34% of patients in the Jakafi cohort, had a complete response with Jakafi.

A subgroup analysis by grade was performed based on the overall response rate data. Improvement was observed across all grades studied in patients treated with Jakafi. The highest response rates were seen in patients with Grade II acute GVHD.

The overall response rate for patients with Grade II disease was over 75 percent with Jakafi, with over 50 percent of patients with Grade II demonstrating complete response.

Grade II patients in the control arm were also more likely to have a complete response than patients with Grade III or IV disease.

An additional subgroup analysis was performed to examine overall response rate by organ involvement at baseline. The Jakafi cohort had higher overall response rates at Day 28 vs control therapy for skin, lower and upper GI tract, and liver.

Jakafi also demonstrated a higher rate of complete response across all organs involved.

Durable overall response rate at Day 56 was a key secondary endpoint in the REACH2 study.

In REACH2, in patients treated with Jakafi, the durable response rate was 39.6%. In patients treated with control therapy, the durable response rate was 21.9 percent.

Of note, 21 percent of patients treated with Jakafi were able to discontinue steroids by Day 56, compared with 14 percent of patients receiving control therapy.

In the REACH2 study, several secondary endpoints were analyzed without control for multiple testing. Failure-free survival was one of these endpoints, and patients treated with Jakafi had longer median failure-free survival, or FFS, compared with those treated with control therapy.

While not a statistically significant endpoint, there was a 54 percent estimated reduction in FFS events with Jakafi compared with control therapy.

In this analysis, median FFS in patients treated with Jakafi was 5 months compared with 1 month in patients treated with control therapy.

In REACH2, the most common adverse reactions occurring in patients were thrombocytopenia, anemia, and cytomegalovirus infection.

The rates of different categories of infection are shown on the screen.

Safety data from REACH2 were consistent with REACH1 and the known safety profile of Jakafi.

Although the adverse reaction data reported in REACH2 is informative, the risk information as described in the Full Prescribing Information for Jakafi should be considered when making prescribing decisions.

Eleven percent of patients treated with Jakafi and 5 percent of patients treated with control therapy discontinued up to Day 28.

I would suggest considering Jakafi at the first sign of steroid-refractory acute GVHD.

We’ll turn now to safety information about Jakafi.

Narrator: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
• Advise patients about early signs and symptoms of herpes zoster and to seek early treatment
• 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 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
• 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 and edema
• Dose modifications may be required when administering Jakafi with strong CYP3A4 inhibitors or fluconazole 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

Dr Bishop: Thank you for listening.

For more about clinical studies in acute GVHD, please visit the Acute GVHD Efficacy page at hcp.jakafi.com.