Narrator: The REACH Studies in Steroid-Refractory Acute GVHD
Part 1: Overall Response Rate, Including by Grade and Organ
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 medical oncologist specializing in hematopoietic stem cell transplantation in the Chicago area. I’d like to share some information with you about a serious disease called acute graft-versus-host disease, or acute GVHD, that may progress rapidly in some patients.
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: The efficacy of Jakafi in steroid-refractory acute GVHD was assessed in both Phase 2 and Phase 3 studies, called the REACH studies.
Approval of Jakafi for use in steroid-refractory acute GVHD was based on positive results of the Phase 2 REACH1 study.
Let’s take a look at REACH1, a prospective, open-label, single-arm, multicenter phase 2 study of Jakafi for patients 12 years of age and older with steroid-refractory acute GVHD.
In REACH1, the dose of Jakafi could be increased from the starting dose of 5 mg twice daily to 10 mg twice daily after 3 days in the absence of toxicity. Of note, 59 percent of patients (27 of 46) were receiving Jakafi at a dose of 10 mg twice daily at Day 7.
The primary endpoint of REACH1 was overall response rate at day 28, which included patients with a complete response, very good partial response, or partial response as defined by the Center for International Blood and Marrow Transplant Research criteria.
Overall responses were achieved for the majority of patients treated with Jakafi at Day 28.
As you can see, the overall response rate at Day 28 was 57 percent, meaning that 28 of 49 patients had complete, very good partial, or partial response.
In a subgroup analysis, overall response rate varied by grade. While the subgroup contained only 13 patients, the overall response rate in patients with Grade II disease was 100 percent.
A subgroup analysis examining overall response rate by organ was also performed. And as you can see from the data on the screen, responses to Jakafi were seen across all organs with various overall response rates.
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, Jakafi demonstrated significantly higher Day 28 responses vs control therapy.
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.
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
- 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 available at http://www.jakafi.com/pdf/prescribing-information.pdf.
Dr Bishop: You can learn more about Jakafi for patients with steroid-refractory acute GVHD by visiting hcp.Jakafi.com.
Thanks for watching.
The REACH Studies in Steroid-Refractory aGVHD:
Overall Response Rate, Including by Grade and Organ
The REACH Studies in
Overall Response Rate, Including by Grade and Organ
Oncologist Dr Michael Bishop reviews the primary efficacy data and safety profile from the REACH1 and REACH2 clinical studies evaluating Jakafi® (ruxolitinib) in patients with steroid-refractory aGVHD.
Data from REACH2 are not included in the FDA-approved Prescribing Information for Jakafi. FDA approval for Jakafi for the treatment of steroid-refractory aGVHD was based on data from the REACH1 study.
aGVHD, acute graft-versus-host disease; REACH, Ruxolitinib in PatiEnts with RefrACtory Graft-Versus-Host Disease After Allogeneic Stem Cell Transplantation.
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Michael R Bishop, MD
Michael R Bishop, MD
Michael R Bishop, MD