Hello, I’m Dr Haris Ali, hematologist-oncologist, stem cell transplant physician, and currently associate professor in the Department of Hematology and Hematopoietic Cell Transplantation at City of Hope in Duarte, California.

In my practice, I have a particular concern for patients who develop chronic graft-versus-host disease, or GVHD, following a hematopoietic stem cell transplant.

My treatment goals for these patients are first, identify chronic GVHD as early as possible.

Second, alleviate symptoms by achieving an improvement of GVHD manifestations.

And third, minimize exposure to steroids. To achieve these goals, I intervene with Jakafi at the first signs of initial systemic treatment failure.

Today, I would like to review data from REACH3 that have become available. I am excited to share these data with you and how they impact my management of patients with chronic GVHD.

Jakafi is a kinase inhibitor indicated for the treatment of chronic GVHD after failure of 1 or 2 lines of systemic therapy in adult and pediatric patients 12 years and older.

REACH3 was the pivotal trial that compared Jakafi versus best available therapy in patients with moderate to severe steroid-refractory or steroid-dependent chronic GVHD.

Adverse reactions and selected lab abnormalities up to week 24 are shown here.

In the REACH3 trial, no new safety signals were observed for Jakafi.

The results from REACH3 gave me confidence in Jakafi to help reach my treatment goals by increasing the patient’s chance of achieving a partial or complete response.

Patients with chronic GVHD can develop irreversible symptoms, impacting the eyes, mouth, joints, and lungs. I educate patients before their transplant about potential acute and chronic GVHD scenarios that could arise.

In my experience, patients who had acute GVHD or who are on tapering doses of immunosuppression have a higher risk of developing chronic GVHD later and require close monitoring so we can identify the manifestations as early as possible. The longer you wait to treat, the greater the potential for symptoms to become permanent and debilitating.

For this reason, early assessment, and intervention with Jakafi, if the patient becomes steroid refractory or steroid dependent, is important.

My experience has taught me the importance of early intervention on second-line therapy. This is supported by the REACH3 data, including the early-vs-late ad hoc analysis. Note that, according to the NIH, steroid-refractory chronic GVHD can be identified as early as 1 week from the start of systemic treatment.

Following the REACH3 study, there was a post hoc analysis of the data that examined the overall response rate at week 24, best overall response at any time, and duration of response across subgroups of patients who had been categorized too early, late, or very late after being diagnosed as steroid refractory.

Among patients who received treatment with Jakafi, at week 24, 54.5% of patients who were diagnosed as steroid refractory less than 14 days prior to randomization achieved an overall response, with 10.2% achieving a full response and 44.3% achieving a partial response.

Overall response was 46.7% in patients categorized as late, with 3.3% achieving a full response and 43.3% achieving a partial response. And in the group of patients categorized as very late, 42.6% of patients achieved an overall response, with 2.1% achieving a full response and 40.4% achieving a partial response.

In my many years of experience, the responses demonstrated in the REACH3 trial align with what I’m seeing in my clinical practice. In fact, our institution has published our real-world evidence that these response rates in the trial are consistent with observations in practice.

In my practice, I monitor patients closely when starting them on steroids. If I don’t see a response within 7 days, I initiate a second-line treatment, with Jakafi being my preferred choice.

I do this because it’s important to move to second-line therapy as quickly as is appropriate to achieve the patient outcomes we just discussed.

Following the primary analysis of REACH3, patients either on Jakafi or those who had crossed over to Jakafi could enter a 3-year follow-up study that looked at failure-free survival and duration of response. This became the final efficacy and safety analysis of Jakafi.

In the clinic, failure-free survival and duration of response are important because they can be signs that the patient is improving and able to tolerate treatment. This continues to support my decision to intervene with Jakafi at first signs of steroid-refractory or dependent chronic GVHD.

At the end of REACH3, 73 patients who had been randomized to Jakafi and 24 of the patients who were randomized to best available therapy and then crossed over to Jakafi after 24 weeks entered the long-term follow-up.

At the 3-year follow-up, the probability of sustained failure-free survival was 3 times higher with patients on Jakafi vs those who received best available therapy. Additionally, the median failure-free survival was 38.4 months for Jakafi and 5.7 months for best available therapy.

When we examine the duration-of-response graph, we can see that patients on Jakafi achieved 2 times higher probability of maintaining response than patients who received best available therapy.

The median duration of response was not reached for Jakafi and was 6.4 months for best available therapy.

This is significant to me because these data support early intervention and support the long-term durability of response associated with Jakafi in patients with chronic GVHD.

I found it interesting to see the plateaus in the failure-free-survival and duration-of-response graphs, as they support my preference for keeping patients on Jakafi for an extended period with the hope that I can eventually taper them off.

In the 3-year final analysis, there were no new safety signals found, and safety was consistent with earlier studies. The most common adverse event of any grade, and grade 3 or higher in all groups, was anemia.

Pneumonia was the most common serious adverse event in all groups and the most common adverse event leading to discontinuation of Jakafi.

Overall, in my opinion, the failure-free-survival and duration-of-response data from the REACH3 trial assure that Jakafi can potentially help my patients achieve a durable and lasting response over an extended period of time, and potentially impact their quality of life.

For additional information, please reach out to your representative.

Please see full prescribing information for Jakafi available at Jakafi.com.

Jakafi (ruxolitinib) is available in 5-mg, 10-mg, 15-mg, 20-mg, and 25-mg tablets.

INDICATIONS AND USAGE

Jakafi 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.