Hi, I'm Dr Preet M. Chaudhary and I'm Chief of Hematology and Director of Bone Marrow Transplant and Cell Therapy at USC Norris Comprehensive Cancer Center.

Today, I will speak about the importance of intervening at the first signs of initial systemic treatment failure in chronic GVHD.

At our institution, we consider cGVHD a serious threat to patient survival if left untreated. Therefore, we follow an aggressive approach and do not delay treatment of cGVHD.

Our goal, first and foremost, is to intervene with Jakafi at the first signs of initial systemic treatment failure and to not let cGVHD smolder over time.

In practice, we monitor skin disease as a surrogate marker for disease progression—as cGVHD is a systemic disease, and it may progress before it becomes symptomatic in difficult-to-assess organs such as the lungs.

Our second goal is to help prevent disease progression by keeping patients on an effective therapy for ongoing response to treatment.

This is why we again turn to Jakafi. While we assess the benefits of treatment versus the risks in each patient, we believe that intervening early with Jakafi is important.

In our institution, advanced practice providers take charge in the outpatient follow-ups. We ask simple and objective questions to tease out symptoms that may identify clinical characteristics of disease progression, early in the course of the disease. For this, we assess the most commonly involved organs.

For skin, we assess for skin rash, any changes in pigmentation or overall appearance, and for any signs of sclerosis.

For eyes, we ask about any discomfort, sensation of dryness or grittiness, or watery eyes, which also indicates irritation.

For mouth, we may ask, “Do you have any sensitivity to spicy food or issues brushing your teeth?” We also examine the mucosal lining of the oral cavity.

For GI system, we ask about changes in stool patterns and investigate underlying causes of weight loss. We may ask, “Do you have to drink more water in order for food to go down?”

We look at labs for signs of liver dysfunction.

Considering joints, we may ask, “Do you feel any joint discomfort in the morning or tightness when you walk around?”

To assess lung involvement, we may ask, “Are you able to speak a full sentence without stopping for breath?”

We also ask about sexual health and activities of daily living to round out a thorough systemic review.

We generally start our patients on 1 mg/kg/day prednisone, and we are looking for improvement within a few days. If, however, we see no change in symptoms, following the NIH criteria, we switch to Jakafi very quickly so that we can potentially halt disease progression and have more flexibility on tapering steroids.

Support for our use of Jakafi comes from the REACH3 trial, a phase 3, randomized, open-label, multicenter study of Jakafi vs best available therapy, or BAT, in patients with steroid-refractory cGVHD. The starting dose of Jakafi was 10 mg twice daily, and crossover from BAT was permitted on or after week 24 if patients progressed, had a mixed or unchanged response, developed toxicity to BAT, or experienced a cGVHD flare.

We like to show patients the primary endpoint data to demonstrate that patients on Jakafi achieved significantly greater overall response compared with BAT at week 24, with an overall response rate of 49.7% compared to 25.6%. We can also take a look at ORRs at week 24 with Jakafi and individual BATs. Patients often feel discouraged when you add a second-line therapy because adding another treatment makes patients feel like they are taking a step back. We use these data to show that with Jakafi we have the potential to halt disease progression.

With Jakafi, you see a better response compared with BAT, regardless of baseline disease severity. It’s important to note that there was a better chance of seeing a response when Jakafi was initiated in patients with moderate disease.

As I mentioned earlier, cGVHD can smolder and progress out of control. For us, these data support our approach to aggressively intervene early with Jakafi, in appropriate patients, so that we have a better chance of halting disease progression.

Looking at a more granular level, more patients achieved a higher response with Jakafi regardless of the organs involved.

Chronic GVHD is frequently a systemic disease. The advantage of using skin as a marker is that it is relatively easy to assess the state of the disease and its response to treatment as compared to internal organs, for example, the lungs. Even patients themselves can monitor the progression of the disease. Seeing that Jakafi is effective across the board regardless of the organs involved gives us the confidence to initiate Jakafi at early changes in skin disease to really get the opportunity to help control cGVHD.

My second goal of treatment for cGVHD is to try to prevent disease progression by keeping patients on an effective therapy to achieve an ongoing durable treatment response. This can be measured using failure-free survival, which is a composite endpoint measuring time to recurrence of underlying disease, start of new systemic treatment for chronic GVHD or death, whichever comes first.

As seen here, the estimated probability of failure-free survival was 74.9% at 6 months and 64% at 12 months for patients on Jakafi.

Median failure-free survival with Jakafi was not reached.

This provides further evidence to support intervention with Jakafi at the first signs of initial systemic treatment failure and to keep appropriate patients on Jakafi to achieve ongoing response. A durable response is critical for helping to prevent long-term organ damage.

Moving on to safety, 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.

In summary, to potentially halt disease progression and help patients achieve an ongoing response to treatment, we take an aggressive approach and intervene with Jakafi, in appropriate patients, at the first signs of initial systemic treatment failure in cGVHD.

Thank you for listening. Now, let’s take the opportunity to review important 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.