Hi, I'm Karolina Faysman, and I'm an advanced oncology certified nurse practitioner at the Ronald Reagan UCLA Medical Center and Santa Monica UCLA Medical Center.

Today, I’ll speak about the importance of intervening at the first signs of initial systemic treatment failure for chronic GVHD.

Chronic GVHD is the primary cause of morbidity and non-relapse mortality after allogeneic hematopoietic cell transplantation.

Once chronic GVHD occurs, disease trajectory can be rapid and unpredictable. Like a biological point of no return, once you miss the earlier stages of inflammation, the tissue damage may become irreversible and organ function cannot be regained. For example, with any loss of the epidermis, patients will be dealing with the consequences for the rest of their lives.

Therefore, my treatment management goals are to arrest the development of chronic GVHD early on and prevent progression. Recognizing early signs and symptoms is the first step to intervention.

During routine visits with my patients, I literally go system by system, top to bottom, in order not to miss anything.

Starting from the top, I look for new onset of dryness in eyes or changes in visual acuity. The eyes are easily overlooked by patients because they may not associate dry eyes with chronic GVHD.

With the mouth, I’m looking for reports of dryness, new sores, sensitivity to normally tolerated foods and reduced mouth opening, or signs of dysphagia. I may ask, “Do you have to drink more water in order for food to go down?”

With skin, early signs often includes lichenoid changes, new patches of dry skin, tightness of the skin, or formation of lesions. I particularly look for changes on their upper trunk, neck, and the posterior part of their torso.

Eyes, mouth, and skin round up the organs with the most common early signs or symptoms of chronic GVHD.

Moving down, considering the lungs, I may ask, “Are you able to speak a full sentence without stopping for breath?”

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

For GI, I may ask, “Are there any changes in stool color or formation?”

It’s also important to discuss topics that are often stigmatized such as sexual health.

In addition, patients need to stay vigilant. Education on the early signs and symptoms of chronic GVHD, and how they evolve should be a continuous effort, as the potential for chronic GVHD does not end at year 1 or 8, post-transplant.

In my practice, I tell my patients to track changes in symptoms in between their visits and call me when they experience any of their changes for more than a week.

When I initiate first-line steroid therapy, I’m looking for a response within that first week. For example, if a chronic GVHD patient presents with rash and is started on high dose steroids, I expect to see objective improvements during examination, as well as subjective improvements in rash and discomfort within the first week. In my experience, if I don’t see at least some response within the first week or I am unable to taper steroid use, I intervene with Jakafi, as opposed to taking the chance that the disease could become more severe.

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

As I mentioned before, my main goal in managing my patients with chronic GVHD is to arrest development early and prevent progression to severe chronic GVHD.

If we look at the primary endpoint at week 24, significantly more patients achieved a response with Jakafi compared to BAT at week 24, with an overall response rate of 49.7% compared to 25.6%.

This higher response with Jakafi is also seen through week 24, with an ORR of 70% vs 57%.

Initiation of Jakafi in the moderate stages of disease is associated with higher response rates, as you can see here.

These data are no surprise to me as they reflect my own experience and reinforce the importance of intervening early with Jakafi as a second-line therapy.

It is reassuring to see that the impact of Jakafi is consistent across all organs, including the skin, mouth, and eyes, where earlier signs and symptoms are most common. Response was also seen in more challenging organs to treat, such as the lungs.

For appropriate patients this data continues to support early intervention during the inflammation stage of cGVHD.

Another important reason for early intervention with Jakafi is so my patients may be able to achieve sustained benefits and lower their risk of relapse or mortality over time. To do this, I start my patients on 10 mg BID to achieve a response. After achieving a desired response, I maintain them on the lowest tolerable dose over time to help prevent flare-ups.

In REACH3, estimated probability of failure-free survival with Jakafi–defined as relapse, needing additional treatment for chronic GVHD, or death–was 74.9% at 6 months and 64% at 12 months. Median failure-free survival with Jakafi was not reached. Jakafi’s safety profile is well established. No new safety signals were observed in REACH3.

In my practice, my approach to managing patients with chronic GVHD is to intervene early to potentially control progression and prevent any irreversible damage. I take a thorough history to uncover any early signs and symptoms and initiate second-line therapy with Jakafi at the first sign of systemic treatment failure. Early intervention with Jakafi allows my patients to potentially achieve better response and sustained benefits from treatment.

Thank you for listening.

Let’s take the opportunity to review the 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.