TREATMENT PERSPECTIVES®

Patients with steroid-refractory cGVHD may be identified as early as 1 week from the start of steroid treatment.1

Respond to a question about cGVHD treatment

QUESTION 1 of 2

How would you manage a patient in your clinic with chronic GVHD who, after one week on 1 mg/kg of steroids with initial improvement, now presents with new-onset mild skin involvement?

YOUR ANSWER

cGVHD=chronic graft-versus-host disease.

Thank you for answering.

Jakafi® (ruxolitinib) is indicated for treatment of cGVHD after failure of one or two lines of systemic therapy in adult and pediatric patients 12 years and older.2

REACH3 Primary Endpoint: ORR at Week 24

  • 49.7% (82/165) with Jakafi vs 25.6% (42/164) with BAT (OR, 2.99; 95% Cl, 1.86-4.80; P<0.0001)3*†

ORR Through Week 24

  • 70% (116/165) with Jakafi vs 57% (94/164) with BAT2‡
    • In the Jakafi Prescribing Information, efficacy was based on ORR through week 24 (cycle 7, day 1)2

REACH3 post hoc analysis: Impact of early intervention on ORR with Jakafi vs BAT4

Overall Response at Week 24 by Time-to-Treat Initiation From SR Diagnosisa

Bar Chart

aNo significant differences were observed between ruxolitinib time-to-treatment subgroups for ORR, best BOR, or DOR.4

SEE THE SAFETY DATA

REACH3 was a randomized, open-label, multicenter, phase 3 study of Jakafi vs BAT in patients with SR cGVHD (N=329).2,3§‖¶ The starting dose for Jakafi was 10 mg BID. 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 cGVHD flare.3

CLICK HERE TO LEARN MORE ABOUT EARLY INTERVENTION

PROFESSIONAL RESOURCES

Jakafi HCP Site Prescribing Information

*ORR was defined as the proportion of patients with CR or PR at week 24, according to 2014 NIH consensus criteria.3

†One-sided P value, OR, and 95% Cl were calculated using stratified Cochran-Mantel-Haenszel test, stratifying for moderate and severe cGVHD.3

‡Defined as the proportion of patients who achieved CR or PR through week 24 (cycle 7, day 1), according to 2014 NIH consensus criteria.2

§Patients included in the study were 12 years and older, had undergone allogeneic hematopoietic stem cell transplant from any donor source/type, and had evident myeloid and platelet engraftment.2,3

‖BATs included ibrutinib, ECP, low-dose MTX, MMF, rituximab, everolimus, sirolimus, imatinib, infliximab, and pentostatin.2

SR disease was defined as lack of response or disease progression after ≥1 week of prednisone 1 mg/kg/day, disease persistence without improvement after ≥4 weeks of prednisone >0.5 mg/kg/day or 1 mg/kg every other day, or increase in prednisone dose to >0.25 mg/kg/day after 2 unsuccessful attempts to taper the dose.3,5

BAT=best available therapy; BID=twice daily; BOR=best overall response; cGVHD=chronic graft-versus-host disease; Cl=confidence interval; CR=complete response; DOR=duration of response; ECP=extracorporeal photopheresis; MMF=mycophenolate mofetil; MTX=methotrexate; NIH=National Institutes of Health; OR=odds ratio; ORR=overall response rate; PR=partial response; REACH=Ruxolitinib in patiEnts with refrACtory graft-versus-Host disease after allogeneic stem cell transplantation; SR=steroid-refractory.

INDICATION 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 see Full Prescribing Information for Jakafi.

Reference:

1. Schoemans HM, Lee SJ, Ferrara JL, et al; for the EBMT Transplant Complications Working Party and the EBMT−NIH−CIBMTR GvHD Task Force. EBMT–NIH–CIBMTR Task Force position statement on standardized terminology & guidance for graft-versus-host disease assessment. Bone Marrow Transplant. 2018;53(11):1401-1415.

References:

1. Schoemans HM, Lee SJ, Ferrara JL, et al; for the EBMT Transplant Complications Working Party and the EBMT−NIH−CIBMTR GvHD Task Force. EBMT–NIH–CIBMTR Task Force position statement on standardized terminology & guidance for graft-versus-host disease assessment. Bone Marrow Transplant. 2018;53(11):1401-1415. 2. Jakafi Prescribing Information. Wilmington, DE: Incyte Corporation. 3. Zeiser R, Polverelli N, Ram R, et al; for the REACH3 Investigators. Ruxolitinib for glucocorticoid-refractory chronic graft-versus-host disease. N Engl J Med. 2021;385(3):228-238. Supplementary appendix available at: https://www.nejm.org/doi/full/10.1056/NEJMoa2033122. 4. Zeiser R, Xue Z, Bhatt V, Galvin J, Locatelli F. Early versus late treatment with ruxolitinib in patients with steroid-refractory chronic graft-versus-host disease: a post hoc analysis from the randomized, phase 3 REACH3 study. Poster presented at: 64th American Society of Hematology (ASH) Annual Meeting and Exposition; December 10-13, 2022; New Orleans, LA. 5. Data on file. Incyte Corporation. Wilmington, DE.