Indications and Usage

Jakafi® (ruxolitinib) is indicated for treatment of steroid-refractory acute graft-versus-host disease (aGVHD) in adult and pediatric patients 12 years and older.

The data from REACH1 on this page reflect the Full Prescribing Information.

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.

REACH1: Jakafi met its primary and key secondary endpoints1,2
  • REACH1 (Ruxolitinib in PatiEnts with RefrACtory Graft-Versus-Host Disease After Allogeneic Stem Cell Transplantation) was a prospective, multicenter, open-label, single-cohort, phase 2 study evaluating Jakafi in patients, aged 12 years or older, with Grade II–IV steroid-refractory acute GVHD*
  • 71 patients were enrolled and received a starting dose of ruxolitinib at 5 mg twice daily, with an option to increase to 10 mg twice daily after 3 days in the absence of cytopenias.† There were 49 patients with acute GVHD refractory to steroids alone and evaluable for efficacy. These patients had a median age of 57 years (range, 18–72 years)
  • The primary endpoint, overall response rate (ORR)‡ at day 28 was 57% (28/49) [95% CI: 42%, 71%], including 31% of patients with complete response (CR), 4% with very good partial response (VGPR), and 22% with partial response (PR)
    • Day-28 ORR was 100% for Grade 2 GVHD, 41% for Grade 3 GVHD, and 44% for Grade 4 GVHD
  • The median duration of response, calculated from day-28 response to progression, new salvage therapy for acute GVHD or death from any cause (with progression being defined as worsening by one stage in any organ without improvement in other organs in comparison to prior response assessment) was 16 days (95% CI 9, 83). Also for the day-28 responders, the median time from day-28 response to either death or need for new therapy for acute GVHD (additional salvage therapy or increase in steroids) was 173 days (95% CI 66, NE)
  • All 71 enrolled patients were evaluable for safety. The most common hematologic adverse reactions (incidence >50%) are anemia, thrombocytopenia, and neutropenia. The most common nonhematologic adverse reactions (incidence >50%) are infections and edema
Important information for readers regarding the REACH2 study data presented in this reprint1-3

Some of the information contained in this reprint is not included in the FDA-approved Prescribing Information for Jakafi® (ruxolitinib):

  • FDA approval for Jakafi for the treatment of steroid-refractory aGVHD was based on the data from the REACH1 study
  • REACH1 was an open-label, single-arm, multicenter, phase 2 study conducted in the United States. REACH2 was a randomized, open-label, active-controlled, multicenter, phase 3 study conducted outside the United States
  • The approved dosing for ruxolitinib is based on REACH1: 5 mg twice daily with an option to increase to 10 mg twice daily after 3 days in the absence of cytopenias§; dosing in REACH2 began at 10 mg twice daily
  • In both studies, steroid-refractory aGVHD was defined as disease progression after ≥3 days of high-dose systemic steroid treatment, lack of improvement after 7 days, or failure to successfully taper steroid
    •  REACH1 also specified patients as steroid refractory if they began low-dose steroids for skin or skin plus upper GI aGVHD and developed GVHD in a new organ
    •  In REACH1, failure to taper was defined as inability to achieve a 50% taper of steroid dose, and in REACH2 as the need to increase to ≥2 mg/kg/day methylprednisolone or inability to taper below 0.5 mg/kg/day for at least 7 days
  • In REACH1, ORR was defined as complete response (CR), very good partial response (VGPR), or partial response (PR); in REACH2, ORR was defined as CR or PR (VGPR was not assessed)
  • The REACH2 publication includes efficacy endpoints not studied in REACH1 or reported in the Jakafi Prescribing Information
  • Secondary outcome measures for REACH2 should not be used to infer treatment effects as there was no prespecified plan to control for multiple comparisons
  • Jakafi has not been demonstrated to improve survival outcomes in steroid-refractory aGVHD. REACH2 was not designed to compare survival probabilities between Jakafi and control therapy
  • Although the adverse event 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

The data from REACH2 reflect the study publication linked to from this page. REACH2 data are not included in the Full Prescribing Information.

REACH2: Jakafi met its primary endpoint in patients with steroid-refractory acute graft-versus-host disease3
  • REACH2 (Ruxolitinib in PatiEnts with RefrACtory Graft-Versus-Host Disease After Allogeneic Stem Cell Transplantation 2) was an active-controlled, multicenter, open-label, randomized, phase 3 study that enrolled patients (≥12 years of age) with Grade II–IV steroid-refractory acute GVHD
  • A total of 309 patients were randomized to either ruxolitinib 10 mg twice daily (n = 154) or control (n = 155), which consisted of the investigator’s choice of 9 frequently used therapies∥
  • Overall response rate (ORR) at day 28 (primary endpoint) was 62% in the ruxolitinib arm vs 39% in the control arm (P <0.001)
  • The safety profile from REACH2 was consistent with previous studies, including REACH1. Adverse events (AEs) up to day 28 were broadly similar between ruxolitinib and control. The most common AEs of any grade (up to day 28) were thrombocytopenia (33% in the ruxolitinib arm and 18% in the control arm), anemia (30% in the ruxolitinib arm and 28% in the control arm), and cytomegalovirus infection (26% in the ruxolitinib arm and 21% in the control arm)#

AE, adverse event; ANC, absolute neutrophil count; BAT, best available therapy; CR, complete response; MAGIC, Mount Sinai Acute GVHD International Consortium; ORR, overall response rate; PR, partial response; VGPR, very good partial response.

*Patients had Grade II–IV aGVHD defined according to the MAGIC criteria, occurring after allogeneic hematopoietic stem cell transplantation.1

†≥50% decrease in platelet counts and/or absolute neutrophil count relative to day 1.1

‡Defined as the proportion of patients demonstrating a CR, VGPR, or PR.1

§If ANC and/or platelet counts are not decreased by 50% or more relative to the first day of dosing with Jakafi.1

∥Control therapy included antithymocyte globulin, extracorporeal photopheresis, mesenchymal stromal cells, low-dose methotrexate, mycophenolate mofetil, mammalian target of rapamycin (mTOR) inhibitor (everolimus or sirolimus), etanercept, or infliximab.3

ORR at day 28 was defined as the proportion of patients with complete or a partial response.3

#A distinction between cytomegalovirus infection and reactivation was not made in this study.3

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 click here to see Full Prescribing Information for Jakafi.

Please see hcp.jakafi.com for more information and educational resources.

Financial disclosures

The REACH2 study was sponsored by Novartis. The authors of this publication disclosed the following related to Incyte Corporation or Novartis in the 36 months prior to publication: Drs Gandhi, Mahuzier, Wilke, and Xu were employees of Incyte Corporation. Drs Gandhi and Wilke reported owning Novartis stock. Drs Gandhi, Mohty, Zuckerman, Mahuzier, Socie, Wagner, Niederwieser, von Bubnoff, and Zeiser reported financial interests from Novartis. Drs Zeiser and Socie reported financial interests from Incyte. All authors report nonfinancial support for manuscript preparation from Novartis. Additional disclosure information is located at https://www.nejm.org/doi/suppl/10.1056/NEJMoa1917635/suppl_file/nejmoa1917635_disclosures.pdf.

References: 1. Jagasia M, Perales MA, Schroeder MA, et al. Blood. 2020;135(20):1739-1749. 2. Jakafi Prescribing Information. Wilmington, DE: Incyte Corporation. 3. Zeiser R, von Bubnoff N, Butler J, et al. N Engl J Med. 2020;382(19):1800-1810.

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  • Indications and Usage / Important Safety Information