For your patients with steroid-refractory acute graft-versus-host disease (GVHD)1

Proactively Identify Steroid-Refractory Acute GVHD (aGVHD) and Treat Differently

For your patients with steroid-refractory acute graft-versus-host disease (GVHD)1

Proactively Identify Steroid-Refractory Acute GVHD (aGVHD) and Treat Differently

Response to Systemic Daily Steroids

STEROID-REFRACTORY PATIENTS CAN BE IDENTIFIED AS EARLY AS 3 DAYS AFTER STARTING TREATMENT

Additional Therapy May Be Required

Approximately half of patients with aGVHD will not achieve an adequate response to steroids.2-6

Image of a chart showing the standard of care for initial aGVHD therapy: Systemic daily steroids Image of a chart showing the standard of care for initial aGVHD therapy: Systemic daily steroids

In each of 2 studies that directly compared outcomes in the steroid-refractory and steroid-dependent populations, both populations had similarly poor outcomes.7,8

Patients Can Be Identified In As Early As 3 Days

Patients with steroid-refractory aGVHD can be identified in as early as 3 days after starting treatment with steroids.6

Image of a chart showing EBMT-NIH-CIBMTR Task Force Guidance Defines Response to Steroids Image of a chart showing EBMT-NIH-CIBMTR Task Force Guidance Defines Response to Steroids

CIBMTR, Center for International Blood and Marrow Transplant Research; EBMT, European Society for Blood and Marrow Transplantation; NIH, National Institutes of Health.

MAGIC Criteria for aGVHD

Grading can help guide decisions on treatment initiation and when alternative treatment should be considered.3,9

The REACH1 (Ruxolitinib in PatiEnts with RefrACtory Graft-Versus-Host Disease After Allogeneic Stem Cell Transplantation) Study

Grading of aGVHD was used in REACH1 based on MAGIC criteria, with disease assessment of the skin, liver and gastrointestinal tract, and organ staging that is combined to yield an overall grade based on severity. Patients enrolled in REACH1 had Grade II to IV aGVHD1,10:

Image of a chart showing MAGIC aGVHD Grading System, as used in REACH1 Image of a chart showing MAGIC aGVHD Grading System, as used in REACH1

REACH1 is a prospective, open-label, single-cohort, multicenter study of Jakafi in patients with steroid-refractory aGVHD.

Image of the REACH1 Study Design Image of the REACH1 Study Design

BID, twice daily; CIBMTR, Center for International Blood and Marrow Transplant Research; GI, gastrointestinal; MAGIC, Mount Sinai Acute GVHD International Consortium; MP, methylprednisolone; ORR, overall response rate; REACH, Ruxolitinib in PatiEnts with RefrACtory Graft-Versus-Host Disease After Allogeneic Stem Cell Transplantation.

aPatients had Grade II to IV aGVHD defined according to the MAGIC criteria, occurring after allogeneic hematopoietic stem cell transplant.1
bSafety analysis based on all patients who received ruxolitinib (N = 71); 49 patients were eligible for efficacy analysis.12
cIf hematologic parameters were stable and treatment-related toxicity was not observed.12
dDefined as the proportion of patients who had a complete response, partial response, or very good partial response at day 28. GVHD responses were assessed based on the CIBMTR definitions.1

Patients Enrolled and Evaluated in REACH1

71 patients enrolled in REACH1 and received Jakafi1:

  • 49 patients were refractory to corticosteroids alone and were included in efficacy analyses
  • 22 patients were not included in efficacy analyses because:
    • they received ≥2 prior anti-GVHD therapies (12 patients)
    • they did not receive an adequate amount of corticosteroids (10 patients)12

Patients with steroid-refractory aGVHD in REACH1 included those who were steroid-dependent. They were defined as patients who12:

  • Had disease that progressed after 3 days of ≥2 mg/kg/day of methylprednisolone or equivalent
  • Had disease that failed to improve after 7 days of ≥2 mg/kg/day of methylprednisolone or equivalent
  • Were treated with ≥1 mg/kg/day of methylprednisolone for skin GVHD or skin plus upper gastrointestinal (GI) GVHD and developed disease in an additional organ
  • Were unable to achieve a 50% taper of their steroid dose without a return of their GVHD

Get REACH1 efficacy results.

References

  1. Jakafi Prescribing Information. Wilmington, DE: Incyte Corporation.
  2. Dignan FL, Clark A, Amrolia P, et al. Diagnosis and management of acute graft-versus-host disease. Br J Haematol. 2012;158(1):30-45.
  3. Martin PJ, Rizzo JD, Wingard JR, et al. First- and second-line systemic treatment of acute graft-versus-host disease: recommendations of the American Society of Blood and Marrow Transplantation. Biol Blood Marrow Transplant. 2012;18(8):1150-1163.
  4. Hill L, Alousi A, Kebriaei P, et al. New and emerging therapies for acute and chronic graft versus host disease. Ther Adv Hematol. 2018;9(1):21-46.
  5. MacMillan ML, Weisdorf DJ, Wagner JE, et al. Response of 443 patients to steroids as primary therapy for acute graft-versus-host disease: comparison of grading systems. Biol Blood Marrow Transplant. 2002;8(7):387-394.
  6. Schoemans HM, Lee SJ, Ferrara JL, et al. 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.
  7. Mendoza KA, Chen H, Englehardt BG, et al. Similar outcomes in early failure steroid dependent acute GvHD and upfront steroid refractory acute GvHD. Presented at: 59th American Society of Hematology (ASH) Annual Meeting and Exposition; December 9-12, 2017; Atlanta, GA; Abstract 1975.
  8. Das-Gupta E, Greinix H, Jacobs R, et al. Extracorporeal photopheresis as second-line treatment for acute graft-versus-host disease: impact on six-month freedom from treatment failure. Haematologica. 2014;99(11):1746-1752.
  9. Nassereddine S, Rafei H, Elbahesh E, et al. Acute graft versus host disease: a comprehensive review. Anticancer Res. 2017;37(4):1547-1555.
  10. Harris AC, Young R, Devine S, et al. International, multicenter standardization of acute graft-versus-host disease clinical data collection: a report from the Mount Sinai Acute GVHD International Consortium. Biol Blood Marrow Transplant. 2016;22(1):4-10.
  11. Jagasia M, Zeiser R, Arbushites M, et al. Ruxolitinib for the treatment of patients with steroid-refractory GVHD: an introduction to the REACH trials. Presented at: 60th American Society of Hematology (ASH) Annual Meeting and Exposition; December 1-4, 2018; San Diego, CA. Abstract 601.
  12. Data on file. Incyte Corporation. Wilmington, DE.

Indications and Usage

Jakafi is indicated for treatment of polycythemia vera (PV) in adults who have had an inadequate response to or are intolerant of hydroxyurea.

Jakafi is indicated for treatment of intermediate or high‐risk myelofibrosis (MF), including primary MF, post–polycythemia vera MF and post–essential thrombocythemia MF in adults.

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

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
  • Advise patients about early signs and symptoms of herpes zoster and to seek early treatment
  • 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 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
  • 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 and edema
  • Dose modifications may be required when administering Jakafi with strong CYP3A4 inhibitors or fluconazole 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.