For steroid-refractory acute graft-versus-host disease (GVHD) in adult and pediatric patients 12 years of age and older1

Identify Steroid-Refractory Acute GVHD (aGVHD) Early
and Intervene With Jakafi

For steroid-refractory acute graft-versus-host disease (GVHD) in adult and pediatric patients 12 years of age and older1

Identify Steroid-Refractory Acute GVHD (aGVHD) Early
and Intervene With Jakafi

Steroid-Refractory aGVHD Is a Major Threat to Transplant Outcomes

To learn more about early identification of steroid-refractory aGVHD, CLICK HERE.

GVHD

Graft-versus-host disease (GVHD) is a potentially life-threatening complication of allogeneic hematopoietic stem cell transplant (allo-HSCT) that occurs when donor immune cells attack a patient’s tissues.2

GVHD remains a major cause of morbidity and mortality for allo-HSCT recipients.3,4

There is distinct pathophysiology and presentation of acute GVHD and chronic GVHD. Acute GVHD can occur at any time, but often occurs in the first few months after transplant.5

Image of a chart showing the characteristics of acute GVHD and chronic GVHD Image of a chart showing the characteristics of acute GVHD and chronic GVHD

GI, gastrointestinal.

Acute GVHD is characterized by inflammatory response driven by alloreactive donor T cells and may affect the skin, gastrointestinal tract, and liver.5,7-9

Image of a chart showing the pathogenesis of acute GVHD Image of a chart showing the pathogenesis of acute GVHD

Diagnosis and Management of Acute GVHD

Diagnosis is based on clinical signs and symptoms as well as biopsies and laboratory tests.11 Grading and staging of aGVHD may help to guide management.9,13

The standard of care for initial aGVHD therapy is systemic daily steroids.13-17

However, approximately half of patients with aGVHD will not achieve an adequate response to steroids.13-17 These patients with an incomplete initial response may have steroid-refractory aGVHD, and require additional therapy.13-17

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.18,19

Identify patients with steroid-refractory aGVHD. LEARN MORE.

References

  1. Jakafi Prescribing Information. Wilmington, DE: Incyte Corporation.
  2. McDonald-Hyman C, Turka LA, Blazar BR. Advances and challenges in immunotherapy for solid organ and bone marrow transplantation. Sci Transl Med. 2015;7:280rv2. doi: 10.1126/scitranslmed.aaa6853.
  3. Garnett C, Apperley JF, Pavlů J. Treatment and management of graft-versus-host disease: improving response and survival. Ther Adv Hematol. 2013;4(6):366-378.
  4. Renteria AS, Levine JE, Ferrara JL. Development of a biomarker scoring system for use in graft-versus-host disease. Biomark Med. 2016;10(8):793-795.
  5. Filipovich AH, Weisdorf D, Pavletic S, et al. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and Staging Working Group report. Biol Blood Marrow Transplant. 2005;11(12):945-956.
  6. Jagasia MH, Greinix HT, Arora M, et al. National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: I. The 2014 Diagnosis and Staging Working Group report. Biol Blood Marrow Transplant. 2015 Mar;21(3):389-401.
  7. Blazar BR, Murphy WJ, Abedi M. Advances in graft-versus-host disease biology and therapy. Nat Rev Immunol. 2012;12(6):443-458.
  8. Pierini A, Alvarez M, Negrin RS. NK cell and CD4+FoxP3+ regulatory T cell based therapies for hematopoietic stem cell engraftment. Stem Cells Int. 2016;2016:9025835. doi:10.1155/2016/9025835.
  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. Flowers MED, Martin PJ. How we treat chronic graft-versus-host disease. Blood. 2015;125(4):606-615.
  11. Pavletic SZ, Fowler DH. Are we making progress in GVHD prophylaxis and treatment? Hematology. 2012;2012:251-264.
  12. Ferrara J, Levine JE, Reddy P, et al. Graft-versus-host disease. Lancet. 2009;373(9674):1550-1561.
  13. 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.
  14. 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.
  15. 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.
  16. 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.
  17. 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.
  18. 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.
  19. 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.

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.