REACH1: A Prospective, Open-label, Single-cohort, Multicenter Study of Jakafi in Patients With Steroid-refractory aGVHD

  • Patients included in the trial had steroid-refractory acute GVHD Grades II–IV (Mount Sinai Acute GVHD International Consortium [MAGIC] criteria)1
  • FDA approval for Jakafi in steroid-refractory aGVHD was based on the REACH1 trial1

Image of REACH1: A Prospective, Openm-Label, Single-Cohort, Multicenter Study

Image of REACH1: A Prospective, Openm-Label, Single-Cohort, Multicenter Study

Patients with steroid-refractory aGVHD were defined as those who3:

  • 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

49 patients with aGVHD refractory to steroids alone were evaluable for efficacy

REACH1: Day 28 Responses Were Achieved in the Majority of Patients

Image of Primary Endpoint: ORR of 57% at Day 28

Image of Primary Endpoint: ORR of 57% at Day 28

CI, confidence interval; CR, complete response; ORR, overall response rate; PR, partial response; VGPR, very good partial response.

Image of Subgroup Analysis:ORR at Day 28 by Baseline aGVHD Grade

Image of Subgroup Analysis:ORR at Day 28 by Baseline aGVHD Grade

ORR, overall response rate.

Endpoint Definitions3

Complete response

  • Score of 0 for GVHD grading in all evaluable organs*

Very good partial response

  • Skin: no rash or residual erythematous rash involving <25% of body surface, without bullae (residual faint erythema [redness of skin] and hyperpigmentation do not count)
  • Liver: total serum bilirubin concentration <2 mg/dL, or <25% baseline at enrollment
  • Gut: tolerating food or enteral feeding, predominantly formed stools, no overt GI bleeding or abdominal cramping, no more than occasional nausea or vomiting

Partial response

  • Improvement in 1 stage in ≥1 organ involved with GVHD symptoms without progression in others

*For a response to be scored as complete response at Day 28 or later, the patient must still be in complete response on that day and have had no intervening additional therapy for an earlier progression, mixed response, or no response.

For a response to be scored as partial response at Day 28 or later, the patient must still be in partial response on that day and have had no intervening additional therapy for an earlier progression, mixed response, or no response.

Safety analysis based on all patients who received ruxolitinib (N=71)

REACH1 Safety Results for Jakafi

Non-hematologic adverse reactions occurring in ≥15% of patients1,a

Image of a chart that shows Adverse Events of the REACH1 Safety Profile of Jakafi (ruxolitinib)

Image of a chart that shows Adverse Events of the REACH1 Safety Profile of Jakafi (ruxolitinib)

REACH1 Clinically Relevant Laboratory Abnormalities
Selected Laboratory Abnormalities Worsening from Baseline1,a

Image of a chart that shows Selected Laboratory Abnormalities Worsening from Baseline (REACH1)

Image of a chart that shows Selected Laboratory Abnormalities Worsening from Baseline (REACH1)

Discontinuations Due to Adverse Reactions

  • Discontinuation due to adverse reactions was observed in 31% of patients treated with Jakafi1
  • The most common adverse reaction leading to treatment discontinuation was infection (10%)1

References

  1. Jakafi Prescribing Information. Wilmington, DE: Incyte Corporation.
  2. Jagasia M, Perales M-A, Schroeder MA, et al. Results from REACH1, a single-cohort phase 2 study of ruxolitinib in combination with corticosteroids for the treatment of steroid-refractory acute graft-vs-host disease. Presented at: 60th American Society of Hematology (ASH) Annual Meeting and Exposition; December 1-4, 2018; San Diego, CA. Abstract 601.
  3. 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 three most common nonhematologic adverse reactions (incidence >10%) were bruising, dizziness and headache. 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 two weeks after the final dose

Please see Full Prescribing Information for Jakafi.