ORRs in patients with steroid-refractory cGVHD across therapies1

REACH3: ORRs at Week 24 With Jakafi® (ruxolitinib) and Individual BATs1

Jakafi® (ruxolitinib) vs best available therapies bar chart
  • REACH3 was not powered to compare ORR for Jakafi to individual BATs
  • 74% of patients on BAT received ECP, MMF, or ibrutinib1*

*BAT was chosen by the investigator at the time of randomization.2

Dr Chaudhary

[Another primary goal] is to help prevent disease progression by keeping patients on an effective therapy for ongoing response to treatment. This is why we again turn to Jakafi. While we assess the benefits of treatment versus the risks in each patient, we believe that intervening early with Jakafi is important.

Preet M. Chaudhary, MD, PhD, GVHD Expert

REACH3 primary endpoint

REACH3 Primary Endpoint: ORR at Week 241,a

REACH3 Primary endpoint bar chart

ORR Through Week 242,c

ORR through week 24 bar chart

aORR was defined as the proportion of patients with CR or PR at week 24, according to 2014 NIH consensus criteria.1

bOne-sided P value, OR, and 95% CI were calculated using stratified Cochran-Mantel-Haenszel test, stratifying for moderate and severe cGVHD.1

cDefined 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 treated with Jakafi were

3×

more likely to achieve an overall response at week 24 vs BAT (OR, 2.99)1

Median time to first response

3

weeks (range: 2-24) with Jakafi and 4 weeks (range: 2-25) with BAT2

  • 74% of patients treated with BAT received ECP, MMF, or ibrutinib; ORR at week 24 was1*†:
    • ECP: 29.1% (16/55; CR, 1.8%; PR, 27.3%), MMF: 28.6% (10/35; CR, 2.9%; PR, 25.7%), ibrutinib: 22.2% (6/27; CR, 7.4%; PR, 14.8%)3

*The 74% value is based on the number of patients treated with BAT (n=158). ORRs for the remaining BATs were 20% (1/5) for everolimus, 25% (2/8) for imatinib, 20% (1/5) for infliximab, 30% (3/10) for low-dose MTX, 16.7% (1/6) for rituximab, and 28.6% (2/7) for sirolimus.1,3

†REACH3 was not powered to compare ORR for Jakafi to individual BATs.

BAT=best available therapy; cGVHD=chronic graft-versus-host disease; CI=confidence interval; CR=complete 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.

Study design

REACH3 Study Design1,2

REACH3 Study design graphic
  • Inclusion criteria1*
    • Age 12 and older
    • Allogeneic stem cell transplant from any donor source and donor type
    • SR/SD cGVHD per NIH consensus criteria (moderate or severe)
    • Evident myeloid and platelet engraftment
  • In the Jakafi Prescribing Information, efficacy was based on ORR through week 24 (cycle 7, day 1)2

*Organ involvement at baseline for all patients (N=329): skin (71.1%), mouth (60.8%), eyes (57.4%), lungs (42.9%), joints and fascia (27.4%), liver (24.9%), GI tract (22.8%), genital tract (9.4%), missing (0.3%). Organ involvement was based on NIH consensus staging criteria at screening. A score of ≥1 was counted as organ involvement. Patients with missing assessments of single organs were counted as having no organ involvement for the organ assessed.1

aCrossover 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. 61 patients crossed over to Jakafi after week 24. 72% of those who crossed over remained on Jakafi longer than 24 weeks.1,4

bBAT was chosen by the investigator prior to randomization: Options included ibrutinib, ECP, low-dose MTX, MMF, rituximab, everolimus, sirolimus, imatinib, infliximab, and pentostatin.2

cDefined as the proportion of patients with CR or PR at week 24.1

dDefined as the earliest time from date of randomization to relapse or recurrence of underlying disease or death due to underlying disease, nonrelapse mortality, or addition or initiation of another systemic therapy for cGVHD.1

eDefined as a ≥7-point reduction from baseline in total symptom score on the mLSS, which measures the symptoms of cGVHD on a scale of 0 to 100, with higher scores indicating worse symptoms.1

BAT=best available therapy; BID=twice daily; cGVHD=chronic graft-versus-host disease; CNI=calcineurin inhibitor; CR=complete response; ECP=extracorporeal photopheresis; FFS=failure-free survival; GI=gastrointestinal; mLSS=modified Lee Symptom Scale; MMF=mycophenolate mofetil; MTX=methotrexate; NIH=National Institutes of Health; ORR=overall response rate; PR=partial response; REACH=Ruxolitinib in patiEnts with refrACtory graft-versus-Host disease after allogeneic stem cell transplantation; SD=steroid-dependent; SR=steroid-refractory.

SEE RESULTS TREATING MODERATE VS SEVERE cGVHD SEE RESPONSE ACROSS ORGANS SEE FFS

BAT=best available therapy; cGVHD=chronic graft-versus-host disease; CR=complete response; ECP=extracorporeal photopheresis; FFS=failure-free survival; MMF=mycophenolate mofetil; MTX=methotrexate; ORR=overall response rate; PR=partial response; REACH=Ruxolitinib in patiEnts with refrACtory graft-versus-Host disease after allogeneic stem cell transplantation.

References: 1. 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. 2. Jakafi [package insert]. Wilmington, DE: lncyte Corporation. 3. Locatelli F; for the REACH3 Study Group. Ruxolitinib vs best available therapy in patients with steroid-refractory/dependent chronic graft-vs-host disease: subgroup analyses of overall response rate in the phase 3 REACH3 trial. Presented at: 47th Annual Meeting of the EBMT; March 14-17. 2021; Rome, Italy. 4. Data on file. Incyte Corporation. Wilmington, DE.

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Indications and Usage

Jakafi® (ruxolitinib) 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 (aGVHD) in adult and pediatric patients 12 years and older.

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.

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.

Indications and Usage

Jakafi® (ruxolitinib) 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 (aGVHD) in adult and pediatric patients 12 years and older.

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.

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.