Jakafi is the first and only dual-pathway treatment for
nAMD, DME, and RVO1†
of patients are covered to start JAKAFI® (faricimab-svoa) as their first branded treatment*
The ques and disease management related to chronic graft-versus host disease (cGVHD). Your participation instions throughout this patient case are designed to help gain a better understanding of treatment strategie these questions is invaluable, as the insights you provide can help enhance the management of cGVHD patients.
For each response per unique participant, PRI Healthcare Solutions will donate $25 (up to a total of $15,000) to The Meredith A. Cowden Foundation.
Patient Characteristics
- 51 year-old male
- Past medical history of AML with FLT3 mutation treated with standard induction chemotherapy, consolidation with busulfan plus fludarabine and allo-HSCT from a matched unrelated donor
- Initial immunosuppressive regimen of tacrolimus/methotrexate (TAC/MTX)
- Repeat bone marrow biopsy after transplant showed hematological and morphological remission
allo-HSCT=allogeneic hematopoietic stem cell transplantation; AML=acute myeloid leukemia; FLT3=FMS-like tyrosine kinase 3; GVHD=graft-versus-host disease.
Following day 100, I encourage my transplant patients to report any new or changing symptoms:
- A Within 1-2 days of occurrence
- B Within 1 week of occurrence
- C Within 2 weeks of occurrence
- D The next time they return for an appointment
5-Month Follow-Up Post Transplant: Chronic GVHD Diagnosis
- Patient is currently on decreasing TAC taper and also receiving antimicrobial prophylaxis and acyclovir
- On examination, has a maculopapular rash across both upper limbs and chest and oral lesions suggestive of lichen planus
- Patient reports symptoms began 3-4 months post allo-HSCT and was unsuccessful in managing with OTCH solutions
- During the visit, patient is noticeably rubbing their eyes a lot – he says his eyes have been feeling dry but not so much as to affect his daily activities
- According to the NIH global severity score of chronic GVHD, confirmed diagnosis of moderate chronic GVHD (based on skin score 2, mouth score 1)
OTCH=over-the-counter health.
In adult and pediatric patients 12 years and older with cGVHD1
INTERVENE WITH JAKAFI
at the first sign of initial systemic treatment failure
Jakafi®(ruxolitinib) is indicated for treatment of chronic graft-versus-host disease (GVHD) after failure of one or two lines of systemic therapy in adult and pediatric patients 12 years and older.
Patients were 3x more likely to have an overall response with Jakafi vs BAT2
REACH3 Primary Endpoint: ORR at Week 242,a
ORR Through Week 241,c
In the Jakafi Prescribing Information, efficacy was based on ORR through week 24 (cycle 7, day 1)1
If I don't see at least some response within the first week or I am unable to taper steroid use, I intervene with Jakafi as opposed to taking the chance that the disease could become more severe.
Karolina Faysman, MSN, AOCNP
GVHD Expert
REACH3 was a randomized, open-label, multicenter, phase 3 study of Jakafi vs BAT in patients with steroid-refractory (SR) cGVHD (N=329).1,2 The starting dose for Jakafi was 10 mg BID. Crossover 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.2 Patients included in the study were 12 years and older, had undergone allogeneic hematopoietic stem cell transplant from any donor source/type, and had evident myeloid and platelet engraftment.1,2 BATs included ibrutinib, extracorporeal photopheresis, low-dose methotrexate, mycophenolate mofetil, rituximab, everolimus, sirolimus, imatinib, infliximab, or pentostatin.1 REACH3 followed NIH criteria for steroid refractory and steroid dependent.2 SR disease was defined as lack of response or disease progression after ≥1 week of prednisone 1 mg/kg/day, disease persistence without improvement after ≥4 weeks of prednisone 0.5 mg/kg/day or 1 mg/kg every other day, or increase in prednisone dose to >0.25 mg/kg/day after 2 unsuccessful attempts to taper the dose.2,3
aORR was defined as the proportion of patients with CR or PR at week 24, according to 2014 NIH consensus criteria.2
bOne-sided P value, OR, and 95% CI were calculated using stratified Cochran-Mantel-Haenszel test, stratifying for moderate and severe cGVHD.2
cDefined as the proportion of patients who achieved CR or PR through week 24 (cycle 7, day 1), according to 2014 NIH consensus criteria.1
BAT=best available therapy; BID=twice daily; CI=confidence interval; CR=complete response; OR=odds ratio; ORR=overall response rate; PR=partial response.
Overall response rates were superior with Jakafi vs BAT, regardless of organs involved2
REACH3 Subgroup Analysis: ORR at Week 24 by Baseline Organ Involvement2,a
aPatients with >1 affected organ were counted in each organ subgroup. Organ involvement was defined as organ score ≥1 based on the cGVHD staging criteria.2
GI=gastrointestinal.
In practice, we monitor skin disease as a surrogate for disease progression—as GVHD is a systemic disease—and take an assertive approach with Jakafi treatment to help halt that progression.
Preet M. Chaudhary, MD, PhD,
GVHD Expert
Final analysis of REACH3 data
Jakafi demonstrated higher probability of maintaining response: 59.6% at 3 years vs 26.7% with BAT3,5*
Kaplan-Meier Analysis of DOR3,5
In the primary analysis, estimated probability of maintaining response to therapy at 12 months was 68.5% with Jakafi (95% CI: 58.9-76.3) and 40.3% with BAT (95% CI: 30.3-50.2)2
Estimated probability of maintaining DOR
At 12 months:
70.2%with Jakafi (95% CI, 61.4-77.5) vs 39.8% with BAT (95% CI, 30.4-49.1)3,5
At 36 months:
59.6%with Jakafi (95% CI: 50.4-67.6) vs 26.7% with BAT (95% CI, 18.5-35.5)3,5
Median DOR was not reached with Jakafi vs 6.4 months with BAT5
Patients who crossed over from BAT to Jakafi still had significant response rates. Additionally, after crossover, disease progression occurred in only 1 patient5
*DOR was defined as the time from first response until cGVHD progression, death, or the date of change/addition of systemic therapies for cGVHD.3
Jakafi adverse reactions
Most Frequent Adverse Reactions (Occurring in ≥10% of Patients) up to Week 24 (Cycle 7, Day 1)1,a
| Adverse Reactions | Jakafi (n=165) | BAT (n=158) | ||
|---|---|---|---|---|
| All Grades, b% | Grade ≥3, % | All Grades, b% | Grade ≥3, % | |
| Infections (pathogen not specified) | 45 | 15 | 44 | 16 |
| Viral infections | 28 | 5 | 23 | 5 |
| Musculoskeletal pain | 18 | 1 | 13 | 0 |
| Hypertension | 16 | 5 | 13 | 7 |
| Pyrexia | 16 | 2 | 9 | 1 |
| Cough | 13 | 0 | 8 | 0 |
| Fatigue | 13 | 1 | 10 | 2 |
| Hemorrhage | 12 | 2 | 15 | 2 |
| Nausea | 12 | 0 | 13 | 2 |
| Dyspnea | 11 | 1 | 8 | 1 |
| Edema | 10 | 1 | 12 | 1 |
| Diarrhea | 10 | 1 | 13 | 1 |
aSafety population: all patients who received ≥1 dose of study treatment.2
bInfections were classified by type at the investigator’s discretion by using an infection-specific grading system predictive of mortality that was developed for and validated in allogeneic stem cell transplant recipients based on the criteria provided in the protocol.2
In a 3-year final analysis,Jakafi was well tolerated with no unexpected toxicities and safety that was consistent with earlier studies5
References:
- Jakafi [package insert]. Wilmington, DE: lncyte Corporation.
- 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/NEJMoa.
- Data on file. Incyte Corporation. Wilmington, DE.
- Zeiser R, Xue Z, Bhatt V, Galvin J, Locatelli F. Early versus late treatment with ruxolitinib in patients with steroid-refractory chronic graft-versus-host disease: a post hoc analysis from the randomized, phase 3 REACH3 study. Poster presented at: 64th American Society of Hematology (ASH) Annual Meeting and Exposition; December 10-13, 2022; New Orleans, LA.
- Zeiser R, Russo D, Ram R, et al. Ruxolitinib in patients with chronic graft-versus-host disease: 3-year final analysis of efficacy and safety from the phase III REACH3 study. Presented at: 65th American Society of Hematology Annual Meeting and Exposition; December 9-12, 2023; San Diego, CA. Session 722.
INDICATION AND USAGE
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 x 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
- 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.