Nurse Management of cGVHD in Patients on Ibrutinib Focuses on Education

Melissa Logue, ANP-BC, of Vanderbilt University Medical Center in Nashville, TN, and coauthors presented information on ibrutinib and discussed ways oncology nurses can guide patient care and education on managing cGVHD symptoms while on ibrutinib during a poster session at the 43rd Annual Congress in Washington, DC (http://epostersonline.com/ons2018/node/2460). The poster was titled “Nurse Management of Patients Receiving Ibrutinib for Steroid-Dependent/Refractory Chronic Graft-Versus-Host Disease.”

The objective of this multicenter, phase Ib, open-label study was to evaluate nursing practice patterns in managing symptom burden, treatment-emergent adverse events (TEAEs), and concomitant medications in patients receiving ibrutinib for cGVHD after failing at least one prior regimen. A total of 42 patients with a median age of 56 years (range = 19–74 years) who had three or more prior regimens for cGVHD received ibrutinib dosed at 420 mg/day until disease progression or intolerable toxicity. Patients and providers used an online messaging system and study visit forms to manage AEs and concomitant medications.

Patients received ibrutinib for a median of 4.4 months (range = 0.2–24.9 months). Researchers reported that most patients (88%) had cGVHD with multiple organs involved, including mouth (86%), skin (81%), gastrointestinal system (33%), and liver (17%).

A total of 28 of the 42 patients were considered responders. Study results showed that 32% of responders (n = 9) had a complete response, and the rate of sustained response for at least 20 weeks was 71% (n = 20). Of the total 42 patients, 62% (n = 26) achieved corticosteroid doses of less than 0.15 mg/kg per day by week 52 while on ibrutinib.

Nurse Management of Adverse Events and Medications

Oncology nursing management of TEAEs and concomitant medications requires ongoing communication between healthcare providers and patients. Oncology nurses can use education to guide patients on ways to manage their cGVHD symptoms while on ibrutinib treatment, including AEs (see Table 1).

Nurses also need to guide patient education on concomitant medications, including cytochrome P450 (CYP) 3A inhibitors (see Table 2), anticoagulants, and antiplatelet drugs. The 42 patients in the study were taking a median of 13 concomitant medications within the first 10 days of study drug administration, including prednisone (100%), trimethoprim/sulfamethoxazole (79%), acyclovir (71%), and oxycodone (45%).

Table 1. Management of Adverse Events in Patients With cGVHD Taking Ibrutinib

Adverse Eventa	Ibrutinib U.S. Prescribing Information (USPI)	Nursing Best Practicesb
Fatigue	Interrupt ibrutinib therapy if AE is grade 3 or higher Once AE resolves to grade 1 or baseline (recovery), reinitiate ibrutinib at starting dose (420 mg) If AE reoccurs, reduce dose by 140 mg/day, with a second reduction (140 mg/day) if needed Discontinue after two dose reductions if AE persists or recurs	Increase exercise routines Take ibrutinib at bedtime
Diarrhea	Antidiarrheals for drug-related diarrhea (i.e., not related to infection)
Muscle spasms	Physical therapy Stretching Increase electrolytes (e.g., potassium, magnesium) as much as possible
Pneumonia	Prophylaxis according to standard of care Monitor and evaluate for fever and infections; treat appropriately	Increase activity Pulmonary exercises Prophylactic medications Treat/prevent pneumococcal pneumonia with pneumococcus vaccinations, penicillin, erythromycin Treat/prevent pneumocystis pneumonia (fungal pneumonia) with trimethoprim/sulfamethoxazole, dapsone, pentamidine, atovaquone

^a Experienced by at least 20% of patients with cGVHD as listed in the ibrutinib USPI

^b Institutional guidelines from Vanderbilt University Medical Center in Nashville, TN, and Dana Farber Cancer Institute in Boston, MA

Table 2. Management With Concomitant CYP3A Inhibitors

Concomitant CYP3A Inhibitors	USPI Recommended Ibrutinib Dose Adjustment	Oncology Nursing Patient Education
Moderate CYP3A inhibitor	420 mg once daily or modify dose based on AE profile as recommended	Instruction on medication schedule Communicate with clinical pharmacists/study nurses Taper off prior to enrollment Adjust doses based on drug interactions Perform additional education and patient teaching Managing concomitant medications and drug interactions Avoid any foods that may interfere with systemic ibrutinib levels (e.g., grapefruit juice) Possible interactions of any new medications Remind patients to discuss any other medications with their physician to address potential drug interactions
Voriconazole 200 mg twice daily Posaconazole suspension 100 mg once daily or 100 mg twice daily or 200 mg twice daily	280 mg once daily or modify dose based on AE profile as recommended
Posaconazole suspension 200 mg 3 times daily or 400mg 2 times daily or IV injection 300 mg once daily or delayed-release tablets 300 mg once daily	140 mg once daily or interrupt dose based on AE profile as recommended
Other strong CYP3A inhibitors	AVOID concomitant use or interrupt ibrutinib if inhibitors such as anti-infectives will be used ≤7 days; after discontinuation of a CYP3A inhibitor, resume previous dose of ibrutinib
Concomitant Corticosteroids and Immunosuppressants	Clinical Study Experience (Miklos 2017)
Prednisone Tacrolimus Cyclosporine A Mycophenolate mofetil Sirolimus	Taper as clinically indicated