FOR THE FIRST TIME EVER1
APPROVED IN AUGUST 2022
IMBRUVICA® SAFETY AND EFFECTIVENESS HAVE BEEN ESTABLISHED FOR CHILDREN AS YOUNG AS 1 YEAR OF AGE WITH PREVIOUSLY TREATED cGVHD2*
*This indication is supported by evidence from the iMAGINE study
cGVHD TREATMENT
AVAILABLE AS AN ORAL
SUSPENSION FOR CHILDREN
Pediatric patients under the age of 12 with cGVHD and have failed one or more lines of systemic therapy have limited treatment options1
Data from the iMAGINE trial support that IMBRUVICA® produced a clinically meaningful response in pediatric patients with previously treated cGVHD2
cGVHD
Indication2
IMBRUVICA® is indicated for the treatment of adult and pediatric patients age 1 year and older with chronic graft versus host disease (cGVHD) after failure of one or more lines of systemic therapy.
Study design: iMAGINE trial2,3
An open-label, multicenter, single-arm, phase 1/2 study consisting of 47 patients aged
1 to <22 years with previously treated moderate or severe cGVHD.
Select Inclusion Criteria
- Platelets ≥30 × 109/L and no transfusion for 7 days
- Absolute neutrophil count ≥1.0 × 109/L and off growth factor support for 7 days
- Total bilirubin ≤1.5× ULN (unless of non-hepatic origin or due to Gilbert's syndrome) or ≤3.0 x ULN if due to GVHD
- Estimated creatinine clearance ≥30 mL/min
Select Exclusion Criteria
- Single-organ genitourinary involvement was the only manifestation of cGVHD
ULN=upper limit of normal.
Select Patient Demographics:
- Median age of patients was 13 years (range: 1-19)
- Median time since diagnosis was 16.1 months
- Median number of prior cGVHD treatments was 2 (range: 1-12)
- Daily corticosteroid dose (prednisone or prednisone equivalent) at baseline was 0.47 mg/kg/day
Study Design Dosing:
- Patients 12 years of age and older (n=26): 420 mg taken orally once daily until disease progression.
- Patients 1 to less than 12 years of age (n=21): starting dose of 120 mg/m2, after 14 days of treatment 240 mg/m2 taken orally once daily (up to a dose of 420 mg)
Efficacy in children aged 1 to <22 years with cGVHD who have failed one or more lines of therapy2
Approximately 6 out of 10 patients responded to treatment with IMBRUVICA® based on ORR
The efficacy of IMBRUVICA® was established based on responses evaluated through Week 25 where overall response included complete response or partial response according to the 2014 National Institutes of Health Consensus Development Project Response Criteria.
*Skin, mouth, liver, upper and lower GI, esophagus, lung, eye, and joint/fascia were the organs/sites considered in evaluating overall response.
CI=confidence interval, CR=complete response, ORR=overall response rate, PR=partial response.
Time to response/duration of response2
Time to first response
Median time to first response was 0.9 month (range: 0.9, 6.1)
The median time from first response to death or new systemic therapies for cGVHD was 14.8 months (95% CI: 4.6, not evaluable).
Median duration of response
*Median duration of response was calculated from first response to progression, death, or new systemic therapy for chronic GVHD.
Improvement in patient-reported symptom bother2
ORR results were supported by exploratory analyses of patient-reported symptom bother, which showed at least a 7-point decrease in Lee Symptom Scale overall summary score through Week 25 in 50% of patients age 12 years and older†
†The Lee Symptom Scale assesses the severity of cGVHD by directly measuring patient symptom burden based on manifestations of the disease (skin, energy, lung, nutritional status, psychological functioning, eye, and mouth)4.
Safety in pediatric patients with cGVHD who have failed one or more lines of therapy2
The iMAGINE trial safety
Median duration of exposure was 7.1 months (range: 0.2, 25.9 months)2
Adverse reactions reported in ≥10% of patients aged 1 to <22 years
with cGVHD in iMAGINE2
*Includes multiple ADR terms.
†Includes 1 event with a fatal outcome.
ADR=adverse drug reaction.
Select hematologic laboratory abnormalities (≥10%) that worsened from baseline in patients who received IMBRUVICA® in the iMAGINE trial2
Treatment-emergent Grade 4 neutropenia occurred in 3% of patients.
23% of previously treated pediatric and young adult (aged 1 to <22 years) patients who received IMBRUVICA® in the iMAGINE study discontinued treatment due to adverse reactions2
- Adverse reactions which resulted in permanent discontinuation in at least 2 patients included hemorrhage
- Adverse reactions leading to dose reduction occurred in 19% of patients
- Adverse reactions which required dose reduction in at least two patients included stomatitis.
The safety and effectiveness of IMBRUVICA® in pediatric patients for indications other than cGVHD have not been established.
Please see the downloadable cGVHD brochure for safety, efficacy, dosing, and trial information.
download
IMBRUVICA® is available as a once-daily oral suspension for children aged 1 to <12 years and as capsules or tablets2
- 240 mg/m2 administered orally once daily (up to a maximum daily dose of 420 mg) until cGVHD progression, recurrence of an underlying malignancy, or unacceptable toxicity
- When a patient no longer requires therapy for the treatment of cGVHD, IMBRUVICA® should be discontinued considering the medical assessment of the individual patient
- 420 mg administered orally once daily until cGVHD progression, recurrence of an underlying malignancy, or unacceptable toxicity
- IMBRUVICA® can be dosed as a single 420-mg tablet or three 140-mg capsules
- When a patient no longer requires therapy for the treatment of cGVHD, IMBRUVICA® should be discontinued considering the medical assessment of the individual patient
See full Prescribing Information for complete dosage and administration details.
See full Prescribing Information for complete dosage and administration details.
*BSA = body surface area.
Please see full Prescribing Information for volume of IMBRUVICA® needed to reach the recommended dosage.
- The coadministration of IMBRUVICA® with a strong or moderate CYP3A inhibitor may increase ibrutinib plasma concentrations. Increased ibrutinib concentrations may increase the risk of drug-related toxicity
- After discontinuation of a CYP3A inhibitor, resume previous dose of IMBRUVICA®
- Avoid grapefruit and Seville oranges during IMBRUVICA® treatment, as these contain strong or moderate inhibitors of CYP3A
Administer IMBRUVICA® at approximately the same time each day. Swallow tablets or capsules whole with a glass of water. Do not open, break, or chew the capsules. Do not cut, crush, or chew the tablets. Follow Instructions for Use for further administration details of IMBRUVICA® oral suspension. If a dose of IMBRUVICA® is not taken at the scheduled time, it can be taken as soon as possible on the same day with a return to the normal dosing schedule the following day. Do not take extra doses of IMBRUVICA® to make up for the missed dose2.
Dose Modifications for Adverse Reactions in cGVHD
Dosage modifications for adverse reactions in cGVHD
If an AR listed below occurs, interrupt IMBRUVICA® therapy at each occurrence of the same AR. Once the AR has improved to Grade 1 or baseline, follow the recommended dosage modifications below2
*Please see Warnings and Precautions section of the Prescribing Information
†Grading based on National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) criteria, or International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria for hematologic toxicities in CLL/SLL.
‡Evaluate the benefit-risk before resuming treatment.
§For Grade 4 non-hematologic toxicities, evaluate the benefit-risk before resuming treatment.
Refer to Dosage and Administration (2.2) Table 3 in the Prescribing Information for recommended dosage modifications based on BSA using either IMBRUVICA® capsules/tablets or oral suspension.
Patients on CYP3A Inhibitors
Patients on CYP3A inhibitors may receive IMBRUVICA®2
In an observational, analytical, retrospective cohort study,
*BSA = body surface area.
†Modify dose as recommended.
Refer to Dosage and Administration (2.2) Table 3 in the Prescribing Information for recommended dosage modifications based on BSA using either IMBRUVICA® capsules/tablets or oral suspension.
Please see full Prescribing Information for volume of IMBRUVICA® needed to reach the recommended dosage.
- The coadministration of IMBRUVICA® with a strong or moderate CYP3A inhibitor may increase ibrutinib plasma concentrations. Increased ibrutinib concentrations may increase the risk of drug-related toxicity
- After discontinuation of a CYP3A inhibitor, resume previous dose of IMBRUVICA®
- Avoid grapefruit and Seville oranges during IMBRUVICA® treatment, as these contain strong or moderate inhibitors of CYP3A
Patients with hepatic impairment
Dosage modifications for use in hepatic impairment
- The recommended dosage is 140 mg daily for patients 12 years of age and older with total bilirubin level >1.5 to 3x upper limit of normal (ULN) (unless of non-hepatic origin or due to Gilbert’s syndrome)
- The recommended dosage is 80 mg/m2 daily for patients 1 to less than 12 years of age with total bilirubin level >1.5 to 3x ULN (unless of non-hepatic origin or due to Gilbert’s syndrome)
- Avoid the use of IMBRUVICA® in these patients with total bilirubin level >3x ULN (unless of non-hepatic origin or due to Gilbert’s syndrome)
Oral Suspension and Administration of Oral suspension
Administration of IMBRUVICA® oral suspension for patients aged 1 to <12 years2
Click here to learn more about the IMBRUVICA® By Your Side patient support program
Click here to see NDC numbers for IMBRUVICA® dosing
Click here to see IMBRUVICA® Diagnosis Codes
CR=complete response, DOR=duration of response, NE=not estimable, ORR=overall response rate, PR=partial response.
References: 1. National Comprehensive Cancer Network. Hematopoietic Cell Transplantation (Version 1.2022). 2. IMBRUVICA® (ibrutinib) Prescribing Information. 3. Data on file. 4. Lee S, Cook EF, Soiffer R, et al. Development and validation of a scale to measure symptoms of chronic graft-versus-host disease. Biol Blood Marrow Transplant. 2002;8(8):444–452. 5. Perez P, Patiño J, Franco AA. Prophylaxis for invasive fungal infection in pediatric patients with allogeneic hematopoietic stem cell transplantation. Blood Res. 2022;57:34-40.