Dosage modification for adverse reactions1
IF AN ADVERSE REACTION (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 BELOW1
*See full Prescribing Information for Warnings and Precautions.
†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 hematological toxicities in CLL/SLL.
‡Evaluate the benefit-risk before resuming treatment.
§For Grade 4 non-hematological toxicities, evaluate the benefit-risk before resuming treatment.
For use with CYP3A inhibitors and inducers, and in patients with hepatic impairment, please see the full Prescribing Information. Consider the risks and benefits of anticoagulant or antiplatelet therapy when co-administered with IMBRUVICA®. Monitor for signs and symptoms of bleeding. Consider the benefit-risk of withholding IMBRUVICA® for at least 3 to 7 days pre- and post-surgery depending upon the type of surgery and risk of bleeding.
Dose modifications for pooled IMBRUVICA®-treated patients
AEs WITH RECOMMENDED DOSE REDUCTIONS FOR POOLED IMBRUVICA®-TREATED PATIENTS (CARDIAC AND NON-CARDIAC RELATED)2*
|AEs with recommended dose reductions per USPI*||Pooled IMB-treated patients|
|Patients with an AE leading to dose reduction, n (%)||21 (9)|
|Outcome of first AE leading to dose reduction, n/N (%)‡,§,|||
|Initial AE eventually resolved||20/21 (95)|
|No recurrence or recurred at lower grade||16/21 (76)|
|Recurred at same or higher grade||5/21 (24)|
|Patients with an AE leading to dose reduction per protocol|
|Patients with any AE leading to dose reduction, n (%)||48 (19)|
Results from this analysis are descriptive in nature and have no implications regarding efficacy.
These pooled analysis results have not been reviewed by the FDA and are not included in Prescribing Information for IMBRUVICA®.
This analysis pooled data from the IMBRUVICA® arm of two multicenter studies of patients with treatment-naive CLL/SLL. RESONATE™-2 included 136 patients who were 65 years or older and received single-agent IMBRUVICA®. iLLUMINATE™ included 113 patients who were 65 years or older or <65 years with coexisting medical conditions and received IMBRUVICA® in combination with obinutuzumab.1
Median (range) follow-up times varied between studies as follows: 86 months (0-97) for RESONATE™-2 and 43 months (0-52) for iLLUMINATE™. Median follow-up was 41 months (range, 0-97 months) for the overall pool.2
Dose modifications were defined in the study protocol; presented with outcomes are only those modified according to current recommendations.
From the USPI
- Adverse reactions leading to dose reduction occurred in approximately 9% of patients.
- 4% to 10% of patients with CLL/SLL receiving IMBRUVICA® discontinued treatment due to adverse reactions.
*AEs for which dose reductions are recommended in the USPI (grade 2 cardiac failure, grade 3 cardiac arrhythmia, grade 3-4 non-hematological AEs [excluding cardiac failure and cardiac arrhythmia], grade 3-4 neutropenia with infection or fever, and grade 4 hematological AEs).
†Denominator is patients with AEs for which dose reductions are recommended in the IMBRUVICA® USPI.
‡Two patients had two different AESIs that led to dose reduction; for one patient, neither recurred, and for the other patient, one did not recur and the other (rash maculo-papular) recurred at a lower grade.
§Five patients had AEs that recurred at the same grade (grade 3 atrial fibrillation [n=1], grade 3 diarrhea [n=1], grade 3 headache [n=1], grade 4 neutropenia [n=1], and grade 3 pleural effusion [n=1]); all resolved without further dose reduction.
Dose modifications for ARs in RESONATE™-2: 8-year dose modification
Median Overall treatment duration
The median duration of IMBRUVICA® treatment was 74 months (range, 0.7-96.6 months; n=135)4,5
Median treatment duration after dose modification*
In a subset of patients who had dose reductions due to adverse reactions (n=31), the median duration of treatment with IMBRUVICA® after the dose modification was 36.1 months (range, 0.0-84+ months)3*
- These data are descriptive in nature only and have no implications regarding efficacy or safety.
- Dose modifications were defined in the study protocol; patients may not have been dose modified according to current recommendations.
- The data described below reflect exposure to IMBRUVICA® in one single-arm, open-label clinical trial (Study 1102) and 5 randomized controlled clinical trials (RESONATE, RESONATE™-2, HELIOS, iLLUMINATE, and E1912) in patients with CLL/SLL (n=2,016 total, including n=1,133 patients exposed to IMBRUVICA®).1
- 4% to 10% patients with CLL/SLL receiving IMBRUVICA® discontinued treatment due to ARs. These included pneumonia, hemorrhage, atrial fibrillation, neutropenia, arthralgia, rash, and thrombocytopenia. ARs leading to dose reduction occurred in approximately 9% of patients.1
*Duration of dose reduction to study drug discontinuation was calculated from first date of the earliest dose reduction to study drug discontinuation.
Dose modifications with adverse reactions can help optimize patient management to enable continued IMBRUVICA® treatment where appropriate.1
AE=adverse event, AR=adverse reaction, CLL=chronic lymphocytic leukemia, FDA=US Food and Drug Administration, IMB=IMBRUVICA®, SLL=small lymphocytic lymphoma.
- IMBRUVICA® (ibrutinib) Prescribing Information.
- Ghia P, Owen C, Barrientos JC, et al. Initiating first-line ibrutinib in patients with chronic lymphocytic leukemia improves overall survival outcomes to rates approximating an age-matched population of ≥65 years. Poster presented at: 64th Annual Meeting of the American Society of Hematology; December 10-13, 2022, New Orleans, LA.
- Data on file.
- Barr PM, Owen C, Robak T, et al. Up to 8-year follow-up from RESONATE-2: first-line ibrutinib treatment for patients with chronic lymphocytic leukemia. Blood Adv. 2022;6(11):3440-3450. doi:10.1182/bloodadvances.2021006434
- Barr PM, Owen C, Robak T, et al. Up to 8-year follow-up from RESONATE-2: first-line ibrutinib treatment for patients with chronic lymphocytic leukemia. Supplemental tables and figures. Blood Adv. 2022;6(11):3440-3450.