December 10, 2023
By Catlin Nalley
A recent study found that chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) patients who had a dose reduction following an adverse event remained on first-line ibrutinib longer when compared to those who did not have a dose reduction.These findings were recently presented during the 65th American Society of Hematology (ASH) Annual Meeting and Exposition, held December 9-12 in San Diego (Abstract 269).
“Ibrutinib is a once-daily oral BTK inhibitor and is the only targeted therapy to demonstrate significant overall survival benefit in randomized Phase III studies of first-line CLL/SLL,” noted study authorMazyar Shadman, MD, MPH, Associate Professor of the Clinical Research Division at the Fred Hutch Fred Hutchinson Cancer Center in Seattle. “Patients with CLL/SLL who continue treatment with single-agent ibrutinib experience better survival outcomes than those who discontinue treatment within the first 2 years.
“Adverse events may be managed and treatment outcomes can be optimized through ibrutinib dose reduction,” he continued. “We have recent real-world data showing that, in patients with a dose reduction after an adverse event, the time to next treatment (TTNT) is longer compared to the patients who did not have dose reduction after having adverse events.”
In this study, investigators used EMRs from the ConcertAI database to analyze data from previously untreated adults with CLL/SLL. Adverse events were identified based on ICD-9-CM and ICD-10-CM codes, explained Shadman, while noting that casualty cannot be determined.
Study participants were diagnosed with CLL/SLL and treated with 420 mg single-agent ibrutinib on February 12, 2014, or later. Eligible patients had a cardiac or noncardiac adverse event after single-agent ibrutinib initiation without dose reductions/escalations prior to the first AE occurrence (index date).
“Patients were excluded if they received an antineoplastic agent ≤6 months before starting first-line ibrutinib, an antineoplastic agent or combination therapy within 28 days of ibrutinib use, second-line therapy within 30 days of index, hematopoietic stem cell transplant, CYP3A inhibitor during first-line ibrutinib or before start of the second line, an experimental therapy in clinical trials, or if they were diagnosed with other malignancies for which ibrutinib is indicated within 6 months prior to ibrutinib initiation,” according to the study authors.
Outcomes described following adverse event occurrence included demographics, clinical characteristics, treatment patterns, and TTNT. Researchers defined a dose reduction as a “dose lower than 420 mg per day on or after the date of first AE post-ibrutinib initiation, per pharmacy records.”
Of the 522 patients included in the study, there were 427 patients without a dose reduction and 95 with a dose reduction. Data showed that patients with a dose reduction were slightly older than those without a dose reduction. Generally, the baseline and demographic characteristics were well-balanced between the two patient groups.
Shadman reported that the median time between ibrutinib initiation and the end of first-line ibrutinib treatment was significantly longer among patients with a dose reduction compared with those without a dose reduction.
“Among patients with and without a dose reduction, the median time from ibrutinib initiation to the first incident adverse event was 37 days and 65 days, respectively,” he noted, while also reporting that 27 percent of patients with a dose reduction resumed the full ibrutinib dose of 420 mg per day after dose reduction.
Additionally, fewer patients with a dose reduction had a next treatment (46%) when compared with those without a dose reduction (54%). Median TTNT was significantly longer in patients with a dose reduction, according to the data.
In the adjusted analysis, Shadman and colleagues found that patients with a dose reduction had a 41 percent reduction in the risk of starting a subsequent therapy or death when compared to those without a dose reduction.
When looking at health resource utilization, the study authors observed that patients who underwent a dose reduction had significantly lower outpatient visits per patient per month.
“Overall, among patients with CLL or SLL who received ibrutinib at first-line, those patients with dose reduction after having an adverse event remained on first-line therapy with ibrutinib longer than those who did not have dose reduction,” Shadman said while summarizing his presentation.
“Ibrutinib dose reductions may offer patients an opportunity to achieve an optimal outcome by enabling them to maintain or remain on therapy for a longer time,” he concluded. “Patients with ibrutinib dose reduction used less health care resources in the outpatient setting than those without dose reduction.”
Catlin Nalley is a contributing writer.