Real-world study shows patients treated with Imbruvica were less likely to initiate a next-line treatment than patients on acalabrutinib in first-line chronic lymphocytic leukemia

These data suggest the potential that first-line treatment with Imbruvica in routine practice may provide patients with the ability to use once-daily, all-oral Imbruvica as a monotherapy treatment for a longer period without the need to start the next line of therapy. Data from the study were featured in an oral presentation during the 2022 American Society of Hematology (ASH) Annual Meeting (Abstract #797).

“There are currently no comparative clinical trials in first-line CLL among the BTKi class, highlighting the critical need to leverage real-world experience to support optimized treatment selection,” said Ryan Jacobs†, M.D., Clinical Director, Division of Lymphoma Therapy & Research, Department of Hematologic Oncology, Atrium Health Levine Cancer Institute and principal study investigator. “These results demonstrate the possible impact of using ibrutinib versus acalabrutinib in the front-line setting and provide healthcare professionals with additional data showing differences in time to next treatment.”

The study used Acentrus, de-identified academic electronic medical records (EMR) to identify patients initiating first-line treatment with Imbruvica or acalabrutinib between November 21, 2019 and April 30, 2022 and examined time to next treatment (TTNT) as a clinically meaningful surrogate measure for disease progression. TTNT was defined as the time from the index date to the initiation of a next or additional treatment.

Results showed the following: i. Among treatment-naïve patients with CLL/small lymphocytic leukemia (SLL), patients treated with first-line acalabrutinib (n=373) were 89 percent more likely to start a next treatment than those treated with first-line Imbruvica (n=710) (adjusted hazard ratio [HR] [95 percent confidence interval]: 1.89 (1.12, 3.13); P=0.016). ii. A similar result was observed when censoring anti-CD20 add-on therapy any time after BTK inhibitor treatment (i.e., more than 180 days). iii. At 12 months, 95.3 percent of patients treated with Imbruvica had not initiated a next treatment versus 91.2 percent of patients treated with acalabrutinib. iv. At 15 months, 94.6 percent of patients treated with Imbruvica had not initiated next therapy versus 88.3 percent of patients treated with acalabrutinib.

“Insights from real-world data are becoming more important to help physicians understand optimal treatments and sequencing, especially for patients living with chronic diseases like CLL,” said Imran Khan, M.D., Ph. D., Vice President, Medical Affairs, Oncology, Janssen Biotech, Inc. “With nearly ten years of data since Imbruvica was first approved, we are sourcing real-world data to provide insights from large cohorts of patients further supporting Imbruvica as a first-line treatment option for CLL.”

Additional Study Details: The Acentrus database provides extensive information on medication orders, fills, and administrations. This enables the capture of oral medication use and is unique among available EMR datasets, including Flatiron.

Patients were censored if another BTK inhibitor was initiated at any time, as this may be due to tolerability or non-medical switch rather than disease progression. Other criteria for censored patients were initiation of a second anti-cancer agent in addition to the index BTK inhibitor treatment within 180 days post-index, as this may indicate a first-line combination treatment strategy. The addition of an anti-CD20 antibody or venetoclax after 180 days were considered next treatments. Patients without a next or additional treatment were censored at death or end of data entries.

The median age of patients treated with Imbruvica and acalabrutinib were similar (Imbruvica 73 years [n=710]; acalabrutinib 72 years [n=373]).

Real-World Data Limitations Real world data have the potential to supplement controlled trial data by providing additional information about how a medicine performs across clinical trials and in routine clinical practice. There are limitations, however, and these data cannot be used as stand-alone evidence to validate the efficacy or safety of a treatment. Limitations exist based on EMR data, including potential omissions. However, these would be at random and are expected to have minimal impact on results. Further research is warranted with additional follow-up and larger sample size to inform the evidence gap on the comparative effectiveness of newer BTK inhibitors.