Real-World Study Shows Patients Treated with IMBRUVICA® (ibrutinib) Were Less Likely to Initiate a Next-Line Treatment than Patients on Acalabrutinib in First-line Chronic Lymphocytic Leukemia

The Janssen Pharmaceutical Companies of Johnson & Johnson announced results of a real-world study showing that patients with chronic lymphocytic leukemia (CLL) treated with first-line acalabrutinib monotherapy were 89 percent more likely to start a next-line treatment than those treated with IMBRUVICA^® (ibrutinib). 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.

“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:

• 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).
• A similar result was observed when censoring anti-CD20 add-on therapy any time after BTK inhibitor treatment (i.e., more than 180 days).
• 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.
• 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.

About IMBRUVICA^®
IMBRUVICA^® (ibrutinib) is a once-daily oral medication that is jointly developed and commercialized by Janssen Biotech, Inc. and Pharmacyclics LLC, an AbbVie company. IMBRUVICA^® blocks the Bruton’s tyrosine kinase (BTK) protein, which is needed by normal and abnormal B cells, including specific cancer cells, to multiply and spread. By blocking BTK, IMBRUVICA^® may help move abnormal B cells out of their nourishing environments and inhibits their proliferation.

IMBRUVICA^® is approved in more than 100 countries and has been used to treat more than 270,000 patients worldwide. There are more than 50 company-sponsored clinical trials, including 18 Phase 3 studies, more than 11 years evaluating the efficacy and safety of IMBRUVICA^®.

IMBRUVICA^® was first approved by the U.S. Food and Drug Administration (FDA) in November 2013 and today is indicated for adult patients in six disease areas, including five hematologic cancers. These include indications to treat adults with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) with or without 17p deletion (del17p), adults with Waldenström’s macroglobulinemia (WM), adult patients with previously treated mantle cell lymphoma (MCL)*, as well as to treat adult patients with previously treated marginal zone lymphoma (MZL) who require systemic therapy and have received at least one prior anti-CD20-based therapy*, and adult and pediatric patients aged one year and older with previously treated chronic graft-versus-host disease (cGVHD) after failure of one or more lines of systemic therapy.

*Accelerated approval was granted for MCL and MZL based on overall response rate. Continued approval for MCL and MZL may be contingent upon verification and description of clinical benefit in confirmatory trials.

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Related Topics and Keywords

chronic lymphocytic leukemia, ibrutinib, IMBRUVICA®, Johnson and Johnson