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ASCO 2015: New Ibrutinib Combination Regimen Shows Substantial Benefits in Relapsed Chronic Lymphocytic Leukemia

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Key Points

  • Patients with chronic lymphocytic leukemia that progressed despite prior therapy had an 80% lower risk of disease progression or death if they received ibrutinib and bendamustine/rituximab rather than placebo and bendamustine/rituximab.
  • Based on this benefit, patients were permitted to cross over to the ibrutinib group, and even with 90 patients crossing over to receive ibrutinib at the time of disease progression, there was a 37% decrease in the risk of death.
  • Response rates were significantly higher in the ibrutinib group than in the placebo group (82.7% vs 67.8%).

First results from a randomized phase III study show that the combination of ibrutinib (Imbruvica) and bendamustine (Treanda)/rituximab (Rituxan) improves outcomes for patients with chronic lymphocytic leukemia (CLL) that progressed despite prior therapy. At a median follow-up of 17 months, patients who received ibrutinib and bendamustine/rituximab had an 80% lower risk of disease progression or death than those who received placebo and bendamustine/rituximab.

Based on this striking benefit, patients were permitted to cross over from the placebo group to receive ibrutinib. At the time of the interim analysis, 90 patients (31%) from the placebo group had already crossed over to the ibrutinib group.

“This was one of the most rigorous clinical trials ever conducted in CLL and it truly validates ibrutinib as an important drug for this cancer,” said lead study author Asher Chanan-Khan, MD, Professor of Medicine at Mayo Clinic in Jacksonville, Florida. “We found that ibrutinib can be safely paired with existing therapy to powerfully prolong remissions and improve patients’ well-being.”

Dr. Chanan-Khan discussed the study and its implications at a press conference at the 2015 ASCO Annual Meeting and later at the oral session on leukemia, myelodysplasia, and transplantation (Abstract LBA7005).

Significantly Higher Response Rates

In the study, 578 patients with previously treated CLL were randomly assigned 1:1 to treatment with ibrutinib and bendamustine/rituximab or placebo and bendamustine/rituximab. The median age of the patients was 64, and the median number of prior therapies was two.

After an average follow-up of 17.2 months, the median progression-free survival was 13.3 months in the placebo group and was not reached in the ibrutinib group. The hazard ratio was 0.20, “which translates into a reduced risk of progressions by 80%, and this is remarkable,” Dr. Chanan-Khan said at the press conference.

Response rates were significantly higher in the ibrutinib group than in the placebo group (82.7% vs 67.8%). Patients with disease-related fatigue had greater and more rapid improvement if they took ibrutinib.

“The overall impact of the bendamustine/rituximab and ibrutinib combination was a 37% decrease in the risk of death, and this was noted despite the fact that 90 patients crossed over to receive ibrutinib at the time of progression,” Dr. Chanan-Khan reported.

The rates and types of side effects were comparable between the two treatment groups. The most frequent side effects were neutropenia, affecting more than 50%, and nausea, affecting more than 35%.

Dr. Chanan-Khan concluded that the “remarkable improvement” in overall response rate and “impressive decrease in the risk of progression and death” represent a “changing point in the history of CLL, where the treatment of CLL patients will no longer be bendamustine/rituximab, but bendamustine/rituximab with ibrutinib.”

Next Steps in Ibrutinib Research

Ibrutinib is a first-in-class oral once-daily targeted treatment that blocks Bruton’s tyrosine kinase. The drug was approved by the U.S. Food and Drug Administration last year for the treatment of patients with CLL who have received at least one prior therapy, and ibrutinib studies were highlighted at the last year’s ASCO Annual Meeting.

“Progress against chronic lymphocytic leukemia was one of the most important themes of the last two years, and now we have yet another potent treatment approach for patients who have exhausted other options. These results suggest that we can achieve better outcomes for patients by pairing novel therapies with established treatments,” stated ASCO expert Merry-Jennifer Markham, MD. Dr. Markham is an Assistant Professor in the Division of Hematology and Oncology at the University of Florida, Gainesville.

The next steps for this area of research include evaluating ibrutinib as a single agent and in combination with drugs targeting the CD20 protein in patients with newly diagnosed, symptomatic, and asymptomatic CLL.

This study received funding from Janssen Research & Development, LLC (Janssen). For full disclosures of the study authors, view the study abstract at abstract.asco.org.

Watch The ASCO Post Newsreels for an interview with Dr. Chanan-Khan recorded live at the 2015 ASCO Annual Meeting.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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