Study coauthor Jacqueline Claudia Barrientos, MD, associate professor at the Feinstein Institutes for Medical Research in New York, emphasized that the study does not provide any evidence that the addition of rituximab improved outcomes or remission duration beyond what is achieved by ibrutinib alone. Because the study didn’t include an ibrutinib-monotherapy arm, there’s no way to know. “I don’t believe that we should move to using combination ibrutinib plus rituximab for frontline except in specific cases, such as uncontrolled autoimmune complications or in a patient with a very aggressive disease that requires combined therapy because monotherapy is taking too long to work,” Dr Barrientos said.

She also pointed out that widespread use of ibrutinib as a frontline treatment would raise several issues. Although ibrutinib appears to cause less myelosuppression than FCR, she said, “there are still other issues that can affect quality of life.” These include bleeding, joint pain, diarrhea, cardiac arrhythmias, and other side effects. Dr Barrientos noted that because ibrutinib needs to be taken indefinitely, sorting out these complications is vital. 

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Cost is another concern. Again, the long-term nature of ibrutinib therapy is the issue: the drug may be too expensive to sustain treatment. In a 2015 paper in the Journal of Oncology Practice, Dr Shanafelt discussed the potential financial burden that would confront the movement toward novel targeted agents, such as ibrutinib, for frontline treatment of CLL.3 This shift, Dr Shanafelt wrote, “will dramatically increase individual out-of-pocket and societal costs of caring for patients with CLL. These cost considerations may undermine the potential promise of these agents by limiting access and reducing adherence.” 

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Nitin Jain, MD, associate professor of medicine at MD Anderson Cancer Center, Houston, Texas, who was not involved with the study, was optimistic about the findings. The results, he said, were not just statistically significant but also clinically significant.  “This study establishes a new treatment paradigm for younger patients with CLL,” he says. However, he emphasized that this benefit is restricted to patients with IGVH-unmutated disease, per the study findings.

As Dr Jain sees it, the study is just one more piece of the puzzle showing how ibrutinib and new drugs may best benefit patients with CLL. “Several ongoing randomized studies are evaluating combinations of targeted therapies with chemoimmunotherapy,” Dr Jain noted. “The results of these studies will further help define the optimal frontline approach for patients with CLL.”

Disclosure: The study was supported by the National Cancer Institute and Pharmacyclics. Some of the authors of the study reported receiving payments from the pharmaceutical industry. For a full list of disclosures, please refer to the original study.


  1. Burger JA, Tedeschi A, Barr PM, et al. Ibrutinib as initial therapy for patients with chronic lymphocytic leukemia. N Engl J Med. 2015;373(25):2425-2437.
  2. Shanafelt TD, Wang XV, Kay NE, et al. Ibrutinib–Rituximab or chemoimmunotherapy for chronic lymphocytic leukemia. N Engl J Med. 2019;381(5):432-443.
  3. Shanafelt TD, Borah BJ, Finnes HD, et al. Impact of ibrutinib and idelalisib on the pharmaceutical cost of treating chronic lymphocytic leukemia at the individual and societal levels. J Oncol Pract. 2015;11(3):252-258.