FDA Approves Ibrutinib Plus Rituximab
Combo for CLL

Chemo-free Combination

Zosia Chustecka

April 22, 2020

Patients with newly diagnosed chronic lymphocytic leukemia or small lymphocytic leukemia have a new treatment option — a combination of the targeted agent ibrutinib (Imbruvica, Pharmacyclics/Janssen) with the immunologic agent rituximab (Rituxan, Roche/Genentech and generics).

The ibrutinib/rituximab combination has just received approval from the US Food and Drug Administration (FDA) for use in newly diagnosed CLL.  

Ibrutinib, a first-in-class Bruton's tyrosine kinase (BTK) inhibitor, was already approved for use as  monotherapy in CLL.

The new approval was based on data from the National Cancer Institute-sponsored E1912 study, which showed that the combination of ibrutinib with rituximab improved progression-free survival (PFS) when compared with the gold standard, chemoimmunotherapy of fludarabine, cyclophosphamide, and rituximab (FCR) in patients (age 70 and younger) with newly diagnosed CLL.

"The results from ECOG-ACRIN's E1912 clinical trial in previously untreated, younger adult patients and today's milestone [approval] represent a paradigm shift in how physicians can treat patients with CLL and may enable many to choose a nonchemotherapy treatment option," commented Brian Koffman, MD, CM (retired), cofounder and chief medical officer/executive vice-president of the CLL Society.

"In the 14 years since I was first diagnosed with CLL, the treatment landscape has advanced dramatically for the better, with ibrutinib continuing to play a pioneering role in defining what it means to live with this disease," he said in a statement.

These results were first presented at the American Society of Hematology annual meeting in 2018, and then published in 2019 in the New England Journal of Medicine, as previously reported  by Medscape Medical News.

At the ASH meeting, hematologic malignancy experts were enthusiastic about the E1912 results.

"These findings have immediate practice-changing implications and establish ibrutinib as the single most effective first-line therapy for patients with CLL," lead author Tait D. Shanafelt, MD, from Stanford University, California, told Medscape Medical News at the time.

The E1912 trial was one of three studies with ibrutinib in CLL reported in 2018, and also discussed at the meeting. Another large trial sponsored by the NCI, the ALLIANCE study, showed that ibrutinib alone was superior to the combination of bendamustine-rituximab in older patients (≥ 65 years of age) with CLL. Plus there was an industry-sponsored trial, the iLLUMINATE trial, which showed that the combination of ibrutinib and obinutuzumab (Gazyva, Roche/Genentech) improved PFS over that seen with chemotherapy with chlorambucil plus obinutuzumab.

"This is an embarrassment of riches," commented Aaron T. Gerds, MD, of the Cleveland Clinic Taussig Cancer Institute, Ohio. Ultimately, clinicians will have to weigh all the factors before deciding on the choices before them, he said.

As ibrutinib was already approved as a monotherapy for use in newly-diagnosed CLL, and a comparison between ibrutinib alone and ibrutinib plus rituximab is now unlikely to be carried out, there may never be solid data on which to base a choice of therapy between these two options.

"I think it is probably reasonable to choose either ibrutinib alone or in combination with rituximab in younger patients," Jennifer A. Woyach, MD, from Ohio State University Comprehensive Cancer, Columbus, told Medscape Medical News at the time. 

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