Ibrutinib Combo in Chronic Lymphocytic Leukemia is Superior, but Costly


While ibrutinib plus rituximab may improve progression-free survival in chronic lymphocytic leukemia, it is a costly option for some patients.

In the first-line setting, ibrutinib plus rituximab had a superior survival benefit to standard chemoimmunotherapy for patients with chronic lymphocytic leukemia (CLL), according to an interim analysis of a phase III randomized clinical trial published in the New England Journal of Medicine.

Study researchers also noted that “indefinite” use of ibrutinib therapy has been associated with “substantial expense.” According to the IBM Micromedex, the estimated average wholesale price per month for ibrutinib alone is more than $13,324. A 2018 study found that at current prices, ibrutinib was not cost-effective as first-line treatment for CLL patients older than 65 years of age with a 17p deletion.

The trial enrolled 529 patients between March 2014 and June 2016 who were 70 years of age or younger with treatment-naïve CLL. Patients were randomly assigned in a 2:1 ratio to receive either 6 cycles of ibrutinib plus rituximab followed by continuous administration ibrutinib until disease progression (n=354) or 6 cycles of standard chemoimmunotherapy (n=175), which consisted of fludarabine, cyclophosphamide, and rituximab. Follow-up was a median of 33.6 months.

At 3 years, patients who received ibrutinib plus rituximab had a statistically higher progression-free survival (PFS) rate and 65% lower risk of disease progression or death compared with patients who received standard chemoimmunotherapy (89.4% vs 72.9%; HR=0.35; 95% CI, 0.22–0.56; P<0.001). Patients who received ibrutinib plus rituximab also had a significantly higher overall survival (OS) rate and an 83% lower risk of death compared with patients who received standard chemoimmunotherapy (98.8% vs 91.5%; HR=0.17; 95% CI, 0.05–0.54; P<0.001).

Overall, both the ibrutinib plus rituximab and chemoimmunotherapy groups had approximately an 80% incidence of adverse events of grade 3 or higher. There was, however, a difference in infection complications of grade 3 or higher, with the ibrutinib plus rituximab group having a lower incidence compared with the chemoimmunotherapy group (10.5% vs 20.3%; P<0.001).

The incidence of adverse events of grade 3 or higher (regardless of attribution) was similar in the two groups (in 282 of 352 patients [80.1%] who received ibrutinib–rituximab and in 126 of 158 [79.7%] who received chemoimmunotherapy), whereas infectious complications of grade 3 or higher were less common with ibrutinib–rituximab than with chemoimmunotherapy (in 37 patients [10.5%] vs. 32 [20.3%], P<0.001).

“I don’t think one hundred percent of people should be getting ibrutinib as frontline therapy,” Joshua Brody, MD, director of the Lymphoma Immunotherapy Program at the Icahn School of Medicine at Mount Sinai Hess Center for Science and Medicine in New York, told Cancer Network.

On the basis of the study results, he explained the ibrutinib combination is “definitely” a “reasonable” option and “better” than fludarabine, cyclophosphamide, and rituximab, but it’s not “definitely” better than rituximab plus bendamustine, which is the other chemoimmunotherapy regimen commonly used in this patient population. 

A previously published trial in treatment-naive CLL patients found a PFS benefit among those who received ibrutinib monotherapy or ibrutinib plus rituximab when compared with rituximab plus bendamustine. However, no OS benefit was seen for the ibrutinib-containing regimens. 

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