Imbruvica Regimen Improves Survival Outcomes in Younger Patients with CLL

The combination use of Imbruvica (ibrutinib) with Rituxan (rituximab) significantly improved survival outcomes compared with standard of care in younger patients with chronic lymphocytic leukemia (CLL), according to phase 3 study results presented at the 2018 American Society of Hematology (ASH) Annual Meeting.

Chronic lymphocytic leukemia is one of the most common lymphoid malignancies, accounting for 11 percent of lymphoid neoplasms,” lead investigator Tait D. Shanafelt, M.D., from Stanford University, said during his presentation at the meeting, held Dec. 1 through 4, in San Diego.

"(Fludarabine, cyclophosphamide and Rituxan [FCR]) is a (regimen) with high side effects and cannot be tolerated by all CLL patients, and it primarily is given to those age 70 or younger," he added. "This new regimen is well-tolerated and had fewer side effects than our previous standard therapy."

FCR is a six-month course of chemotherapy-based treatment that has demonstrated significant efficacy among patients with CLL, especially in those aged 70 and younger. However, results from a head-to-head phase 3 trial showed that patients who were treated with Imbruvica plus Rituxan had a two-thirds reduction in the risk of disease progression with a significant improvement in overall survival compared with those treated with standard of care.

This is due, in part, because Imbruvica interrupts or targets a specific enzyme, Bruton’s tyrosine kinase, that is known to help CLL cells survive. “(Imbruvica) targets the Achilles’ heel of CLL cells, whereas previous chemotherapy was much less targeted,” Shanafelt explained in a press release.

Therefore, the researchers conducted the phase 3 ECOG-ACRIN Cancer Research Group (E1912) study — designed to evaluate the efficacy and safety of Imbruvica plus Rituxan (354 patients) compared with FCR (175 patients) in those with previously untreated, symptomatic CLL.

After a median follow-up of 33.4 months, patients treated with Imbruvica/Rituxan experienced a 65 percent reduction in the risk for disease progression or death, also known as progression-free survival, compared with FCR. In addition, the combination reduced the risk for death, also known as overall survival, by 83 percent.

In subgroup analyses for progression-free survival, Imbruvica was superior to FCR independent of age, sex, daily living abilities and disease stage.

Treatment-related grade 3/4 side effects were significantly lower with Imbruvica/Rituxan compared with FCR (58.5 percent vs 72.1 percent), including neutropenia (22.7 percent vs. 43.7 percent, respectively), anemia (2.6 percent vs. 12 percent), thrombocytopenia (2.9 percent vs. 13.9 percent), and neutropenic fever (2.3 percent vs. 15.8 percent). Other side effects included infection (5.4 percent vs. 8.2 percent), diarrhea (2.6 percent vs. 0.6 percent), hypertension (7.4 percent vs. 1.9 percent), bleeding (1.1 percent vs. 0 percent) and atrial fibrillation (2.9 percent vs. 0 percent).

The researchers noted that they will continue to monitor patients to determine the durability of these results and how they evolve over time.

“We know FCR does some collateral damage to the immune system that can be long-lasting and leave patients vulnerable to infections, whereas ibrutinib can enhance immune function,” Shanafelt said. “Understanding the long-term effects of these two therapies on the immune system and the risk of infection will be very informative.”