Imbruvica Yields Favorable Safety Outcomes in Two Types of Lymphomas

Imbruvica (ibrutinib) is a safe treatment for patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and mantle cell lymphoma (MCL), according to a pooled analysis of four clinical trials.

Researchers from the United States and seven other countries (United Kingdom, Canada, Italy, France, Germany, Spain and The Netherlands) examined the findings of the following phase 3 studies: RESONATE, RESONATE-2, HELIOS and RAY. All the trials compared oral Imbruvica, a type of kinase inhibitor that works by blocking the B-cell protein Bruton’s tyrosine kinase, with another type of cancer medication.

The RESONATE trial randomly assigned patients with CLL/SLL to receive either Imbruvica or Arzerra (ofatumumab) given intravenously (IV). RESONATE-2 compared the treatment of Imbruvica versus the oral chemotherapy medication chlorambucil in patients with CLL/SLL. In HELIOS, all patients with CLL/SLL received IV Treanda (bendamustine) plus Rituxan (rituximab) and were randomly assigned to Imbruvica or placebo. And in the RAY trial, patients with MCL either received Imbruvica or the chemotherapy drug temsirolimus, which was given through IV.

Across all trials, 756 patients were treated with Imbruvica for a median of 13.3 months and 749 patients were treated with the other cancer medications for a median of 5.8 months. The median age of patients was 67 years, most were white and had two previous lines of therapy.

Discontinuation of treatment was higher among patients who did not receive Imbruvica compared with those who did, 85 percent versus 27 percent, respectively. And many patients discontinued treatment because of progressive disease.

Patients in both groups experienced side effects including infections, gastrointestinal disorders, diarrhea, muscle spasms and joint pain. Neutropenia (low white blood cell count), thrombocytopenia (low blood platelet count) and pneumonia were the three most common grade 3 or 4 side effects. The grade 3 or 4 rates of diarrhea (3 percent), atrial fibrillation (6 percent) and hypertension (4 percent) were higher with Imbruvica than with the comparators.

“There were no surprises that came out of a very large patient analysis,” Susan O’Brien, M.D., University of California, Irvine, said in an interview with CURE. “In most cases, these toxicities are grade 1 to grade 2, and they tend to occur early. The only one that can go up over time is hypertension and that is easy to monitor when patients come into clinic and have vital signs done.”

O’Brien, who serves as associate director for clinical sciences at the Chao Family Comprehensive Cancer Center and medical director of the Sue and Ralph Stern Center for Cancer Clinical Trials & Research, noted that this analysis is very reassuring for researchers and patients.

“Ibrutinib is an extremely effective drug,” she said. “Patients generally tolerate the drug quite well and they can stay on it for extended periods of time and have very good results.”

Deaths because of side effects occurred at similar rates: 6 percent in the Imbruvica groups versus 7 percent in the control groups.

Imbruvica is approved by the Food and Drug Administration (FDA) to treat patients with CLL/SLL; CLL/SLL with 17p deletion; Waldenström's macroglobulinemia; adult patients with MCL who have received at least one prior treatment; patients with marginal zone lymphoma who require a medicine by mouth or injection and have received a certain type of prior treatment; and chronic graft versus host disease after failure of one or more lines of systemic therapy.