FDA Approves Imbruvica-Gazyva Combo for First-line Treatment of CLL/SLL

FDA Approves Imbruvica-Gazyva Combo for First-line Treatment of CLL/SLL

The U.S. Food and Drug Administration has approved a combination of Imbruvica (ibrutinib) and Gazyva (obinutuzumab) for the initial treatment of adults with chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL).

This is the first chemotherapy-free combination, containing a CD20 antibody, approved for first-line treatment of CLL/SLL.

“We are living in a time of significant advances in cancer treatment, particularly in blood cancers, and this latest Imbruvica FDA approval is an example. I am proud that we can now give physicians and patients a new option to treat CLL and SLL without the need for chemotherapy,” Danelle James, MD, head of clinical science at Pharmacyclics LLC, an AbbVie company, said in a press release.

Imbruvica is a potent inhibitor of Bruton’s tyrosine kinase (BTK) — a molecule needed for malignant B-cells to survive and proliferate — developed and commercialized by Janssen and Pharmacyclics.

The medicine is approved in the U.S. for six diseases, including CLL/SLL, both as a first treatment and for those who failed a prior treatment.

Gazyva (obinutuzumab) is a monoclonal antibody marketed by Genentech, a subsidiary of Roche. The drug binds to CD20, a protein expressed at the surface of B-cells, leading to the destruction of these cells, either directly or indirectly via immune system mediators.

A combination of Gazyva and the chemotherapy chlorambucil is approved in the U.S. for first-line treatment of CLL patients.

The recent approval was based on data from the Phase 3 iLLUMINATE trial (NCT02264574), where a combination of Gazyva and Imbruvica significantly delayed disease progression or death compared to Gazyva plus chlorambucil.

iLLUMINATE included 229 CLL/SLL patients from centers in Australia, Canada, Europe, Israel, New Zealand, Russia, Turkey, the United Kingdom, and the United States. Newly diagnosed patients who had never been treated were randomly assigned either Imbruvica or chlorambucil in combination with Gazyva.

Those assigned Imbruvica took three capsules per day (total of 420 milligrams daily) until their disease progressed or they no longer tolerated the medicine.

Gazyva was administered intravenously for six cycles of 28 days each. Chlorambucil was administered orally for six cycles of 28 days each.

Results showed that Imbruvica significantly extended the time patients lived without signs of disease worsening, compared with chemotherapy.

After 30 months of therapy, 79% of those receiving Imbruvica were alive and progression-free, compared to 31% in the control group — representing a 77% decrease in the risk of cancer progression or death.

Among patients with high-risk features, the benefits of Imbruvica were even more pronounced, with the treatment reducing the risk of disease progression or death by 85%.

Over a median follow-up of 31.3 months, only 4% of Imbruvica-treated patients required a second-line treatment, compared to 44% of those on chlorambucil.

The percentage of patients responding to the treatment was also higher with Imbruvica — 88% versus 73% — as was the proportion of patients experiencing total tumor clearance — 19% versus 8%.

Survival rates, however, were similar between both groups — 86% for Imbruvica and 85% for chlorambucil.

The data were recently published in The Lancet Oncology, in a study titled, “Ibrutinib plus obinutuzumab versus chlorambucil plus obinutuzumab in first-line treatment of chronic lymphocytic leukaemia (iLLUMINATE): a multicentre, randomised, open-label, phase 3 trial.”

“This latest Imbruvica FDA approval gives the healthcare community the first chemotherapy-free, anti-CD20 combination to treat CLL and SLL patients who have not yet started therapy. Also, and importantly, this new treatment combination helps reduce the need for chemotherapy,” said Carol Moreno, MD, PhD, iLLUMINATE’s lead investigator.

The FDA also agreed to update Imbruvica’s label with long-term data from the RESONATE (NCT01578707) and RESONATE-2 (NCT01722487) Phase 3 trials. These support the use of Imbruvica as a single agent for CLL/SLL patients who either are untreated or have failed prior treatments.

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