FIRST NON-CHEMO REGIMEN FOR CLL

The US Food and Drug Administration (FDA) has approved ibrutinib (Imbruvica, Pharmacyclics and Janssen) in combination with obinutuzumab (Gazyva, Roche) for use in untreated patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL).

This is the first approval for a nonchemotherapy combination regimen for treatment-naive patients with CLL/SLL, according to a company statement.

Monotherapy with ibrutinib, which is a once-daily oral pill, was previously approved for frontline CLL/SLL use.

"In just a few years, ibrutinib has become an important treatment for chronic lymphocytic leukemia. Ibrutinib as a single agent — and now as a combination with obinutuzumab — provides patients with CLL with an alternative to frontline treatment with chemoimmunotherapy," Carol Moreno, MD, PhD, of the Autonomous University of Barcelona in Spain said in the statement.

Moreno was the lead investigator of the phase 3 iLLUMINATE trial, on which the new approval was based. Results from this trial were presented at the American Society of Hematology (ASH) 2018 Annual Meeting, as reported by Medscape Medical News.

With a median follow-up of 31 months, ibrutinib and obinutuzumab showed a significant improvement in progression-free survival compared with chlorambucilplus obinutuzumab (median not evaluable vs 19 months).

This translated into a 77% reduction in risk of progression or death with ibrutinib and obinutuzumab compared with chlorambucil and obinutuzumab (hazard ratio [HR], 0.23; 95% CI, 0.15 - 0.37; P < .0001).

Patients with high-risk disease (17p deletion/TP53 mutation, 11q deletion, or unmutated IGHV) treated with ibrutinib and obinutuzumab had even better results — an 85% reduction in risk of progression or death (HR, 0.15; 95% CI, 0.09 - 0.27). The overall response rate was 89% in the ibrutinib and obinutuzumab group versus 73% in the chlorambucil plus obinutuzumab group.

The most common adverse reactions (≥ 20%) of all grades in patients treated with ibrutinib and obinutuzumab in the study were neutropenia (48%), thrombocytopenia (36%), rash (36%), diarrhea (34%), musculoskeletal pain (33%), bruising (32%), cough (27%), infusion-related reaction (25%), hemorrhage (25%), and arthralgia (22%).

The label warnings and precautions include hemorrhage, infection, cytopenia, cardiac arrhythmia, hypertension, second primary malignancy, tumor lysis syndrome, and embryo-fetal toxicity.

The iLLUMINATE trial was sponsored by the ibrutinib manufacturers.

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