FDA News

FDA approves Imbruvica-Gazyva combination for treatment-naive chronic lymphocytic leukemia

The FDA approved ibrutinib for use in combination with obinutuzumab for treatment-naive patients with chronic lymphocytic leukemia or small lymphocytic lymphoma.

This is the first nonchemotherapy regimen indicated for this patient population.

Ibrutinib (Imbruvica; Pharmacyclics, Janssen), a Bruton tyrosine kinase inhibitor, already had been approved as monotherapy for CLL treatment. The agent also is approved for treatment of patients with small lymphocytic lymphoma and Waldenstrom macroglobulinemia, as well as patients with previously treated mantle cell lymphoma, marginal zone lymphoma and chronic graft-versus-host disease.

Obinutuzumab (Gazyva, Genentech) — an anti-CD20 monoclonal antibody — had been approved for use in combination with chlorambucil for patients with previously untreated CLL. It also is approved for treatment of certain patients with follicular lymphoma.

The FDA based the expanded approval on results of the phase 3 iLLUMINATE trial.

Researchers randomly assigned patients to 420 mg ibrutinib continuously in combination with 1,000 mg IV obinutuzumab over six cycles, or chlorambucil on days 1 and 15 of each cycle plus 1,000 mg IV obinutuzumab over six cycles.

Median follow-up was 31 months.

Results showed patients who received ibrutinib plus obinutuzumab achieved significantly longer median PFS as evaluated by an independent review committee (not evaluable vs. 19 months; HR = .023; 95% CI, 0.15-0.37).

The PFS benefit appeared even greater among patients with high-risk disease, such as those with 17p deletion, TP53 mutation, 11q deletion or unmutated immunoglobulin heavy chain gene (HR = 0.15; 95% CI, 0.09-0.27).

The independent review committee calculated overall response rates of 89% in the ibrutinib-obinutuzumab group and 73% in the chlorambucil-obinutuzumab group.

The most common all-grade adverse events reported among patients who received ibrutinib plus obinutuzumab 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%).

"In just a few years, Imbruvica has become an important treatment for chronic lymphocytic leukemia. Imbruvica 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, consultant hematologist at Hospital de la Santa Creu Sant Pau at Autonomous University of Barcelona and lead investigator of the iLLUMINATE study, said in a Janssen-issued press release.

The FDA previously granted priority review to the combination for this indication.

The FDA approved ibrutinib for use in combination with obinutuzumab for treatment-naive patients with chronic lymphocytic leukemia or small lymphocytic lymphoma.

This is the first nonchemotherapy regimen indicated for this patient population.

Ibrutinib (Imbruvica; Pharmacyclics, Janssen), a Bruton tyrosine kinase inhibitor, already had been approved as monotherapy for CLL treatment. The agent also is approved for treatment of patients with small lymphocytic lymphoma and Waldenstrom macroglobulinemia, as well as patients with previously treated mantle cell lymphoma, marginal zone lymphoma and chronic graft-versus-host disease.

Obinutuzumab (Gazyva, Genentech) — an anti-CD20 monoclonal antibody — had been approved for use in combination with chlorambucil for patients with previously untreated CLL. It also is approved for treatment of certain patients with follicular lymphoma.

The FDA based the expanded approval on results of the phase 3 iLLUMINATE trial.

Researchers randomly assigned patients to 420 mg ibrutinib continuously in combination with 1,000 mg IV obinutuzumab over six cycles, or chlorambucil on days 1 and 15 of each cycle plus 1,000 mg IV obinutuzumab over six cycles.

Median follow-up was 31 months.

Results showed patients who received ibrutinib plus obinutuzumab achieved significantly longer median PFS as evaluated by an independent review committee (not evaluable vs. 19 months; HR = .023; 95% CI, 0.15-0.37).

The PFS benefit appeared even greater among patients with high-risk disease, such as those with 17p deletion, TP53 mutation, 11q deletion or unmutated immunoglobulin heavy chain gene (HR = 0.15; 95% CI, 0.09-0.27).

The independent review committee calculated overall response rates of 89% in the ibrutinib-obinutuzumab group and 73% in the chlorambucil-obinutuzumab group.

The most common all-grade adverse events reported among patients who received ibrutinib plus obinutuzumab 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%).

"In just a few years, Imbruvica has become an important treatment for chronic lymphocytic leukemia. Imbruvica 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, consultant hematologist at Hospital de la Santa Creu Sant Pau at Autonomous University of Barcelona and lead investigator of the iLLUMINATE study, said in a Janssen-issued press release.

The FDA previously granted priority review to the combination for this indication.

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