NEW YORK (FRONTLINE MEDICAL NEWS) – Obinutuzumab monotherapy was effective for the first-line treatment of chronic lymphocytic leukemia in a small study of patients with a high rate of unmutated immunoglobulin heavy-chain variable region (IGHV) genes.

The overall response rate to obinutuzumab, a type 2 anti-CD20 humanized monoclonal antibody, was 100% in 20 previously untreated patients. Median progression-free survival was 30 months, and no deaths occurred at a median of 23 months follow-up, Nathan D. Gay, MD, reported in a poster at the annual meeting of the International Workshop on Chronic Lymphocytic Leukemia (iwCLL).

The good results imply that initial monotherapy may be an alternative approach that limits the toxicity associated with the recommended combination of chlorambucil and obinutuzumab.

At the time of analysis, 3 of the 20 patients (15%) had relapsed, and the mean time to next line therapy was 29 months,” Dr. Gay of Oregon Health & Science University, Portland and his colleagues wrote. Minimal residual disease (MRD) analysis completed in 16 patients showed that 5 (31%) were MRD-negative 6 months after the completion of therapy.

Study participants were adults with a median age of 62.5 years and a median cumulative illness rating scale score of 6.5 on the 0-56 scale. Most (80%) had unmutated IGHV and none harbored 17p deletion. All met iwCLL diagnostic criteria for CLL based on peripheral blood counts and flow cytometry,

All but one patient received 6 cycles of intravenous obinutuzumab given at 100 mg on day 1, 900 mg on day 2, 1000 mg on days 8 and 15 of the first cycle, and 1000 mg on day 1 for cycles 2-6.

The remaining patient discontinued treatment after two cycles because of grade 4 neutropenia.

Obinutuzumab is approved for use in combination with oral chlorambucil in patients with previously untreated CLL. The approval was based on the CLL11 study, which demonstrated improved overall response, complete response rate, and peripheral blood MRD negativity rates with obinutuzumab plus chlorambucil, vs. rituximab plus chlorambucil, the authors said. Based on those findings, obinutuzumab plus chlorambucil is considered a standard of care option in treatment-naive CLL lacking del(17p)/TP53 mutation in patients who are not candidates for first-line therapy with fludarabine, cyclophosphamide, and rituximab (FCR).

However, while chlorambucil is generally well tolerated, it has limited efficacy and is associated with overall grade 3-4 toxicity of about 44%. Obinutuzumab has significant single-agent activity in previously untreated CLL and was shown in a recent phase 2 dose-response study to be associated with an overall response rate of 49%-67% and complete response rates of 5%-20%, but data on the efficacy of first line obinutuzumab monotherapy using standard dosing outside of a clinical trial are lacking, they said.

The current study represents an analysis of all patients treated with first line obinutuzumab monotherapy at Oregon Health & Science University.

In the current study, the most common side effects were infusion reactions and cytopenias. Grade 3 or higher neutropenia, anemia, and thrombocytopenia occurred in 32%, 11%, and 32% of patients, respectively, and one patient developed a grade 3 infection.

“In our cohort of patients with untreated CLL, we found first line obinutuzumab monotherapy to be very effective and well tolerated,” they wrote, noting that this was true despite a high rate of unmutated IGHV. “These data, using first-line obinutuzumab monotherapy, compare favorably with combination therapy with chlorambucil.

“Omitting chlorambucil from this combination in favor of initial obinutuzumab monotherapy may eliminate the short- and long-term toxicity associated with the use of chemotherapy,” they concluded.

The authors reported having no disclosures.


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