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Combination therapy effective for diffuse large B-cell lymphoma
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ATLANTA — Lenalidomide and obinutuzumab with CHOP chemotherapy induced an overall response rate of 98% among patients with newly diagnosed diffuse large B-cell lymphoma, according to results of a phase 1/phase 2 study presented at the ASH Annual Meeting and Exposition.
Ninety percent of patients experienced a complete response, according to the report.
“The combination was well tolerated with similar toxicities to R-CHOP and nothing jumping out as a significantly different toxicity for this combination,” Jason R. Westin, MD, assistant professor of lymphoma and myeloma at The University of Texas MD Anderson Cancer Center, said during his presentation. “We saw high overall and complete response rates, and excellent PFS and OS. We met our primary endpoint with [greater than 75% response rates].”
With 30,000 diagnoses a year, DLBCL is the most common lymphoid cancer in the United States. Standard therapy of rituximab (Rituxan; Genentech, Biogen) and CHOP chemotherapy results in a cure rate of about 60%.
Lenalidomide (Revlimid, Celgene), a potent immunomodulatory agent, and obinutuzumab (Gazyva, Genentech), a humanized CD20 monoclonal antibody, have shown promising efficacy and acceptable toxicity among patients with DLBCL. As single agents, they have induced response rates ranging from 28% to 32%.
However, obinutuzumab may have increased antibody dependent cell-mediated cytotoxicity, and lenalidomide is toxic to DLBCL via interferon signaling stimulation.
Researchers examined if the combination of obinutuzumab, lenalidomide and CHOP would result in a complete response rate greater than the 57% rate reported for obinutuzumab and CHOP in the GOYA trial at the 2016 ASH Annual Meeting and Exposition.
Fifty-one patients aged 18 years or older with newly diagnosed, CD20-positive DLBCL and adequate organ function received 1,000 mg IV obinutuzumab (days 1, 8 and 15 during cycle 1, and day 1 on cycles 2 through 6) and 15 mg lenalidomide (days 1 through 14 in cycles 1 through 6, with lower doses if toxicities occurred). Once researchers identified the maximum-tolerated dose, they initiated the phase 2 trial with a planned total of at least 50 evaluable patients.
Determining maximum-tolerated dose and evaluating the efficacy of lenalidomide and obinutuzumab with CHOP served as the primary outcome measures.
Among the 51 patients in the cohort, the median age was 62 years (range, 26-83), 58% were women, the median International Prognostic Index was 2.
Researchers identified no dose-limiting toxicities in phase 1b trial. Toxicities encountered included neutropenia (grade 3, 50%; grade 4, 33%), thrombocytopenia (grade 3, 17%) and rash (grade 2, 17%).
Among 50 patients in the phase 2 cohort, 45 had a complete response, four had partial response and one experienced progression.
“We had a relatively high percentage of dizziness (55% any grade), which is not something I have not encountered too much with R-CHOP or lenalidomide,” Westin said. “We also had a high incidence of fatigue (98%), but it was very mild and nobody had to come off [therapy] because of fatigue.”
In the combined evaluable patients, the overall response rate was 98%, which included a 90% complete response rate. Researchers reported complete response rates of 90% in nongerminal center subtype and 92% in germinal center.
Median follow-up was 11 months; median PFS and OS had not been not reached. No deaths occurred.
Limitations of the study included the fact it was a single-arm, single-center study, researchers noted.
“Next year, we could potentially present the combination of rituximab, lenalidomide and ibrutinib as a lead-in for newly diagnosed, nongerminal center large cell lymphoma with some very impressive results so far,” Westin said. – by Chuck Gormley
Reference:
Westin JR, et al. Abstract 189. Presented at: ASH Annual Meeting and Exposition; Dec. 9-12, 2017; Atlanta.
Disclosures: Westin reports advisory roles with Apotex, Celgene, Kite Pharma and Novartis. Please see the abstract for all other authors’ relevant financial disclosures.