Ofatumumab combined with CHOP in previously untreated patients with follicular lymphoma (FL).

Abstract

8042^ Background: Ofatumumab (OFA) is a human antibody that targets a membrane-proximal epitope encompassing the small- and large-loop on CD20. Single-agent OFA has demonstrated clinical activity in relapsed/refractory FL at doses up to 1,000 mg. We report results from a phase II trial of OFA with CHOP (O-CHOP) in patients (pts) with FL. Methods: The planned sample size was N=56; 59 pts with previously untreated CD20+ FL (Grade 1–3, stage III–IV or bulky stage II) were randomized to OFA Day 1,500 mg (Group A) or 1,000 mg (Group B); cyclophosphamide Day 3, 750 mg/m2; doxorubicin Day 3, 50 mg/m2; vincristine Day 3, 1.4 mg/m2; and prednisolone Days 3–7, 100 mg every 3 weeks for 6 cycles. First OFA dose was 300 mg for both groups. One pt withdrew before treatment and was excluded from analysis. Primary endpoint was overall response rate (ORR; 1999 International Working Group criteria) assessed by an Independent Endpoint Review Committee. Results: 29 pts were enrolled into each group; 93 and 100% of pts in Groups A and B, respectively, received all 6 cycles of therapy. Baseline characteristics for Group A / Group B were: median age, 55 / 54 years; FLIPI score 3–5, 34% / 38% of pts. ORR (95% CI) was 90% (73, 98%) in Group A and 100% (88, 100%) in Group B. Complete response (CR) + unconfirmed CR (CRu) was 69% in Group A and 55% in Group B. Overall, 16 of 21 pts (76%) with FLIPI score 3–5 attained CR/CRu. Median follow-up was 9.7 months. OFA infusion-related reactions were primarily grade 1–2 and decreased in incidence with continued therapy; 2 pts (Group B) had grade 3 reactions during first dose, but were able to receive subsequent doses. The most common investigator-reported grade 3–4 adverse events were leukopenia and neutropenia (31 and 28%, Group A; 28 and 17%, Group B). Incidences of grade 3–4 leukopenia and neutropenia by laboratory assessments were 83 and 90% in Group A and 72 and 90% in Group B, respectively. Grade 3–4 infections occurred in 10% of pts in Group A and 3% in Group B, with febrile neutropenia in 7 and 3% of pts, respectively. No deaths have been reported. Additional data will be presented. Conclusions: O-CHOP achieved high response rates, was effective across all FLIPI risk groups and was well tolerated with no unexpected toxicities in previously untreated FL. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genmab, GlaxoSmithKline, Matrix-Bio Genmab, GlaxoSmithKline Genmab, GlaxoSmithKline Genmab, GlaxoSmithKline Genmab, GlaxoSmithKline In compliance with the guidelines established by the ASCO Conflict of Interest Policy (J Clin Oncol. 2006 Jan 20;24[3]:519-521) and the Accreditation Council for Continuing Medical Education (ACCME), ASCO strives to promote balance, independence, objectivity, and scientific rigor through disclosure of financial and other interests, and identification and management of potential conflicts. According to the ASCO Conflict of Interest Policy, the following financial and other relationships must be disclosed: employment or leadership position, consultant or advisory role, stock ownership, honoraria, research funding, expert testimony, and other remuneration (J Clin Oncol. 2006 Jan 20;24[3]:520). The ASCO Conflict of Interest Policy disclosure requirements apply to all authors who submit abstracts to the Annual Meeting. For clinical trials that began accrual on or after April 29, 2004, ASCO's Policy places some restrictions on the financial relationships of principal investigators (J Clin Oncol. 2006 Jan 20;24[3]:521). If a principal investigator holds any restricted relationships, his or her abstract will be ineligible for placement in the 2010 Annual Meeting unless the ASCO Ethics Committee grants an exception. Among the circumstances that might justify an exception are that the principal investigator (1) is a widely acknowledged expert in a particular therapeutic area; (2) is the inventor of a unique technology or treatment being evaluated in the clinical trial; or (3) is involved in international clinical oncology research and has acted consistently with recognized international standards of ethics in the conduct of clinical research. NIH-sponsored trials are exempt from the Policy restrictions. Abstracts for which authors requested and have been granted an exception in accordance with ASCO's Policy are designated with a caret symbol (^) in the Annual Meeting Proceedings. For more information about the ASCO Conflict of Interest Policy and the exceptions process, please visit www.asco.org/conflictofinterest.