A phase 2 trial of extended induction epratuzumab and rituximab for previously untreated follicular lymphoma: CALGB 50701

Abstract

Rituximab combined with chemotherapy has improved the survival of previously untreated patients with follicular lymphoma (FL). Nevertheless, many patients neither want nor can tolerate chemotherapy, leading to interest in biological approaches. Epratuzumab is a humanized anti-CD22 monoclonal antibody with efficacy in relapsed FL. Since both rituximab and epratuzumab have single agent activity in FL, we evaluated the antibody combination as initial treatment of patients with FL. Patients and Methods Fifty-nine untreated patients with FL received epratuzumab 360 mg/m2 with rituximab 375 mg/m2 weekly for four induction doses. This combination was continued as extended induction in weeks 12, 20, 28, and 36. Response assessed by CT was correlated with clinical risk factors, FDG-PET findings at week 3, Fcg polymorphisms, immunohistochemical markers, and statin use. Results Therapy was well-tolerated with toxicities similar to expected with rituximab monotherapy. Fifty-two (88.2%) evaluable patients responded, including 25 complete responses (CR)(42.4%), and 27 partial responses (45.8%). At 3 years follow-up, 60% of patients remain in remission. Follicular Lymphoma International Prognostic Index (FLIPI) risk strongly predicted progression-free survival (p=0.022). Conclusions The high response rate and prolonged time to progression observed with this antibody combination are comparable to those observed after standard chemo-immunotherapies and further support the development of biologic, non-chemotherapeutic approaches for these patients.

CALGB 150905 (Alliance): Rituximab Broadens the Antilymphoma Response by Activating Unlicensed NK Cells

“…To test whether the ability of rituximab to activate unlicensed NK cells (without cytokines, transplantation, or chemotherapy) is clinically significant, we genotyped one hundred and one FL patients treated with mAb alone [CALGB protocols 50402 (rituximab with galiximab) and 50701 (rituximab with epratuzumab)] (23, 24) and compared PFS between patients with and without a “missing KIR ligand” genotype (Table 2, Supplemental Figure 6). The median PFS estimate for all patients was 3.74 years.…”

“…Patients were treated with a non-cytotoxic strategy of rituximab-containing antibody combinations on CALGB protocols 50402 (rituximab with galiximab) and 50701(rituximab with epratuzumab) from 2005 through 2009. (23, 24) Forty-six of 62 patients (74%) from CALGB 50402 consented and had samples available, although one patient never began treatment and was excluded from the analysis. Fifty-six of 60 patients (93%) from CALGB 50701 consented and had samples available.…”

“…We further tested the clinical significance of our in vitro findings in a cohort of follicular lymphoma patients treated with rituximab-containing antibody combinations (23, 24). …”

Frontline strategy for follicular lymphoma: are we ready to abandon chemotherapy?

“…32 Grant and colleagues reported an ORR of 88%, with 60% of patients remaining in remission at 3 years with the anti-CD22 antibody epratuzumab combined with rituximab. 33 The immunomodulatory drug lenalidomide has both direct antineoplastic activity and affects the tumor microenvironment through mediation of B, T, natural killer (NK), and dendritic cells. In experimental B-cell models, lenalidomide appears synergistic with multiple agents, including rituximab, dexamethasone, and BCR pathway inhibitors.…”

Are We Nearing an Era of Chemotherapy-Free Management of Indolent Lymphoma?

“…Concurrent administration of rituximab and epratuzumab, used first line for patients with follicular lymphoma, produced an ORR of 88% and CR of 42% as well as a prolonged response duration (60% of patients still in remission after 3 years; ref. 36).…”