Epratuzumab, a New Anti-CD22, Humanized, Monoclonal Antibody for the Therapy of Non-Hodgkin’s Lymphoma: Phase I/II Trial Results

OncologyONCOLOGY Vol 14 No 3
Volume 14
Issue 3

Epratuzumab is a humanized anti-CD22 monoclonal antibody immunoglobulin G1 (hLL2 [LymphoCide]) that has been studied in radiolabeled forms (iodine-131[131I] and yttrium-90 [90Y]) in the treatment of chemotherapy-refractory

Epratuzumab is a humanized anti-CD22 monoclonal antibody immunoglobulin G1 (hLL2 [LymphoCide]) that has been studied in radiolabeled forms (iodine-131[131I] and yttrium-90 [90Y]) in the treatment of chemotherapy-refractory non-Hodgkin’s lymphoma (NHL). The aim of this trial is to assess the safety and efficacy of escalating doses of the naked (unlabeled) form of epratuzumab in patients with NHL who relapsed after chemotherapy.

At least six patients (three with indolent and three with aggressive lymphomas) were treated with four weekly infusions of epratuzumab at each of five dose levels, ranging from 120 to 600 mg/m² per injection. To date, 30 patients have been enrolled, with 25 currently assessable for toxicity and response.

Dose-limiting toxicity has not been observed, and the 1-hour infusions have been tolerated well at all dose levels. No drug-related grade 3 or 4 toxicity has been observed; only grade 2 hypotension (N = 2) and grade 1 rigors and fatigue (N = 3 each) were noted, primarily during the initial infusion. All other drug-related events were only grade 1, including blood count or chemistry changes.

Serum immunoglobulin levels have not been affected, nor has there been evidence of pharmacokinetic changes following repeated injections. There is no evidence of a significant antihuman antibody response.

Reduction in circulating CD22-positive cells has been observed in several patients. No responses were seen at dose level 1 (120 mg/m²/wk). One diffuse large cell lymphoma patient treated at dose level 2 (240 mg/m²/wk), who previously relapsed after chemotherapy and autologous stem-cell transplantation and who was also unresponsive to rituximab (Rituxan) therapy, has achieved an ongoing complete remission (CR) for over 1 year. Two of three indolent NHL patients treated at dose level 3 (360 mg/m²/wk) responded (1 CR, 1 partial response [PR]), as well as two of three indolent NHL patients treated at dose level 4 (480 mg/m²/wk; 1 CR, 1 PR). Four of these five responses are ongoing.

Epratuzumab levels were detectable in the serum for up to 3 months after treatment, and patients with objective responses had higher circulating levels.

CONCLUSION: Epratuzumab is well tolerated across a wide range of protein doses given as a 1-hour infusion, and can result in objective tumor responses. These results suggest that the antibody is a potential new therapy for NHL that may be effective in cases of rituximab failure. Further dose escalation in larger numbers of patients is ongoing to determine the optimal dose and response rate.

Click here for Dr. Bruce Cheson’s commentary on this abstract.

Articles in this issue

Comparative Economic Analysis of the Treatment of Relapsed Low-Grade B-Cell Non-Hodgkin’s Lymphoma (NHL) in France Using CHOP, Fludarabine, or Rituximab
FHIT Gene, Smoking, and Cervical Cancer
Final Report on the Safety and Efficacy of Retreatment With Rituximab for Patients With Non-Hodgkins Lymphoma
Prospective, Randomized, Controlled Study of Zevalin Radioimmunotherapy Compared to Rituximab Immunotherapy for B-Cell, Non-Hodgkins Lymphoma: Interim Results
IOM Medical Error Estimates Questioned, But Legislation Considered
Less Toxic Therapies for Hodgkin’s Disease May Reduce Secondary Cancers
Preserving Fertility in Young Women With Ovarian Cancer Does Not Decrease Survival
Iodine-131 Tositumomab for Patients With Transformed, Low-Grade Non-Hodgkin’s Lymphoma: Overall Clinical Trial Experience
Survival Rates Significantly Worse For African-Americans With Endometrial Cancer
Rituximab Has Significant Activity in Patients With Chronic Lymphocytic Leukemia
Responders to Rituximab Show Continued Tumor Regression Over Time and a Progression-Free Survival That Correlates With Response Classification
PhRMA Criticizes FDA’s Proposed Rule on Antibiotic Approvals
Phase II Study of Rituximab in Combination With CHOP in Patients With Previously Untreated Intermediate- or High-Grade Non-Hodgkin’s Lymphoma
New Antibiotic Effective in Treating Gram-Positive Bacteremia
Reduced-Dose Zevalin Radioimmunotherapy for Relapsed or Refractory B-Cell Non-Hodgkin’s Lymphoma Patients With Preexisting Thrombocytopenia: Report of Interim Results of a Phase II Trial
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