Combined Anti-CD22 & Anti-CD20 MAbs Show Promise Against NHL (2002)

ORLANDO—The combined use of two very different monoclonal antibodies—epratuzumab (anti-CD22) and rituximab (anti-CD20) appear to be synergistically active against non-Hodgkin's lymphoma (NHL), with acceptable toxicity. That was the conclusion of preliminary Phase II data reported here at the ASCO Annual Meeting by a team led by John P. Leonard MD, Medical Director of Oncology Services and Assistant Professor of Medicine in the Division of Hematology and Medical Oncology at Weill Cornell Medical College in New York City. The trial, done in conjunction with researchers from the manufacturers, Amgen, Inc., and Immunomedics, suggest a beneficial anti-lymphoma effect without a change in the safety profile of rituximab, the only current antibody therapy for NHL The study involved 21 patients with relapsed and refractory NHL in whom the disease had progressed despite prior treatment with non-antibody agents. The two drugs were administered together, once a week for four weeks; the dosages were 360 mg/m2 intravenously for epratuzumab (also called E-mab) followed by rituximab at 375 mg/m2 IV. In Phase I studies, E-mab has shown brisk antitumor activity, Dr. Leonard explained in an interview. “Immunotherapy with epratuzumab directed at CD22 has shown clinical activity and acceptable toxicity in initial trials with relapsed and refractory NHL patients. Given the clinical benefits of CD20-directed therapy [i.e., with rituximab], we decided to explore the potential utility of targeting both antigens using the two antibodies in lymphoma. “We are hopeful when we see a consistent pattern of results as the number of treated patients increases and the duration of responses seen in follow-up grows,” he continued. “Complete response rates with the combination are higher than one would expect with rituximab alone. But side effects are comparable to what we see with rituximab alone. ” Shortened Infusion Time Another potential benefit may arise from the fact that the infusion time of E-mab is only about an hour compared with the usual four to six hours needed for rituximab. “That may one day represent important time- and- cost savings for both the physician and the patient,” he said. The men and women (median age of 63) in the trial had 16 indolent and five diffuse (aggressive) large cell NHL. In the indolent arm, 63 percent of patients (10 of 16) had an overall objective response. “This objective response rate is in the range of that observed with single-agent rituximab in other studies targeting similar patients,” Dr. Leonard emphasized. More noteworthy, however, he said, is that 90 percent of the responders (9 of 10) in the indolent NHL group achieved a complete response. Additionally, responses are still ongoing in all 10 of these objective responders as of 16 months of follow-up. This new combination treatment program resulted in a complete response rate of 56 percent, which is the highest yet reported in lymphoma with any form of antibody therapy, he said. As of now, no one has relapsed. Low-Grade Tumors Notoriously Difficult to Treat Asked to comment on the trial, lymphoma specialist David J. Straus, MD, an attending physician at Memorial Sloan-Kettering Cancer Center in New York City, noted that patients with low-grade lymphomas are very difficult to cure with systemic treatment. “A variety of therapies may be of benefit in some cases, “ Dr. Straus continued. “The disease seems to have an inexorable tendency to recur years later. What is most interesting in this study is the high complete response rate with the combination—much higher than with rituximab alone. But the study is very small and the follow-up very short. We need large trials extending as long as seven to eight years to know if the response is durable.” Patients with more aggressive NHL subtypes also responded to the two-pronged antibody treatment, although not as dramatically as did those with lower-grade disease. Dr. Leonard and his colleagues also stressed that no significant additional toxicity was observed in any of the patients—a striking difference from what typically occurs with other cancer treatments. In his poster presentation, Dr. Leonard gave the rationale for using the combination in NHL. First noting that rituximab is not a cure, he said: (1) About 50 percent of patients with indolent NHL studied do not respond to rituximab; (2) Only about 15 to 20 percent of patients have complete responses to rituximab; and (3) Responders eventually relapse, with a time to disease progression of 10.1 months. “Rituximab and epratuzumab pursue different targets, and have potentially different and non-overlapping mechanisms of action,” he said. One of his coauthors, Morton Coleman, MD, Director of Weill Cornell Center for Lymphoma and Myeloma, who was a discussant at the session at which the poster was discussed, summed up: “The promising initial results observed in this trial offer hope for a potential improvement in outcome for lymphoma patients while providing an alternative to chemotherapy. It is also the first clinical trial combining separate antibodies with distinct targets in NHL therapy.”