Campath-1H is an unconjugated, humanized monoclonal antibody directed against the CD52 antigen present on B cells, as well as T cells and other mononuclear cells. In phase II trials, this antibody has shown impressive activity in chronic lymphocytic leukemia (CLL) and T-cell prolymphocytic leukemia (T-PLL) but limited activity in NHL (Österborg et al: J Clin Oncol 15:1567-1574, 1997; Pawson et al: J Clin Oncol 15:2667-2672, 1997; Lundin et al: J Clin Oncol 16:3257-3263, 1998). In CLL, responses to Campath-1H have been reported in 30% to 70% of patients who had not responded to prior treatment, including fludarabine (Fludara), with complete response (CR) rates ranging from 4% to 50%. More than two-thirds of T-PLL patients have achieved CRs, but these do not seem to be durable. Only 14% of patients with low-grade NHL achieved partial responses (PRs), although responses were noted in about half of a small number of patients with mycosis fungoides.
The promising preliminary results of Campath-1H in CLL led to a multicenter phase II trial that will be used as the licensing study for this agent (Keating et al, abstract #3118). The trial included 92 heavily pretreated patients; to be eligible, patients had to have been unresponsive to fludarabine as one of their prior therapies. The overall response rate was 33%, including 2% CRs. The median time to progression was 9 months. More than half of these patients developed infections, one-third of which were serious, life-threatening, or fatal.
In another trial including 29 patients with CLL (Kennedy et al, abstract #2683), response to Campath-1H was assessed by looking for minimal residual disease (MRD) in complete responders. Of the 10 patients who achieved a CR, 5 had no detectable MRD. The event-free and overall survival rates were better in this subset of patients. In both of these studies, bulky adenopathy predicted for a poor response.
Campath-1H will likely be an effective addition to the therapeutic options for patients with CLL. However, strategies to reduce the frequency of infections associated with this agent need to be identified.
Bruce D. Cheson, MD