Commentary on Abstracts #3118 and #2683
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.
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 (Ãsterborg 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.
