Campath-1H is an anti-CD52 monoclonal antibody that has demonstrated impressive activity in patients with relapsed chronic lymphocytic leukemia (CLL) and in those with T-cell prolymphocytic leukemia (T-PLL). Initial clinical trials with this agent were terminated early because of excessive toxicity, ie, myelosuppression and infections. Nevertheless, the investigators were impressed by the activity of the antibody in patients with advanced CLL.
A less intensive schedule was developed and has now been used in a series of protocols. Österborg et al (J Clin Oncol 15:1567-1574, 1997) first described 29 patients with refractory or relapsed CLL with a response rate of 42%, including a 4% rate of complete remissions. Pawson et al (J Clin Oncol 15:2667-2672, 1997) reported on 15 patients with T-PLL, many of whom had already not responded to a purine analog. These patients had a 60% complete remission rate, with an overall response rate of 73%.
Österborg et al (abstract #1718) now report their results with 50 patients with advanced low-grade NHL treated with Campath-1H. The response rate was surprisingly low at 20%, including two (4%) complete remissions. Although lymphoma cells were rapidly cleared from the blood in 94% of patients, a complete response in the bone marrow was induced in only 32%, and lymph nodes returned to normal size in only 5%.
The failure to resolve lymphadenopathy is similar to what has been observed with rituximab(Drug information on rituximab). The explanation for this finding is unknown and may reflect an inability of the antibody to penetrate into the node. Lymphopenia was pronounced in the study of Österborg et al, with seven patients experiencing an opportunistic infection, and nine cases of septicemia. Future studies should evaluate the use of prophylactic antimicrobial agents to reduce the morbidity associated with Campath-1H , and alternate schedules of administration should be explored to minimize toxicity while maintaining efficacy.
- Bruce D. Cheson, MD