Monoclonal antibody therapy with CAMPATH-1H in patients with relapsed high- and low-grade non-Hodgkin's lymphomas: a multicenter phase I/II study

Abstract

CAMPATH-1H (CP-1H) is a humanized monoclonal antibody directed against the CD52 antigen with promising therapeutic effects in patients with small cell lymphocytic non-Hodgkin's lymphomas (NHL) of B- and T-cell type. We report about the response and toxicity of CP-1H in 18 patients with B-cell NHL who were treated in four clinical centers in Germany. Sixteen patients suffered from a low-grade and two from a high-grade NHL. All patients had received chemotherapy before and had either relapsed or were refractory to conventional therapy. Two patients received CP-1H in a dose-range finding trial once weekly and 16 patients as a fixed dose of 30 mg three times weekly. Of 18 patients, 8 (44%) achieved a clinical response, 2 (11%) had stable disease, and 5 (28%) had progressive disease. Four patients could not be evaluated for response because of death (two patients) and serious adverse events (two patients). All patients with response to CP-1H had a low-grade NHL. Nonhematological toxicity was severe in two patients who suffered from WHO grade III/IV bronchospasm. Common acute adverse events (WHO grade I-III) included fever, chills, rigor, urticaria, nausea, and vomiting. Eleven patients suffered from bacterial or viral infections; some had recurrent infections. A total of 12 different infections were reported. The most frequent infections were caused by herpesvirus (seven patients). Hematological toxicity included thrombocytopenia in four and lymphocytopenia in seven patients. Although the antibody is humanized, the nonhematological toxicity was substantial and probably due to a cytokine release syndrome. Prophylactic treatment of the side effects is strongly recommended for patients treated either with CP-1H alone or in combination with chemotherapy.

The use of monoclonal antibodies for the treatment of epithelial ovarian cancer (review)

“…In recent clinical studies in non-Hodgkin lymphoma patients, antibody-based therapy has shown remarkable response rates and, for this reason became a standard element in the treatment of these malignancies (5,6). Similar results were obtained with antibody-based therapies in several solid malignancies (7)(8)(9).…”

Homing and mobilization of hematopoietic stem cells and hematopoietic cancer cells are mirror image processes, utilizing similar signaling pathways and occurring concurrently: circulating cancer cells constitute an ideal target for concurrent treatment with chemotherapy and antilineage-specific antibodies

“…167,168 However, in the high doses currently used, Campath-1H is toxic as single agent or in combination with chemotherapy in CLL patients and particularly in NHL patients. [169][170][171] It is important to stress that in the proposed model of concurrent chemotherapy and antibody therapy, relatively low doses of chemotherapy are sufficient to mobilize tumor cells to the peripheral blood, much lower than the currently used doses for concurrent chemotherapy and antilineage-specific antibody. Therefore, it is anticipated that the observed immunosuppression and hematological toxicities will be markedly reduced with an increase in the therapeutic index.…”

Cardiac toxicity of alemtuzumab in patients with mycosis fungoides/Sézary syndrome

“…Sixty-five percent of patients who receive alemtuzumab therapy experience lymphopenia and opportunistic infections, especially reactivation of cytomegalovirus and herpes viruses. 1,2,[7][8][9] Although less frequent, pulmonary and cardiac events also may occur in patients treated with alemtuzumab 2,3,7-9 and may necessitate discontinuation of the therapy. In our experience with alemtuzumab, particularly those with mycosis fungoides (MF) or Sézary syndrome (MF/SS), there appeared to be a higher than acceptable risk of cardiac complications.…”