SwitzerlandCombination monoclonal antibody treatment of lymphoid
malignancies may be as safe as single-antibody therapy, and produces a better overall response rate, new data suggest. The data come from a
recent study of 48 heavily pretreated, poor-prognosis patients treated with the
combination of alemtuzumab (Campath-1H) and rituximab (Rituxan), presented at
the 8th International Conference on Malignant Lymphoma (ICML).
Responses were seen "in all anatomic compartments,
indicating activity of this combination," said Stefan Faderl, MD,
assistant professor, Department of Leukemia, University of Texas M.D. Anderson
Single-agent monoclonal antibody therapy can achieve high
response rates in patients with chronic lymphocytic leukemia (CLL) and various
histologies of non-Hodgkin’s lymphoma. However, these agents are not curative
by themselves. The rationale for combining alemtuzumab and rituximab, both of
which have proven single-agent activity in these disorders, is that the two
together may achieve a synergistic treatment effect, Dr. Faderl explained.
Rituximab targets the CD20 antigen, ubiquitously expressed
in B-cell lympho-proliferative disorders, while alemtuzu-mab targets CD52,
which is the most abundantly expressed glycoprotein on CLL cells, he said.
Synergism may come from the suboptimal activity of either monoclonal antibody
in a specific disease site (ie, bone marrow) or from complementary modes of
To test the combination, Dr. Faderl and his colleagues
enrolled CD20- and CD52-positive patients with relapsed or refractory lymphoid
malignancies. Previous exposure to either antibody was allowed.
Median patient age was 61 years, and 77% were Rai stage 3 or
greater. About half were refractory to fludarabine (Fludara). Most (33 of 48)
patients had CLL, while 8 had CLL/PLL (prolympho-cytic leukemia). The rest had
PLL (1), mantle cell lymphoma (4), and Richter’s transformation of CLL (2).
The 4-week treatment included rituxi-mab 375 mg/m²
once weekly plus alem-tuzumab on an escalating dose schedule (3, 10, and 30 mg
during week 1, and 30 mg on days 3 and 5 for the next 3 weeks).