Campath - 1H: Emerging Frontline Therapy in CLL

Campath - 1H: Emerging Frontline Therapy in Chronic Lymphocytic Leukemia
Edited by Kanti R. Rai and Janet Stephenson
Parthenon Publishing, New York, New York, 2001; 128 pages.

This book narrates the story of campath-1H from its inception to its commercialization. The authors describe the drug in detail as it relates to chronic lymphocytic leukemia (CLL), and briefly as it relates to T lymphocyte purging in bone marrow transplantation. The authors are well known experts in the area of CLL and each played pivotal roles in developing campath-1H. The authors review the clinical presentation and course of CLL in this easy-to-read 148-page book. They explore the recent genetic and chromosomal findings, the variable usefulness of different cytokines in evaluation of disease (i.e. ICAM-1 for measuring tumor motility; CD27 for measuring tumor mass, etc.). They then summarize the relevant information on single- and multi-agent chemotherapy trials for CLL and describe the development of the purine analogues pentostatin, fludarabine and cladribine.

Finally on page 51, they begin the story of monclonal antibodies in cancer and spend the rest of the book exploring campath-1H as it relates to CLL. The three pivotal studies (005,009,211) leading to FDA approval are described in detail. Combination of campath-1H with chemotherapy and with bone marrow transplantation is explored; although combinations with other monoclonal antiboides are not. Thus, the combination of rituximab with campath-1H, the former for purging lymphoid tissue and the latter for clearing blood and marrow, is left unexplored. The book concludes with a suggestion for earlier treatment of patients with CLL. The authors argue that early therapy with alkylators has not been a reasonable option because of mutagenic effects, susceptibility to drug resistance and lack of effect of alkylator drugs on tumor cells in G-0 cell cycle. Conversely however the authors argue that early treatment with campath-1H should be considered because it does not cause mutagenic effects, does not predispose to drug resistance, and does not have cell cycle specific benefits. The final pages of the book suggest that campath-1H should also be considered as compelementary pre-, or peri-, transplant therapy. Its special contributions to bone marrow transplantation benefits may be in lowering tumor burden, effectuating an in-vivo purge of tumor cells, an in vivo depletion of T lymphocytes to reduce graft versus host disease and also an in vivo depletion of B lymphocytes to prevent post-transplant EBV lymphoproliferative syndrome as commonly otherwise occurs after selective T-lymphocyte depletion.

Certain mysteries about campath-1H remain unexplored and even unquestioned in this book. For example, what does CD52 do and why is it necessary? Why does an antibody acting only on lymphocytes have myelousppressive effects? How does campath-induced lymphopenia resolve spontaneously even when patents remain on therapy? Is CD52 shed from tumor cells of patients with CLL? If so, does shedding lead to tumor resistance? And how does one integrate the disparate information of anti-CD52 as both an infertility drug (through inhibition of sperm motility) and as an anti-cancer drug? Is it possible that the two disparate findings could result from a similarity? Could CD52 after all be important in tumor cell biology, perhaps in allowing tumor cell motility analogous to ways in which it allows sperm cell motility? These and other questions could potentially lead to better understanding of the cancer process itself. If "therapy uncovers biology", as has been taught by our great mentors in hematology-oncology, then perhaps campath-1H treatment could truly impact on our understanding of cancer.

Reviewed for Bloodline by:
Dr. Paulette Mehta
Professor, Hematology-Oncology, University of Arkansas for Medical Sciences
The Myeloma Treatment and Research Center
the Central Arkansas Veterans Healthcare System
Little Rock, Arkansas.

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