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Prepublished online as a Blood First Edition Paper on June 7, 2002; DOI 10.1182/blood-2002-01-0159.
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Blood, 1 August 2002, Vol. 100, No. 3, pp. 768-773
CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS
Phase II trial of subcutaneous anti-CD52 monoclonal antibody
alemtuzumab (Campath-1H) as first-line treatment for patients with
B-cell chronic lymphocytic leukemia (B-CLL)
Jeanette Lundin,
Eva Kimby,
Magnus Björkholm,
Per-Anders Broliden,
Fredrik Celsing,
Viktoria Hjalmar,
Lars Möllgård,
Peppy Rebello,
Geoff Hale,
Herman Waldmann,
Håkan Mellstedt, and
Anders Österborg
From the Departments of Hematology and Oncology,
Karolinska Hospital, and Huddinge University Hospital, Stockholm,
Sweden; and Therapeutic Antibody Center, Oxford, United Kingdom.
This phase II study determined the efficacy and safety of
alemtuzumab, a humanized anti-CD52 monoclonal antibody, delivered subcutaneously as first-line therapy, over a prolonged treatment period
of 18 weeks in 41 patients with symptomatic B-cell chronic lymphocytic
leukemia (B-CLL). Injections were administered subcutaneously 3 times
per week, from week 2 to 3 onward. An overall response rate (OR) of
87% (95% CI, 76%-98%; complete remission [CR], 19%; partial
remission [PR], 68%) was achieved in 38 evaluable patients (81% of
intent-to-treat population). CLL cells were cleared from blood in 95%
patients in a median time of 21 days. CR or nodular PR in the bone
marrow was achieved in 66% of the patients and most patients achieved
this after 18 weeks of treatment. An 87% OR (29% CR) was achieved in
the lymph nodes. The median time to treatment failure has not yet been
reached (18+ months; range, 8-44+ months). Transient injection site
skin reactions were seen in 90% of patients. Rigor, rash, nausea,
dyspnea, and hypotension were rare or absent. Transient grade IV
neutropenia developed in 21% of the patients. Infections were rare,
but 10% patients developed cytomegalovirus (CMV) reactivation. These
patients rapidly responded to intravenous ganciclovir. One patient,
allergic to cotrimoxazole prophylaxis, developed
Pneumocystis carinii pneumonia. Alemtuzumab is
highly effective as first-line treatment in patients with B-CLL.
Prolonged treatment is important for maximal bone marrow response.
Subcutaneous administration induced very few "first-dose" flulike
symptoms and may reduce health care costs in comparison with the
intravenous infusions.
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