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Prepublished online as a Blood First Edition Paper on June 7, 2002; DOI 10.1182/blood-2002-01-0159.
Submitted January 17, 2002
Accepted March 18, 2002
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 Bjorkholm, Per-Anders Broliden, Fredrik Celsing, Viktoria Hjalmar, Lars Mollgard, Peppy Rebello, Geoff Hale, Herman Waldmann, Hakan Mellstedt, and Anders Osterborg*
Departments of Hematology and Oncology, Karolinska Hospital, Stockholm, Sweden; Huddinge University Hospital, Stockholm, Sweden
Huddinge University Hospital, Stockholm, Sweden
Departments of Hematology and Oncology, Karolinska Hospital, Stockholm, Sweden
Department of Pathology, Therapeutic Antibody Center, Oxford, United Kingdom
* Corresponding author; email: gerd.stahlberg{at}ks.se.
This phase II study determined the efficacy and safety of alemtuzumab, a humanized anti-CD52 monoclonal antibody, delivered subcutaneously (s.c.) 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 s.c., three times per week (t.i.w.), from week 2-3 onwards. 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% 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+). 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% patients. Infections were rare, but 10% patients developed cytomegalovirus (CMV) re-activation. These patients rapidly responded to i.v. 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" flu-like symptoms and may reduce healthcare costs in comparison with the intravenous infusions.
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