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)
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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, developedPneumocystis 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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Acute subcutaneous infusion-related reactions such as rigor, rash or urticaria, nausea, hypotension, or bronchospasm were rare or absent in contrast to previous intravenous infusions.
“Furthermore, acute subcutaneous IRRs, such as rigor, rash or urticaria, nausea, hypotension, or bronchospasm, were rare or absent in contrast to the observations previously made for intravenous infusions [81].”
From Subcutaneous Administration of Biotherapeutics: An Overview of Current Challenges and Opportunities (2018) · cites this paper as [81]
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- Authors
- Lundin, J., Kimby, E., Björkholm, M., Broliden, P.-A., Celsing, F., Hjalmar, V., Möllgård, L., Rebello, P., Hale, G., Waldmann, H., Mellstedt, H., & Österborg, A.
- Affiliations
- Karolinska University Hospital (SE)
- From the Departments of Hematology and Oncology, Karolinska Hospital, and Huddinge University Hospital, Stockholm, Sweden; and Therapeutic Antibody Center, Oxford, United Kingdom.
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2002-08-01
- Volume
- 100
- Issue
- 3
- Pages
- 768-773
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W2169167811
- Cited by
- 497
- References
- 24
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 3 · 2023: 2 · 2022: 6 · 2021: 4 · 2020: 7 · 2019: 7 · 2018: 9 · 2017: 9 · 2016: 17 · 2015: 15 · 2014: 16 · 2013: 21 · 2012: 18
- FWCI
- 20.74
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Blood (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Insamlingsstiftelsen Cancer- och Allergifonden
- Cancerfonden
- Gunnar Nilssons Cancerstiftelse
- Cancerföreningen i Stockholm
- Takeda Oncology
- Medical Research Council
- Topics
- Health Sciences › Medicine › Genetics › Chronic Lymphocytic Leukemia Research
- Health Sciences › Medicine › Pathology and Forensic Medicine › Lymphoma Diagnosis and Treatment
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Acute Lymphoblastic Leukemia research
- Keywords
- alemtuzumab, chronic lymphocytic leukemia, anti-CD52 monoclonal antibody, subcutaneous administration, first-line therapy, complete remission, bone marrow response, cytomegalovirus reactivation, ganciclovir, Pneumocystis carinii pneumonia, neutropenia, injection site reactions, treatment safety
- MeSH terms
- CD52 Antigen, Alemtuzumab, Adult, Aged, Antibodies, Monoclonal, Antibodies, Neoplasm, Antigens, Neoplasm, Antineoplastic Agents, Follow-Up Studies, Glycoproteins, Humans, Injections, Subcutaneous, Middle Aged, Remission Induction, Leukemia, Lymphocytic, Chronic, B-Cell, Antigens, CD, Treatment Outcome, Antibodies, Monoclonal, Humanized
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