Safety and efficacy of subcutaneous Campath-1H for treating residual disease in patients with chronic lymphocytic leukemia responding to fludarabine

• Published in: Haematologica (Roma) 2002-07, Vol.87 (7), p.695-700
• Main Authors: Montillo, M, Cafro, AM, Tedeschi, A, Brando, B, Oreste, P, Veronese, S, Rossi, V, Cairoli, R, Pungolino, E, Morra, E
• Format: Article
• Language: English
• Subjects: Adult; Alemtuzumab; Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal - toxicity; Antibodies, Monoclonal, Humanized; Antibodies, Neoplasm - administration & dosage; Antibodies, Neoplasm - toxicity; Antineoplastic agents; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - toxicity; Biological and medical sciences; Chemotherapy; Female; Humans; Injections, Subcutaneous; Leukemia, Lymphocytic, Chronic, B-Cell - complications; Leukemia, Lymphocytic, Chronic, B-Cell - drug therapy; Leukemia, Lymphocytic, Chronic, B-Cell - therapy; Male; Medical sciences; Middle Aged; Neoplasm, Residual - drug therapy; Pharmacology. Drug treatments; Therapeutic Equivalency; Treatment Outcome; Vidarabine - administration & dosage; Vidarabine - analogs & derivatives
• ISSN: 0390-6078; 1592-8721

Divisione di Ematologia, Dipartmento di Ematologia, Ospedale Niguarda Ca' Granda, piazza Ospedale Maggiore 3, 20162 Milan, Italy. [e-mail] BACKGROUND AND OBJECTIVES: Recent observations suggested that targeted monoclonal antibodies might be best employed in lymphoid malignancies under conditions of minimal residual disease. This prompted us to investigate the role of Campath-1H as treatment for patients with chronic lymphocytic leukemia (CLL) in whom fludarabine (FAMP) had produced a marked disease debulking with persistence of bone marrow (BM) infiltration or a complete remission (CR) without the disappearance of the molecular aberration (IgH monoclonal expression). As intravenous Campath-1H is almost invariably associated with reactions, sometimes of WHO grade 3-4, we adopted the subcutaneous route of administration, which proved to induce rare and mild adverse reactions but had comparable efficacy. DESIGN AND METHODS. Nine patients (7 males, 2 females) with a median age of 55 years (range 41-61) who responded to FAMP (1 had a CR, 5 a nodular partial remission [PRN], and 3 a partial remission [PR]), according to NCI Working Group Criteria, received subcutaneous Campath-1H, three times a week for 6 weeks in escalating doses up to 10 mg. Monoclonal rearrangement of IgH was present in all patients before immunotherapy. Patients received acyclovir and cotrimoxazole as infection prophylaxis. Granulocyte colony-stimulating factor (G-CSF), at the dosage of 5-10 microg/kg/die, or intermediate-dose Ara-C (800 mg/m(2)/q 12h x 6 doses), was administered to obtain peripheral blood stem cell (PBSC) mobilization. RESULTS: All patients were evaluable for response. Five patients, 2 in PR and 3 in PRN after FAMP treatment, reached a CR. Three patients, one in PR, one in PRN and one in CR, converted to a molecular remission. In four out of seven patients PBSC harvesting was successful; more than 2.5 x 10(6) cells/kg were collected from all these patients. Collection was polyclonal for IgH gene rearrangement in three cases. One patient has been transplanted after cyclophosphamide and total body irradiation as conditioning regimen, without complications and with rapid hemopoietic engraftment. All patients were evaluable for toxicity. A WHO grade 1-2 skin reaction was observed in 5 patients at the site of injection. No infectious episodes were recorded. Two out of three patients presenting cytomegalovirus reactivation, without pneumonia, were successfu