Subcutaneous injections of low-dose veltuzumab (humanized anti-CD20 antibody) are safe and active in patients with indolent non-Hodgkin’s lymphoma

• Published in: Haematologica (Roma) Vol. 96; no. 4; pp. 567 - 573
• Main Authors: NEGREA, George O, ELSTROM, Rebecca, ALLEN, Steven L, RAI, Kanti R, ABBASI, Rashid M, FARBER, Charles M, TEOH, Nick, HORNE, Heather, WEGENER, William A, GOLDENBERG, David M
• Format: Journal Article
• Language: English
• Published: Pavia Ferrata Storti Foundation 01-04-2011
• Subjects: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal - adverse effects; Antibodies, Monoclonal - pharmacokinetics; Antibodies, Monoclonal, Humanized; Antigens, CD20 - metabolism; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - adverse effects; Antineoplastic Agents - pharmacokinetics; Biological and medical sciences; Female; Hematologic and hematopoietic diseases; Hematologic Tests; Humans; Injections, Subcutaneous; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Lymphoma, Non-Hodgkin - drug therapy; Lymphoma, Non-Hodgkin - pathology; Male; Medical sciences; Middle Aged; Neoplasm Staging; Original; Treatment Outcome; Human; CD20; antibody; Hematology; Subcutaneous; Low dose; hA20; Malignant hemopathy; subcutaneous therapy; Non Hodgkin lymphoma; Anti-CD20; Treatment; non-Hodgkin's lymphoma; Lymphoproliferative syndrome; Humanized antibody; Indolent lymphoma; Cancer
• ISSN: 0390-6078; 1592-8721
• DOI: 10.3324/haematol.2010.037390

Subcutaneous injections of anti-CD20 antibodies may offer benefits to both patients and the healthcare system for treatment of B-cell malignancies.
A pilot study was undertaken to evaluate the potential for subcutaneous dosing with 2(nd) generation anti-CD20 antibody veltuzumab in patients with CD20(+) indolent non-Hodgkin's lymphoma. Patients with previously untreated or relapsed disease received 4 doses of 80, 160, or 320 mg veltuzumab injected subcutaneously every two weeks. Responses were assessed by computed tomography scans, with other evaluations including adverse events, safety laboratories, B-cell blood levels, serum veltuzumab levels, and human anti-veltuzumab antibody (HAHA) titers.
Seventeen patients (14 follicular lymphoma; 13 stage III or IV disease; 5 treatment-naive) completed treatment with only occasional, mild-moderate, transient injection reactions and no other safety issues. Subcutaneous veltuzumab demonstrated a slow release pattern over several days, achieving a mean Cmax of 19, 25 and 63 μg/mL at 80, 160, and 320 mg doses for a total of 4 administrations, respectively. Depletion of circulating B cells occurred after the first injection. The objective response rate (partial responses plus complete responses plus complete responses unconfirmed) was 47% (8/17) with a complete response/complete response unconfirmed rate of 24% (4/17); 4 of 8 objective responses continued for 60 weeks or more. All serum samples evaluated for human anti-veltuzumab antibody were negative.
Subcutaneous injections of low-dose veltuzumab are convenient, well tolerated, and capable of achieving sustained serum levels, B-cell depletion, and durable objective responses in indolent non-Hodgkin's lymphoma. (Clinicaltrials.gov identifier: NCT00546793).