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

Abstract

Background: Subcutaneous injections of anti-CD20 antibodies may offer benefits to both patients and the healthcare system for treatment of B-cell malignancies.

Design and methods: 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.

Results: 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.

Conclusions: 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).

Figures

Figure 1.

Mean serum levels of veltuzumab for each dose group. All patients received SC injections once every two weeks for a total of 4 administrations, with cohorts receiving veltuzumab at dose levels of 80 mg, 160 mg, or 320 mg. Serum samples were obtained at time of the 1st injection, 24, 48, 76, and 96 h later; at the 2nd, 3rd and 4th injections, 24, 48, 76 and 96 h after the 14th injection; and then 1, 2, 3, 4, 8, and 12 weeks later. Veltuzumab serum levels were determined by enzyme-linked immunosorbent assay. For plotting purposes, values too low to be measured were assigned the minimum detectable level of the assay (0.5 μg/mL).

Figure 2.

Circulating B-cell levels for patients having non-elevated levels at study entry. All patients received SC veltuzumab once every two weeks for a total of 4 administrations. Blood samples for B-cell levels were obtained at time of each injection and then 4, 8, 12, 24, 36, and 48 weeks after the 4th administration. Panels show results for cohorts receiving veltuzumab at 320 mg, 160 mg, or 80 mg (note change of scale for the 80 mg dose group).