A lingering criticism of
radioimmunotherapy in
non-Hodgkin lymphoma is the use of cold anti-CD20 antibody along with the radiolabeled anti-CD20 antibody. We instead combined
radioimmunotherapy with
immunotherapy targeting different B-cell
antigens. We evaluated the anti-CD22 (90)Y-epratuzumab
tetraxetan with the anti-CD20
veltuzumab in patients with aggressive
lymphoma in whom at least one prior standard treatment had failed, but who had not undergone
stem cell transplantation. Eighteen patients (median age 73 years, median of 3 prior treatments) received 200 mg/m(2)
veltuzumab once-weekly for 4 weeks, with (90)Y-epratuzumab
tetraxetan at planned doses in weeks 3 and 4, and (111)In-epratuzumab
tetraxetan in week 2 for imaging and dosimetry.
Veltuzumab effectively lowered levels of B cells in the blood prior to the
radioimmunotherapy doses. No significant immunogenicity or change in pharmacokinetics of either agent occurred in combination. (111)In imaging showed
tumor targeting with acceptable radiation dosimetry to normal organs. For (90)Y-epratuzumab
tetraxetan, transient myelosuppression was dose-limiting with 6 mCi/m(2) (222 MBq/m(2)) × 2 being the maximal tolerated dose. Of 17 assessable patients, nine (53%) had objective responses according to the 2007 revised treatment response criteria, including three (18%) complete responses (2 relapsing after 11 and 13 months, 1 continuing to be clinically disease-free at 19 months), and six (35%) partial responses (1 relapsing after 14 months, 5 at 3 - 7 months). Responses occurred in patients with different
lymphoma histologies, treated at different (90)Y dose levels, and with a predicted risk of poor outcome, most importantly including five of the six patients treated with the maximal tolerated dose (2 of whom achieved durable complete responses). In conclusion, the combination of (90)Y-epratuzumab
tetraxetan and
veltuzumab was well-tolerated with encouraging therapeutic activity in this difficult-to-treat population.