Anti-CD22 90Y-epratuzumab tetraxetan combined with anti-CD20 veltuzumab: a phase I study in patients with relapsed/refractory, aggressive non-Hodgkin lymphoma - PubMed (original) (raw)
Clinical Trial
Anti-CD22 90Y-epratuzumab tetraxetan combined with anti-CD20 veltuzumab: a phase I study in patients with relapsed/refractory, aggressive non-Hodgkin lymphoma
Thomas E Witzig et al. Haematologica. 2014 Nov.
Abstract
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.
Copyright© Ferrata Storti Foundation.
Figures
Figure 1.
Imaging examples. (A) Anterior whole-body scintigraphic images in a patient with mantle cell lymphoma. Images acquired 30 minutes after intravenous infusion of 111In-epratuzumab tetraxetan (left) and then 1 week later (right) show antibody uptake over this period at sites of known tumor involvement in the mid-abdomen and bilateral iliofemoral lymph nodes. (B) Anterior whole-body scintigraphic images in a patient with diffuse large B-cell lymphoma. 111In image acquired 1 week after intravenous infusion of 111In-epratuzumab tetraxetan (left) compared to bremstrallung image acquired 1 week after first intravenous infusion of 90Y-epratuzumab tetraxetan (right). Arrows denote sites of known lymphomatous involvement. Although bremstrallung imaging has poorer spatial resolution, the pattern of uptake with 90Y-epratuzum-ab tetraxetan appears similar to that with 111In-epratuzumab tetraxetan. (C) 18F-FDG-PET images in a patient with diffuse large B-cell lymphoma who had a partial response to treatment as determined by CT and after retreatment achieved a complete response by CT. Of the intense uptake seen at sites of a known large left cervical mass and multiple liver metastases at baseline (left), uptake occurs only at the site of one liver metastasis following initial treatment (center), with no uptake seen following retreatment (right).
Figure 2.
Pharmacokinetics. (A) Mean serum levels of veltuzumab. All patients received 200 mg/m2 veltuzumab administered intravenously once a week for 4 consecutive weeks. Serum samples were obtained before and 30 minutes after each of the four infusions; 1, 2, 3 and 4 days after the last dose; and then 1, 2, 3, 4, 8, and 12 weeks later. Veltuzumab serum levels were determined by enzyme-linked immunosorbent assay with a minimum detectable level of 0.5 μg/mL. (B) Mean serum concentration of 111In-epratuzumab tetraxetan. All patients received a 5 mCi diagnostic dose of 111In-epratuzumab tetraxetan administered intravenously following the second weekly dose of veltuzumab. Serum samples were obtained 30 minutes, 1, 2 and 4 hours after infusion, and then 1, 2, 3, 4 or 5, and 6, 7 or 8 days later. At each time point, In disintegration counts per unit volume were measured in local nuclear medicine departments using a calibrated gamma well counter, corrected for 111In physical decay, and expressed as a percentage of the initial 30-minute value.
Figure 3.
B-cell blood levels. All patients received veltuzumab on days 1, 8, 15 and 22 with 90Y-epratuzumab administered on days 15 and 22. B-cell levels were obtained on treatment days and then 4 and 12 weeks later. Two patients had B-cell levels outside the display window on day 1 (544 and 1190 cells/mL).
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