Lars Stenberg | PubMed Health

PubMed2005

Dose-fractionated radioimmunotherapy in non-Hodgkin's lymphoma using DOTA-conjugated, 90Y-radiolabeled, humanized anti-CD22 monoclonal antibody, epratuzumab.

PURPOSE: Fractionated radioimmunotherapy may improve therapeutic outcome by decreasing heterogeneity of the dose delivered to the tumor and by decreasing hematologic toxicity, thereby allowing an increased amount of radionuclide to be administered. Because humanized anti-CD22 epratuzumab can be given repeatedly, a single-center study was conducted to establish the feasibility, safety, optimal dosing, and preliminary efficacy of weekly administrations of 90Y-labeled 1,4,7,10-tetra-azacyclodecane-N,N',N'',N'''-tetraacetic acid-conjugated epratuzumab. EXPERIMENTAL DESIGN: Cohorts of three to six patients with B-cell lymphoma received 185 MBq/m2 [90Y]epratuzumab with unconjugated epratuzumab (total protein dose 1.5 mg/kg) once weekly for two to four infusions, with [(111)In]epratuzumab coadministered at first infusion for scintigraphic imaging and dosimetry. RESULTS: Sixteen patients received treatment without significant infusional reactions. The overall objective response rate was 62% (95% confidence interval, 39-86%) in both indolent (75%) and aggressive disease (50%). Complete responses (CR/CRu) occurred in 25% of patients and were durable (event-free survival, 14-41 months). Two patients receiving four infusions had hematologic dose-limiting toxicity. Serum epratuzumab levels increased with each weekly dose. Of 13 patients with tumor cell CD22 expression determined by flow cytometry, seven of eight with strongly positive results had objective responses, versus one of five with negative or weakly positive results (P = 0.032). CONCLUSIONS: Radioimmunotherapy with weekly 185 MBq/m2 [90Y]epratuzumab achieved a high objective response rate (62%) across lymphoma subtypes, including durable CRs. The findings that three weekly infusions (555 MBq/m2, total dose) can be administered safely with only minor toxicity, that antibody levels increased during treatment weeks, and that therapeutic response predominantly occurs in patients with unequivocal CD22 tumor expression provide guidance for future studies.

Adult↗

PubMed2003

Change in tumor-absorbed dose due to decrease in mass during fractionated radioimmunotherapy in lymphoma patients.

PURPOSE: In radionuclide therapy, cumulated activity and tumor volume/mass are the principal quantities necessary for the calculation of the absorbed dose to the tumor. When treating a fast-responding macroscopic tumor, there may be a decrease in its mass during therapy, and at any given uptake, this will result in an increase in the absorbed dose. The purpose of the present work is to demonstrate the limitations in current internal dosimetry protocols that assume a fixed tumor mass in lymphoma patients, using a fractionated radioimmunotherapy schedule and using a single infusion. EXPERIMENTAL DESIGN: Patients with B-cell lymphoma were treated with (90)Y-labeled epratuzumab (Immunomedics, Inc., Morris Plains, NJ) using a weekly dose-fractionation schedule for 2-4 weeks. They received either 185 MBq/m(2) (5 mCi/m(2)) in each infusion or, if they had a history of high-dose chemotherapy with stem cell rescue, 92.5 MBq/m(2) (2.5 mCi/m(2)) in each infusion. All patients received (111)In-labeled epratuzumab with the first infusion to verify tumor targeting and for dosimetry. The present report is based on three selected patients, in whom repeated assessments of tumor mass were possible. In two patients, (111)In-labeled epratuzumab was also coadministered with one of the subsequent treatments, i.e. during the second and third of two and three scheduled infusions. The tumor volume was determined from computer tomography images obtained before the first infusion and on different times after the infusion. An exponential equation was fitted to the decreasing mass of the tumor and implemented in the calculation of the absorbed dose. For comparison, the absorbed dose to the tumor was also calculated using the tumor volume determined from the baseline pretreatment computer tomography examination. RESULTS: The tumor volume for the patients changed rapidly. For one patient, the pretreatment volume was 19.5 ml, and for another patient, it was 840 ml. For these two patients, the ratio of tumor volume at the beginning of therapy compared with that after 8 days and 14 days of therapy was 0.7 and 0.8, respectively. This rapid decrease in volume and subsequent mass reduction result in an increase of mean absorbed dose to the tumor of as much as a factor of 1.75. CONCLUSIONS: At a given activity uptake, a decrease in tumor mass during therapy will significantly increase the calculated absorbed dose. Taking the change in tumor mass into account when calculating absorbed dose may improve the correlation between the mean absorbed dose to the tumor and the response to the therapy.

Antibodies, Monoclonal↗