¹³¹I-Anti CD20 Radioimmunotherapy of Relapsed or Refractory Non-Hodgkins Lymphoma: A Phase II Clinical Trial of a Nonmyeloablative Dose Regimen of Chimeric Rituximab Radiolabeled in a Hospital

Abstract

In order to increase the availability and affordability of radioimmunotherapy of refractory or relapsed non-Hodgkins lymphoma, we developed and evaluated radioiodinated rituximab in an ongoing physician-sponsored Phase II Clinical Trial. The chimeric 1gG(1) anti CD 20 monoclonal antibody rituximab was radiolabeled with iodine-131 using a modified Chloramine T method with high radiochemical purity (98% +/- 0.82) and preservation of immunoreactivity. All patients received therapeutic loading doses of unlabeled rituximab (375 mg/m(2)) immediately prior to administration of tracer (200 MBq (131)I) or therapy (1.7-4.3 GBq (131)I) activities of (131)I-rituximab to provide additive immunotherapy and enhance tumor uptake of the radiolabeled antibody. Objective response rate (ORR) was 71% in 35 patients with a median follow-up of 14 months (range 4-28 months). Complete remission (CR) was achieved in 54% of patients, with median duration 20 months. Toxicity evaluation included an additional 7 patients followed for at least 3 months. Tracer dosimetry studies were performed in each patient and the whole body radiation absorbed dose was limited to a mean prescribed dose (MPD) of 0.75 Gy. Myelosuppression was reversible and in only 2 of 42 patients was grade IV hematological toxicity observed. No hemopoietic support was required in any patient. There was no instance of hemorrhage or infection in this group of patients in each of whom individual prospective dosimetry was performed prior to (131)I rituximab radioimmunotherapy for relapsed or refractory non-Hodgkins lymphoma.

Radioimmunotherapy of relapsed indolent non-Hodgkin lymphoma with 131I-rituximab in routine clinical practice: 10-year single-institution experience of 142 consecutive patients

“…This large patient variation emphasizes the need for personalized individual dosimetry, in the absence of which patients may be significantly under-or overdosed by up to 20%-30%. 20 The reported myelotoxicity of 131 I-tositumomab is similar to our experience of 131 I-rituximab, in which self-limited grade 4 neutropenia occurred in 16% and grade 4 thrombocytopenia in 4% of patients undergoing RIT. There is little evidence to suggest significant long-term toxicities attributable to RIT.…”

“…Our pharmacokinetic studies of tracer activities of 131 I-rituximab in patients with NHL confirm that, while the circulation time (mean, 86 hours) is longer than that of 131 I-tositumomab (mean, 56 hours), the absorbed radiation dose is comparable. 20 In particular, direct measurement of red marrow dose in a cohort of our patients demonstrated that a whole-body radiation-absorbed dose of 0.75 Gy correlated with a radiation-absorbed dose to hemopoietic marrow, which did not exceed the toxicity threshold of 2 Gy. 21 Furthermore, the bone marrow clearance of 131 I-rituximab appeared to be the same as the whole-body clearance and is likely to reflect that of 131 Itositumomab.…”

“…20 Radiolabeling yield was more than 98%, and the immunoreactive fraction of 131 I-labeled anti-CD20 antibody was more than 80%. 20 A tracer activity of 200MBq 131 I-rituximab was given intravenously after administration of a standard dose of 375 mg/m 2 rituximab unlabeled antibody. Within 1 hour, whole-body gamma imaging and background scans were performed and were repeated at 4 and 7 days under the same quantitative imaging conditions.…”

“…The residence time of 131 I-rituximab was calculated from whole-body gamma-camera counts at these time points. 20 The radioimmunotherapeutic activity was administered 7 days later after a prior 375 mg/m 2 loading dose of unlabeled rituximab. The administered activity was calculated to deliver a whole-body radiation-absorbed dose of 0.75 Gy.…”

“…19 We evaluated our 10-year, single-center clinical experience with 131 I-rituximab for the therapy of relapsed or refractory indolent, mainly follicular NHL, in 142 patients treated on a compassionate patient-usage protocol, including 66 patients reported in a multicenter phase 2 clinical study. 7 The prescribed radionuclide therapy activity was based upon prospective individualized dosimetry to the whole body as a surrogate for red marrow, 20 which allowed a nonmyeloablative effective treatment without causing significant myelosuppression or other toxicity.…”