Maximum-tolerated dose, toxicity, and efficacy of 131I-Lym-1 antibody for fractionated radioimmunotherapy of non-Hodgkin's lymphoma

Gerald L Denardo, Sally J. DeNardo, Desiree S. Goldstein, Linda A. Kroger, Kathleen R. Lamborn, Norman B. Levy, John P McGahan, Qansy Salako, Sui Shen, Jerry P. Lewis

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Abstract

Purpose: Lym-1, a monoclonal antibody that preferentially targets malignant lymphocytes, has induced remissions in patients with non-Hodgkin's lymphoma (NHL) when labeled with iodine 131 (131I). Based on the strategy of fractionating the total dose, this study was designed to define the maximum-tolerated dose (MTD) and efficacy of the first two, of a maximum of four, doses of 131I-Lym-1 given 4 weeks apart. Additionally, toxicity and radiation dosimetry were assessed. Materials and Methods: Twenty patients with advanced NHL entered the study a total of 21 times. Thirteen (62%) of the 21 entries had diffuse large-cell histologies. All patients had disease resistant to standard therapy and had received a mean of four chemotherapy regimens. 131I-Lym-1 was given after Lym-1 and 131I was escalated in cohorts of patients from 40 to 100 mCi (1.5 to 3.7 GBq)/m2 body surface area. Results: Mean radiation dose to the bone marrow from body and blood 131I was 0.34 (range, 0.16 to 0.63) rad/mCi (0.09 mGy/MBq; range, 0.04 to 0.17 mGy/MBq). Dose-limiting toxicity was grade 3 to 4 thrombocytopenia with an MTD of 100 mCi/m2 (3.7 GBq/m2) for each of the first two doses of 131I-Lym-1 given 4 weeks apart. Nonhematologic toxicities did not exceed grade 2 except for one instance of grade 3 hypotension. Ten (71%) of 14 entries who received at least two doses of 131I-Lym-1 therapy and 11 (52%) of 21 total entries responded. Seven of the responses were complete, with a mean duration of 14 months. All three entries in the 100 mCi/m2 (3.7 MBq/m2) cohort had complete remissions (CRs). All responders had at least a partial remission (PR) after the first therapy dose of 131I-Lym- 1. Conclusion: 131I-Lym-1 induced durable remissions in patients with NHL resistant to chemotherapy and was associated with acceptable toxicity. The nonmyeloablative MTD for each of the first two doses of 131I-Lym-1 was 100 mCi/m2 (total, 200 mCi/m2) (3.7 GBq/m2; total, 7.4 GBq/m2).

Original languageEnglish (US)
Pages (from-to)3246-3256
Number of pages11
JournalJournal of Clinical Oncology
Volume16
Issue number10
StatePublished - Oct 1998

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ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Denardo, G. L., DeNardo, S. J., Goldstein, D. S., Kroger, L. A., Lamborn, K. R., Levy, N. B., McGahan, J. P., Salako, Q., Shen, S., & Lewis, J. P. (1998). Maximum-tolerated dose, toxicity, and efficacy of 131I-Lym-1 antibody for fractionated radioimmunotherapy of non-Hodgkin's lymphoma. Journal of Clinical Oncology, 16(10), 3246-3256.