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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Radioimmunotherapy
Maximum Tolerated Dose
Non-Hodgkin's Lymphoma
Antibodies
Radiometry
Drug Therapy
Body Surface Area
Iodine
Hypotension
Histology
Therapeutics
Bone Marrow
Lymphocytes
Radiation

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., ... 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.

Maximum-tolerated dose, toxicity, and efficacy of 131I-Lym-1 antibody for fractionated radioimmunotherapy of non-Hodgkin's lymphoma. / Denardo, Gerald L; DeNardo, Sally J.; Goldstein, Desiree S.; Kroger, Linda A.; Lamborn, Kathleen R.; Levy, Norman B.; McGahan, John P; Salako, Qansy; Shen, Sui; Lewis, Jerry P.

In: Journal of Clinical Oncology, Vol. 16, No. 10, 10.1998, p. 3246-3256.

Research output: Contribution to journalArticle

Denardo, GL, DeNardo, SJ, Goldstein, DS, Kroger, LA, Lamborn, KR, Levy, NB, McGahan, JP, Salako, Q, Shen, S & Lewis, JP 1998, 'Maximum-tolerated dose, toxicity, and efficacy of 131I-Lym-1 antibody for fractionated radioimmunotherapy of non-Hodgkin's lymphoma', Journal of Clinical Oncology, vol. 16, no. 10, pp. 3246-3256.
Denardo, Gerald L ; DeNardo, Sally J. ; Goldstein, Desiree S. ; Kroger, Linda A. ; Lamborn, Kathleen R. ; Levy, Norman B. ; McGahan, John P ; Salako, Qansy ; Shen, Sui ; Lewis, Jerry P. / Maximum-tolerated dose, toxicity, and efficacy of 131I-Lym-1 antibody for fractionated radioimmunotherapy of non-Hodgkin's lymphoma. In: Journal of Clinical Oncology. 1998 ; Vol. 16, No. 10. pp. 3246-3256.
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title = "Maximum-tolerated dose, toxicity, and efficacy of 131I-Lym-1 antibody for fractionated radioimmunotherapy of non-Hodgkin's lymphoma",
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).",
author = "Denardo, {Gerald L} and DeNardo, {Sally J.} and Goldstein, {Desiree S.} and Kroger, {Linda A.} and Lamborn, {Kathleen R.} and Levy, {Norman B.} and McGahan, {John P} and Qansy Salako and Sui Shen and Lewis, {Jerry P.}",
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language = "English (US)",
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T1 - Maximum-tolerated dose, toxicity, and efficacy of 131I-Lym-1 antibody for fractionated radioimmunotherapy of non-Hodgkin's lymphoma

AU - Denardo, Gerald L

AU - DeNardo, Sally J.

AU - Goldstein, Desiree S.

AU - Kroger, Linda A.

AU - Lamborn, Kathleen R.

AU - Levy, Norman B.

AU - McGahan, John P

AU - Salako, Qansy

AU - Shen, Sui

AU - Lewis, Jerry P.

PY - 1998/10

Y1 - 1998/10

N2 - 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).

AB - 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).

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