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 language | English (US) |
|---|---|
| Pages (from-to) | 3246-3256 |
| Number of pages | 11 |
| Journal | Journal of Clinical Oncology |
| Volume | 16 |
| Issue number | 10 |
| State | Published - Oct 1998 |
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ASJC Scopus subject areas
- Cancer Research
- Oncology
Cite this
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 journal › Article
}
TY - JOUR
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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UR - http://www.scopus.com/inward/citedby.url?scp=0031759837&partnerID=8YFLogxK
M3 - Article
C2 - 9779698
AN - SCOPUS:0031759837
VL - 16
SP - 3246
EP - 3256
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
SN - 0732-183X
IS - 10
ER -