用于非霍奇金淋巴瘤分次放射免疫治疗的（131）I-Lym-1抗体的最大耐受剂量、毒性及疗效

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

作者信息

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

机构信息

Department of Internal Medicine, University of California Davis Medical Center, Sacramento, USA.

出版信息

J Clin Oncol. 1998 Oct;16(10):3246-56. doi: 10.1200/JCO.1998.16.10.3246.

DOI:10.1200/JCO.1998.16.10.3246

PMID:9779698

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 ((131)I). 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 (131)I-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. (131)I-Lym-1 was given after Lym-1 and (131)I 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 (131)I was 0.34 (range, 0. 1 6 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 (131)I-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 (131)I-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 (131)I-Lym-1.

CONCLUSION

(131)I-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 (131)I-Lym-1 was 100 mCi/m2 (total, 200 mCi/m2) (3.7 GBq/m2; total, 7.4 GBq/m2).

摘要

目的

Lym-1是一种优先靶向恶性淋巴细胞的单克隆抗体，用碘131（¹³¹I）标记后可使非霍奇金淋巴瘤（NHL）患者获得缓解。基于总剂量分次给药的策略，本研究旨在确定相隔4周给予的最多4剂¹³¹I-Lym-1中前两剂的最大耐受剂量（MTD）和疗效。此外，还评估了毒性和辐射剂量学。

材料与方法

20例晚期NHL患者共入组21次。21次入组中有13例（62%）为弥漫大细胞组织学类型。所有患者的疾病对标准治疗耐药，平均接受过4种化疗方案。在给予Lym-1后给予¹³¹I-Lym-1，患者队列中¹³¹I的剂量从40增至100 mCi（1.5至3.7 GBq）/m²体表面积。

结果

来自身体和血液的¹³¹I对骨髓的平均辐射剂量为0.34（范围0.16至0.63）rad/mCi（0.09 mGy/MBq；范围0.04至0.17 mGy/MBq）。剂量限制性毒性为3至4级血小板减少，相隔4周给予的前两剂¹³¹I-Lym-1的MTD均为100 mCi/m²（3.7 GBq/m²）。除1例3级低血压外，非血液学毒性未超过2级。接受至少两剂¹³¹I-Lym-1治疗的14次入组中有10例（71%）以及21次总入组中有11例（52%）有反应。7例反应为完全缓解，平均持续时间为14个月。100 mCi/m²（3.7 MBq/m²）队列中的所有3次入组均完全缓解（CR）。所有有反应者在接受第一剂¹³¹I-Lym-1治疗后至少有部分缓解（PR）。