Wahl R L, Zasadny K R, MacFarlane D, Francis I R, Ross C W, Estes J, Fisher S, Regan D, Kroll S, Kaminski M S
University of Michigan Medical Center, Ann Arbor 48109-0028, USA.
J Nucl Med. 1998 Aug;39(8 Suppl):21S-27S.
Iodine-131 anti-B1 antibody radioimmunotherapy for B-cell lymphoma was previously reported to have substantial antitumor activity in B-cell non-Hodgkin's lymphoma (NHL) after failures of standard and salvage chemotherapy. In this article, the University of Michigan Phase I clinical experience is updated, with follow-up of up to 6 yr since initial treatment reported.
Thirty-four patients with CD20-expressing NHL were first studied with one or more dosimetric doses of approximately 5 mCi of 1311 anti-B1 antibody (after varying predoses of unlabeled anti-B1 antibody). They were then treated with a patient-specific radioimmunotherapeutic dose designed to deliver a specified radiation dose to the whole body of between 25 and 85 cGy. Patients were observed for toxicity and tumor response.
Seventeen (50%) patients had low-grade NHL, 9 (26%) had low-grade transformed NHL and 8 (24%) had de novo intermediate-grade NHL. At study entry, 17 (50%) had an elevated lactate dehydrogenase level, 12 (35%) had high tumor burden and 18 (53%) had not responded to their last chemotherapy. The median number of prior NHL therapies was 4.1. Twenty-eight of 34 patients completed treatment, with 22 of 28 (79%) achieving a response and 14 of 28 (50%) achieving a complete response (CR). The median duration of response was 357 days. The median duration of response for CRs was 471 days, with 4 CRs having a duration of > 1000 days (maximum = > 1460 days). Bone marrow toxicity was dose-limiting and dependent on the total-body dose (TBD) of radiation. Thrombocytopenia appeared to be more marked in patients with prior bone marrow transplantation. The TBD of 75 cGy was established as the maximum tolerated dose in patients who had not had prior bone marrow transplantation. Duration of CR was significantly longer (p < 0.04) in patients who received a TBD of 65-75 cGy (1109 days) than it was in those who received a lower TBD of 25-60 cGy (385 days). Four of 34 (12%) patients developed detectable human antimouse antibody levels. The median survival from study entry for all patients was 1508 days (range = 63 to >2226 days). Sixteen of 17 patients who achieved a response of > or = 6 mo duration remain alive.
This update of the Phase I results after 1311 anti-B1 antibody treatment for NHL indicates that CRs can be durable and that survival can be of long duration. This form of therapy for NHL should have increasing application in clinical practice after confirmation of these results in larger multicenter studies.
先前报道，碘-131抗B1抗体放射免疫疗法用于B细胞淋巴瘤，在标准和挽救性化疗失败后的B细胞非霍奇金淋巴瘤（NHL）中具有显著的抗肿瘤活性。本文更新了密歇根大学的I期临床经验，报告了自初始治疗以来长达6年的随访情况。
34例表达CD20的NHL患者首先接受一个或多个剂量约为5mCi的131I抗B1抗体的剂量测定剂量（在给予不同预剂量的未标记抗B1抗体之后）。然后用根据患者个体情况设计的放射免疫治疗剂量进行治疗，该剂量旨在向全身输送25至85cGy的特定辐射剂量。观察患者的毒性和肿瘤反应。
17例（50%）患者为低度NHL，9例（26%）为低度转化型NHL，8例（24%）为原发性中度NHL。在研究开始时，17例（50%）患者乳酸脱氢酶水平升高，12例（35%）患者肿瘤负荷高，18例（53%）患者对其最后一次化疗无反应。先前NHL治疗的中位数为4.1次。34例患者中有28例完成治疗，28例中的22例（79%）获得缓解，28例中的14例（50%）获得完全缓解（CR）。缓解的中位持续时间为357天。CR患者的缓解中位持续时间为471天，4例CR患者的持续时间>1000天（最长=>1460天）。骨髓毒性是剂量限制性的，并且取决于全身辐射剂量（TBD）。血小板减少症在先前接受过骨髓移植的患者中似乎更为明显。75cGy的TBD被确定为未接受过先前骨髓移植患者的最大耐受剂量。接受65 - 75cGy TBD的患者（1109天）的CR持续时间显著长于（p<0.04）接受25 - 60cGy较低TBD的患者（385天）。34例患者中有4例（12%）出现可检测到的人抗鼠抗体水平。所有患者从研究开始的中位生存期为1508天（范围=63至>2226天）。17例缓解持续时间≥6个月的患者中有16例仍存活。
对NHL进行131I抗B1抗体治疗后的I期结果更新表明，CR可以是持久的，生存期可以很长。在更大规模的多中心研究证实这些结果后，这种NHL治疗形式应在临床实践中得到越来越广泛的应用。
