IODINE ANTI B1 MURINE RADIOIMMUNOTHERAPY FOR CHEMOTHERAPY LYMPHOMA

二期 45例低度恶性或转化的低度恶性B细胞NHL患者 在7个中心用Bexxar（Coulter Pharmaceutical）治疗，一种碘-131- 针对B细胞上CD 20抗原的标记鼠单克隆抗体。 患者接受单次剂量测定剂量（450 mg未标记抗B1 i. v. 1小时，随后35 mg放射性标记的4 mCi I-131，持续=小时）， 然后在接下来的时间里接受周期性的伽马相机扫描和/或Nal探针计数， 7天扫描和/或探针数据用于计算所需的活性 (mCi)的I-131以递送所需的治疗剂量的辐射（cGy）。这 在剂量测定剂量后7至14天给予治疗剂量， 由与35 mg剂量相同的未标记和标记抗体剂量组成 标记有足够的I-141以递送指定的全身剂量（MTD 在之前的I期试验中确定），对于100，000- >= 150，000的患者为149，999血小板/mm 3和75 cGy。患者 入组研究前接受过大量化疗：中位既往 不同方案= 4（范围，1-8）。所有人的蒽环类药物或 含蒽二酮的方案，并在治疗后1年内复发 完成末次化疗方案（根据方案）。其他 特征包括：平均年龄= 51岁，组织学（低度恶性76%，转化 体积大者占42%。36例患者接受75 cGy，9例接受65 cGy cGy全身剂量：平均放射性= 88 mCi（范围45-177）。45个中的27个 (60 45例患者中12例（27%）有反应（PR + CR），12例（27%）有完全反应（CR）。 CR的中位持续时间尚未达到（范围为4.5至13.6+个月）， 中位随访时间为10个月，8/12例患者持续CR。 七 11例（64%）转化型NHL患者缓解，5/11例（45%）达到CR。 19例巨大病灶患者中有12例（63%）缓解（13% CR）。的 主要毒性是血液学：ANC < 100/mm 3 = 4%血小板计数< 10，000/mm3 = 11%。最低点通常发生在第5-6周， 周8-9。还观察到一过性轻度至中度非血液学毒性 最常见的事件是疲劳、恶心和发烧。45个中没有一个 患者发生HAMA。这些结果在患者预后不良的因素 表明Bexxar是一种有前途的治疗低品位和 转化为低度恶性NHL III期 碘-131托西莫单抗是放射性标记的鼠IgG 2a单克隆抗体， 对抗B细胞上的CD 20抗原60例患者在8个研究中心入组， 这项III期研究旨在比较 患者末次化疗方案和碘-131托西莫单抗。 36例（60%）患者为低度恶性NHL，23例（38%）患者为低度恶性转化NHL， 1例（2%）为中度NHL。患者必须接受≥ 2次 既往接受过化疗方案，并且必须对化疗无效或进展 最后一次化疗后6个月内。基线患者 特征是：>60岁（45%），男性（63%），诊断的中位时间 (54月），LDH升高（46%），淋巴结>= 5 cm。(54%）， 既往化疗（4）。患者接受SSKI或Lugol溶液， >=剂量测定剂量前24小时，并在剂量测定剂量后持续14天 治疗剂量患者接受单次剂量测定剂量（450 mg 在1小时内注射35 mg抗体IV，然后用5 mCi的放射性标记的 碘-131超过=小时），然后至少使用3台全身伽马照相机 在接下来的7天内获得的计数。伽马相机计数用于 计算递送所需治疗剂量所需的活性（mCi） (65 cGy是血小板1000，001的特定估计全身剂量 - 149，999和75 cGy（血小板>= 150，000）。单次治疗剂量（450 10 mg未标记的抗体IV，持续1小时，随后35 mg放射性标记的 在剂量测定剂量后7-14天施用抗体（超过2小时）。一个 60例患者中有17例（28%）观察到经评估的缓解， 他们的最后一次化疗方案相比，40/60（67%）的患者， 碘-131托西莫单抗（p=0.000008; McNemar检验）。作出完整的答复 在末次化疗方案后的2例患者中观察到， 碘-131托西莫单抗治疗后10例（17%）。在那些患有 不相等的响应持续时间（即，反应持续时间> 30天 不同），19%的人在最后一次治疗后反应持续时间较长 化疗方案和81%的反应持续时间较长， 碘-131托西莫单抗（p=0.0002; McNemar检验）。响应结果是 目前正在接受由一个独立的盲态随机放射科进行的审查， 肿瘤学审查（MIRROR）小组;将提供这些结果。校长 血液学毒性：ANC< 100 = 2%，血小板<10，000 = 2%。最低点 通常在第5-6周发生，在第8-9周恢复。一过性，轻度至 中度非血液学毒性也是最常见的事件 疲劳发烧和恶心3例（5%）患者变为HAMA阳性 治疗后。这些结果证实了早期的数据，并表明， 碘-131托西莫单抗是一种安全有效的治疗 低度和转化的低度NHL。

Phase II Forty-five patients with low-grade or transformed low-grade B-cell NHL were treated at 7 centers with Bexxar (Coulter Pharmaceutical), an iodine-131- labeled murine monoclonal antibody directed against the CD20 antigen on B cells. Patients received a single dosimetric dose (450 mg of unlabeled anti-B1 i.v. over 1 hour followed by 35 mg radiolabeled with 4 mCi I-131 over = hour) and then underwent periodic gamma camera scans and/or Nal probe counts over the next 7 days. Scan and/or probe data were used to calculate the required activity (mCi) of I-131 to deliver a desired therapeutic dose of radiation (cGy). This therapeutic dose was administered 7 to 14 days after the dosimetric dose and consisted of the same unlabeled and labeled antibody doses with the 35 mg dose labeled with enough I-141 to deliver a specified total body dose (a MTD determined in a prior phase I trial) of 65 cGy for patients with 100,000 - 149,999 platelets/mm3 and 75 cGy for patients with >=150,000. Patients had been heavily pretreated with chemotherapy prior to study entry: median prior different regimens = 4 (range, 1-8). All had failed an anthracyline or anthracenedione-containing regimen and had relapsed within 1 year after completion of their last chemotherapy regimen (as per protocol). Other characteristics included: mean age = 51, histology (low-grade 76%, transformed 24%) bulky disease 42%. Thirty-six patients received 75 cGy and 9 received 65 cGy total body dose: mean activity = 88 mCi (range 45-177). Twenty-seven of 45 (60%) patients responded (PR + CR) and 12/45 (27%) had a complete response (CR). The median duration of CR has not been reached (range 4.5 to 13.6+ months) with a median follow-up of ten months and 8/12 patients have ongoing CRs. Seven of 11 (64%) patients with transformed NHL responded and 5/11 (45%) had a CR. Twelve of 19 (63%) patients with bulky disease responded (13% CR). The principal toxicity was hematologic: ANC < 100/mm3 = 4% platelet count < 10,000/mm3 = 11%. The nadir typically occurred at week 5-6 with recovery by week 8-9. Transient mild to moderate non-hematologic toxicity was also observed with the most frequent events being fatigue, nausea, and fever. None of the 45 patients developed HAMA. These results in patients with poor prognostic factors indicate Bexxar to be a promising new agent for the treatment of low-grade and transformed low-grade NHL. Phase III Iodine-131 tositumomab is radiolabeled murine IgG2a monoclonal antibody directed against the CD20 antigen on B-cells. Sixty patients were enrolled at 8 sites in this phase III study designed to compare the efficacy outcomes between the patients' last chemotherapy therapy regimen and iodine-131 tositumomab. Thirty-six (60%) patients had low-grade NHL, 23 (38%) had transformed low-grade NHL, and 1 (2%) had intermediate grade NHL. Patients had to have received >= 2 prior chemotherapy regimens and had to have failed to respond to or progressed within 6 months of their last chemotherapy regimen. Baseline patient characteristics were: >60 years (45%), male (63%), median time from diagnosis (54 months), elevated LDH (46%), lymph node >= 5 cm. (54%), median number of prior chemotherapies (4). Patients received SSKI or Lugol's solution beginning >= 24 hours before the dosimetric dose and continuing for 14 days after the therapeutic dose. Patients received a single dosimetric dose (450 mg of antibody IV over 1 hour followed by 35 mg of antibody radiolabeled with 5 mCi of Iodine-131 over = hour) and then had a minimum of 3 whole body gamma camera counts obtained over the next 7 days. The gamma camera counts were used to calculate the required activity (mCi) to deliver the desired therapeutic dose (65 cGy which is the specific estimated whole body dose, for platelets 1000,001 - 149,999 and 75 cGy for platelets >=150,000). The single therapeutic dose (450 mg of unlabeled antibody IV over 1 hour followed by 35 mg of radiolabeled antibody over = hour) was administered 7-14 days after the dosimetric dose. An investigator-assessed response was observed in 17 of 60 (28%) patients following their last chemotherapy regimen compared to 40 of 60 (67%) patients following Iodine-131 tositumomab (p=0.000008; McNemar's test). A complete response was observed in 2 (3%) patients following their last chemotherapy regimen compared with 10(17%) following Iodine-131 tositumomab. Of the patients having nonequivalent duration of response (i.e., durations of response > 30 days different), 19% had a longer duration of response following their last chemotherapy regimen and 81% had a longer duration of response following Iodine-131 tositumomab (p=0.0002; McNemar's test). The response outcomes are currently undergoing review by a Masked Independent Randomized Radiology and Oncology Review (MIRROR) Panel; these results will be presented. The principal toxicity was hematologic; ANC< 100 = 2%, platelets < 10,000 = 2%. The nadir typically occurred at week 5-6 with recovery by week 8-9. Transient, mild to moderate nonhematologic toxicity also occurred with the most frequent events being fatigue, fever, and nausea. Three (5%) patients became HAMA positive following treatment. These results confirm earlier data and indicate that iodine-131 tositumomab is a safe and effective new agent for the treatment of low-grade and transformed low-grade NHL.