Rajguru Saurabh, Kristinsdottir Thorhildur, Eickhoff Jens, Peterson Chris, Meyer Christine M, Traynor Anne M, Kahl Brad S
University of Wisconsin, Madison, Wisconsin.
Reykjavik, Iceland.
Clin Adv Hematol Oncol. 2014 Aug;12(8):509-15.
Yttrium 90-ibritumomab tiuxetan (90Y-IT) radioimmunotherapy has proved to be effective in relapsed follicular lymphoma (FL). We conducted a clinical trial in which 90Y-IT followed by maintenance rituximab (MR) was evaluated as initial therapy for high-tumor-burden FL.
Eligible patients had histologically confirmed FL and met the GELF (Groupe d'Etude des Lymphomes Folliculaires) criteria for high tumor burden. All patients received a single dose of 90Y-IT. Patients with platelet counts of 150,000/mm³ or higher received 0.4 mCi/kg, and patients with platelet counts between 100,000/mm³ and 149,000/mm³ received 0.3 mCi/kg. At 6 months, patients without progressive disease (PD) received rituximab weekly for 4 weeks at a dose of 375 mg/m² (consolidation therapy), followed by MR consisting of the same dose every 3 months for a planned 5 years.
From January 2005 through November 2007, a total of 16 patients were enrolled. The median age was 52 years (range, 37-75). The major toxicity from 90Y-IT was myelosuppression, with 88% and 31% of the patients experiencing grade 3 and grade 4 hematologic toxicity, respectively. The responses to 90Y-IT induction therapy were as follows: 7 patients with complete response/unconfirmed complete response (CR/Cru), 4 with partial response (PR), 3 with stable disease (SD), and 2 with progressive disease (PD). We identified 6 patients with early PD (range, 4-16 months) and 10 patients with prolonged remission (range, 37-101+ months). Compared with the patients who had prolonged remission, the patients who had early PD tended to have larger baseline nodal masses. The median progression-free survival (PFS) has not been reached after a median follow-up period of 48 months. The 3-year PFS and overall survival (OS) rates were 56% (95% CI, 37%-87%) and 93% (95% CI, 80%-100%), respectively.
The overall response rate (ORR) to 90Y-IT was 69% in patients who had previously untreated, high-tumor-burden FL, which is lower than what is observed with contemporary rituximab/chemotherapy combinations. MR after 90Y-IT did convert all PRs to CRs. Alternative therapies should be considered for patients who have FL with large nodal masses (>9 cm), whereas very durable responses are possible in patients who have intermediate-size masses (>9 cm).
钇90-替伊莫单抗（90Y-IT）放射免疫疗法已被证明对复发性滤泡性淋巴瘤（FL）有效。我们开展了一项临床试验，评估90Y-IT序贯维持利妥昔单抗（MR）作为高肿瘤负荷FL初始治疗的效果。
符合条件的患者经组织学确诊为FL，且符合高肿瘤负荷的GELF（滤泡性淋巴瘤研究组）标准。所有患者均接受单剂量的90Y-IT。血小板计数≥150,000/mm³的患者接受0.4 mCi/kg的剂量，血小板计数在100,000/mm³至149,000/mm³之间的患者接受0.3 mCi/kg的剂量。在6个月时，无疾病进展（PD）的患者接受剂量为375 mg/m²的利妥昔单抗每周1次，共4周（巩固治疗），随后进行MR，即每3个月给予相同剂量，计划持续5年。
2005年1月至2007年11月，共纳入16例患者。中位年龄为52岁（范围37 - 75岁）。90Y-IT的主要毒性为骨髓抑制，分别有88%和31%的患者发生3级和4级血液学毒性。90Y-IT诱导治疗的反应如下：7例完全缓解/未确认完全缓解（CR/Cru），4例部分缓解（PR），3例疾病稳定（SD），2例疾病进展（PD）。我们确定了6例早期PD患者（范围4 - 16个月）和10例长期缓解患者（范围37 - 101 +个月）。与长期缓解的患者相比，早期PD患者的基线淋巴结肿块往往更大。中位随访48个月后，中位无进展生存期（PFS）尚未达到。3年PFS率和总生存期（OS）率分别为56%（95%CI，37% - 87%）和93%（95%CI，80% - 100%）。
对于既往未治疗的高肿瘤负荷FL患者，90Y-IT的总缓解率（ORR）为69%，低于当代利妥昔单抗/化疗联合方案的观察结果。90Y-IT后的MR确实使所有PR患者转化为CR患者。对于有大淋巴结肿块（>9 cm）的FL患者，应考虑替代疗法，而对于中等大小肿块（>9 cm）的患者，可能会有非常持久的反应。
