Hematology Branch, National Heart, Lung, and Blood Institute, Bldg 10 CRC 4-5230, Bethesda, MD 20892, USA.
J Clin Oncol. 2010 Dec 10;28(35):5166-73. doi: 10.1200/JCO.2010.29.7010. Epub 2010 Nov 1.
Myelodysplastic syndromes (MDS) are characterized by ineffective hematopoiesis and progression to leukemia. Clinical and experimental evidence suggests an immune-mediated pathophysiology in some patients, in whom immunosuppressive therapy (IST) with horse antithymocyte globulin (h-ATG) and cyclosporine (CsA) can be effective. Because of the toxicities associated with h-ATG/CsA, we investigated an alternative regimen with alemtuzumab in MDS.
We conducted a nonrandomized, off-label, pilot, phase I/II study of alemtuzumab monotherapy in patients with MDS who were judged likely to respond to IST based on the following criteria: HLA-DR15-negative patients whose age plus the number of months of RBC transfusion dependence (RCTD) was less than 58; and HLA-DR15-positive patients whose age plus RCTD was less than 72. In total, 121 patients with MDS were screened, of whom 32 met eligibility criteria to receive alemtuzumab 10 mg/d intravenously for 10 days. Primary end points were hematologic responses at 3, 6, and 12 months after alemtuzumab.
Seventeen (77%) of 22 evaluable intermediate-1 patients and four (57%) of seven evaluable intermediate-2 patients responded to treatment with a median time to response of 3 months. Four of seven evaluable responders with cytogenetic abnormalities before treatment had normal cytogenetics by 1 year after treatment. Five (56%) of nine responding patients evaluable at 12 months had normal blood counts, and seven (78%) of nine patients were transfusion independent.
Alemtuzumab is safe and active in MDS and may be an attractive alternative to ATG in selected patients likely to respond to IST.
骨髓增生异常综合征（MDS）的特征是无效造血和向白血病进展。临床和实验证据表明，一些患者存在免疫介导的病理生理学机制，在这些患者中，马抗胸腺细胞球蛋白（h-ATG）和环孢素（CsA）的免疫抑制治疗（IST）可能有效。由于 h-ATG/CsA 相关的毒性，我们研究了 MDS 中用阿仑单抗替代方案。
我们对 MDS 患者进行了一项非随机、非标签、Ⅰ/Ⅱ期、单药阿仑单抗的试验研究，这些患者被认为根据以下标准可能对 IST 有反应：HLA-DR15 阴性患者，其年龄加红细胞输注依赖性（RCTD）月数小于 58 个月；HLA-DR15 阳性患者，其年龄加 RCTD 小于 72 个月。共筛选了 121 例 MDS 患者，其中 32 例符合接受阿仑单抗 10 mg/d 静脉输注 10 天的条件。主要终点是阿仑单抗治疗后 3、6 和 12 个月的血液学反应。
22 例可评估的中 1 组患者中有 17 例（77%）和 7 例可评估的中 2 组患者中有 4 例（57%）对治疗有反应，中位反应时间为 3 个月。治疗前有细胞遗传学异常的 7 例可评估的应答者中，有 4 例在治疗 1 年后有正常的细胞遗传学。在 12 个月可评估的 9 例应答者中，有 5 例（56%）的血细胞计数正常，9 例患者中有 7 例（78%）不再需要输血。
阿仑单抗在 MDS 中安全且有效，在可能对 IST 有反应的选择患者中，可能是 ATG 的一种有吸引力的替代方案。
