Luskin Marlise R, Yin Jun, Lozanski Gerard, Curran Emily, Malnassy Gregory, Mrózek Krzysztof, Bloomfield Clara D, Cataland Spero R, Fulton Noreen, Kolitz Jonathan, Laplant Betsy, Kour Oudom, Powell Bayard L, Vij Ravi, Wang Eunice S, Grinblatt David, Stone Richard M, Uy Geoffrey L, Larson Richard A, Stock Wendy
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
Department of Biostatistics and Bioinformatics, Moffitt Cancer Center, Tampa, Florida, USA.
Cancer. 2025 Feb 15;131(4):e35750. doi: 10.1002/cncr.35750.
Acute lymphoblastic leukemia (ALL) in adults is aggressive, with long-term outcomes impacted by treatment resistance and toxicity. CD52 is expressed in most cases of B- and T-lineage ALL. Alemtuzumab, a humanized immunoglobulin G1 monoclonal antibody that targets CD52, was identified as a potential agent to improve treatment efficacy without increasing toxicity.
In this phase 1/2 study (Cancer and Leukemia Group B [CALGB] 10102, NCT00061945), a course of single-agent alemtuzumab was intercalated into CALGB 19802 backbone chemotherapy after the third course of intensive chemotherapy in those who were CD52+ at diagnosis. Phase 1 tested three dose levels of subcutaneous alemtuzumab (10, 20, and 30 mg 3 times weekly for 4 weeks/12 doses) and demonstrated that 30 mg was tolerable. Phase 2 established feasibility.
The study enrolled 295 evaluable patients (115 in phase 1, 180 in phase 2); 206 (69.8%) were CD52+. Among evaluable CD52+ patients, 43.7% (90/206) completed the first three treatment modules; 97.8% (88 of 90) were treated with alemtuzumab. Alemtuzumab was associated with cytomegalovirus viremia, which occurred in 23.3% (14 of 60) of patients during and 29.2% (19 of 65) after alemtuzumab treatment. With a median follow-up of 101.2 months, median overall survival (OS) was 26.3 months (3-year rate, 44%; 5-year rate, 36%; 10-year rate, 31%). Landmark analysis at the start of the fourth course of treatment demonstrated no difference in OS or disease-free survival between patients who did and who did not receive alemtuzumab.
Alemtuzumab was feasible to administer in adults with ALL receiving intensive chemotherapy, but was without evidence of benefit.
成人急性淋巴细胞白血病（ALL）具有侵袭性，长期预后受治疗耐药性和毒性影响。CD52在大多数B系和T系ALL病例中表达。阿仑单抗是一种靶向CD52的人源化免疫球蛋白G1单克隆抗体，被确定为一种在不增加毒性的情况下提高治疗疗效的潜在药物。
在这项1/2期研究（癌症与白血病B组[CALGB]10102，NCT00061945）中，对于诊断时CD52阳性的患者，在强化化疗的第三个疗程后，将单药阿仑单抗疗程插入CALGB 19802的主干化疗中。1期试验了皮下注射阿仑单抗的三个剂量水平（每周3次，每次10、20和30 mg，共4周/12剂），并证明30 mg是可耐受的。2期确定了可行性。
该研究纳入了295例可评估患者（1期115例，2期180例）；206例（69.8%）为CD52阳性。在可评估的CD52阳性患者中，43.7%（90/206）完成了前三个治疗模块；97.8%（90例中的88例）接受了阿仑单抗治疗。阿仑单抗与巨细胞病毒血症相关，在阿仑单抗治疗期间，23.3%（60例中的14例）的患者发生巨细胞病毒血症，治疗后为29.2%（65例中的19例）。中位随访101.2个月，中位总生存期（OS）为26.3个月（3年生存率44%；5年生存率36%；10年生存率31%）。在第四个疗程开始时的标志性分析表明，接受和未接受阿仑单抗治疗的患者在总生存期或无病生存期方面没有差异。
阿仑单抗用于接受强化化疗的成人ALL患者是可行的，但没有获益证据。
