Department of Pathology, Duke University Medical Center, Durham, NC, USA.
Department of Pharmacy, Duke University Medical Center, Durham, NC, USA.
Clin Biochem. 2024 May;127-128:110761. doi: 10.1016/j.clinbiochem.2024.110761. Epub 2024 Mar 31.
Some therapeutic monoclonal antibodies, like daratumumab and elotuzumab, produce interfering monoclonal bands on serum protein electrophoresis (SPEP) and immunofixation electrophoresis (IFE). Whether other common therapeutic antibodies also produce interference has not been systematically evaluated.
SPEP/IFE from patients receiving isatuximab (48 patients), belantamab mafodotin (BM; 41), and denosumab (41) were retrospectively reviewed for therapeutic antibody interference. Cases exhibiting isatuximab interference were quantified and the maximum duration of isatuximab effect was evaluated. To characterize band position, neat human serum was spiked with BM or denosumab at supratherapeutic concentrations. Band migration patterns were compared on SPEP and IFE, with band position expressed relative to other constant protein fractions.
Isatuximab-induced IFE interference was common (81.3 % of evaluated patients) with a maximum observed duration of 8 weeks. 10.4 % of isatuximab patients had IgG kappa monoclonal gammopathies that co-migrated with the drug; this subset could benefit from HYDRASHIFT 2/4 isatuximab testing. 8.3 % of IFE cases were negative for an isatuximab band but showed large, endogenous M-spikes migrating elsewhere. All patients in this group expired within 1 year of this finding. We hypothesize that an inability to detect isatuximab in this setting corresponds to a large residual myeloma burden that reduces isatuximab serum concentration. This observation may serve as a negative prognostic factor. Spiking studies demonstrated that BM and denosumab produce interference in vitro, but sustained interference was not observed in >40 treated patients.
Therapeutic antibody interference in patients receiving isatuximab is common, and can persist for at least 8 weeks after administration. >10 % of patients receiving isatuximab may benefit from HYDRASHIFT testing post-therapy. In contrast, BM and denosumab fail to produce sustained interference in treated patients.
一些治疗性单克隆抗体，如达妥木单抗和埃罗妥珠单抗，在血清蛋白电泳（SPEP）和免疫固定电泳（IFE）中产生干扰性单克隆带。其他常见的治疗性抗体是否也会产生干扰尚未得到系统评估。
回顾性分析了接受伊沙妥昔单抗（48 例）、贝兰他单抗mafodotin（BM；41 例）和地舒单抗（41 例）治疗的患者的 SPEP/IFE，以评估治疗性抗体干扰。对出现伊沙妥昔单抗干扰的病例进行定量，并评估伊沙妥昔单抗作用的最长持续时间。为了描述条带位置，在超治疗浓度下将 BM 或地舒单抗直接加入到纯人血清中。比较 SPEP 和 IFE 上的条带迁移模式，并将条带位置相对于其他恒定蛋白分数表示。
伊沙妥昔单抗诱导的 IFE 干扰很常见（81.3%的评估患者），最长观察持续时间为 8 周。10.4%的伊沙妥昔单抗患者存在与药物共迁移的 IgG κ型单克隆丙种球蛋白病；这部分患者可能受益于 HYDRASHIFT 2/4 伊沙妥昔单抗检测。8.3%的 IFE 病例对伊沙妥昔单抗条带呈阴性，但显示出较大的、迁移到其他地方的内源性 M-峰。该组中所有患者在发现该结果后 1 年内均死亡。我们假设，在这种情况下无法检测到伊沙妥昔单抗对应于大量残留的骨髓瘤负担，从而降低伊沙妥昔单抗的血清浓度。这种观察结果可能是一个负预后因素。加标研究表明，BM 和地舒单抗在体外产生干扰，但在>40 例接受治疗的患者中未观察到持续干扰。
接受伊沙妥昔单抗治疗的患者中，治疗性抗体干扰很常见，且在给药后至少 8 周内仍持续存在。>10%的接受伊沙妥昔单抗治疗的患者可能在治疗后受益于 HYDRASHIFT 检测。相比之下，BM 和地舒单抗在接受治疗的患者中未产生持续的干扰。
