Gigliotta Emilia, Plano Federica, Corsale Giusy, Corsale Anna Maria, Aquilina Cristina, Speciale Maria, Rizzuto Andrea, Martino Enrica Antonia, Leotta Dario, Solimando Antonio Giovanni, Ria Roberto, Gentile Massimo, Siragusa Sergio, Botta Cirino
Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, University of Palermo, Palermo, Italy.
Hematology Unit, Azienda Ospedaliera Annunziata, Cosenza, Italy.
Exp Hematol Oncol. 2024 Aug 6;13(1):82. doi: 10.1186/s40164-024-00547-x.
Multiple myeloma (MM) is a hematologic malignancy characterized by abnormal plasma cell proliferation in the bone marrow. Recent advancements in anti-CD38 monoclonal antibody therapies, such as daratumumab and isatuximab, have significantly improved MM patient survival. However, the lack of predictive factors of response to these therapies remains a challenge. Notably, anti-CD38 antibodies can interfere with laboratory tests, complicating response assessment. We conducted a retrospective study to evaluate the association between the appearance of positive IgGk (therapeutic antibody) on immunofixation/immunosubtraction (IF) and clinical parameters in 87 non-IgGk MM patients treated with anti-CD38 therapy. Positive IgGk IF was observed in 42 patients after a median of three treatment courses. Patients with positive IgGk IF had higher rates of complete/very good partial responses (p = 0.03) and improved progression-free survival (median not reached vs. 21.83 months, p < 0.01). High BMI (p = 0.03), higher hemoglobin (p = 0.02), lower CRP (p = 0.04), and lower monoclonal protein levels (p = 0.03) were associated with positive IgGk IF. Our findings suggest that monitoring therapeutic antibody appearance on IF may predict and optimize anti-CD38 therapy in MM. Potential explanations include the impact of patient factors (e.g. BMI) on drug pharmacokinetics, the relationship between antibody levels and immune response, and the influence of tumor biology. Further research is needed to elucidate the underlying mechanisms and clinical utility of this biomarker. Nonetheless, our results highlight the importance of considering therapeutic antibody detection when interpreting laboratory tests and managing MM patients receiving anti-CD38 therapies.
多发性骨髓瘤（MM）是一种血液系统恶性肿瘤，其特征为骨髓中异常浆细胞增殖。抗CD38单克隆抗体疗法（如达雷妥尤单抗和isatuximab）的最新进展显著提高了MM患者的生存率。然而，缺乏这些疗法反应的预测因素仍是一项挑战。值得注意的是，抗CD38抗体可干扰实验室检测，使反应评估变得复杂。我们进行了一项回顾性研究，以评估87例接受抗CD38治疗的非IgGk MM患者免疫固定/免疫扣除（IF）上阳性IgGk（治疗性抗体）的出现与临床参数之间的关联。42例患者在中位三个疗程后观察到阳性IgGk IF。阳性IgGk IF患者的完全/非常好部分缓解率更高（p = 0.03），无进展生存期改善（中位未达到 vs. 21.83个月，p < 0.01）。高BMI（p = 0.03）、较高血红蛋白（p = 0.02）、较低CRP（p = 0.04）和较低单克隆蛋白水平（p = 0.03）与阳性IgGk IF相关。我们的研究结果表明，监测IF上治疗性抗体的出现可能预测并优化MM的抗CD38治疗。潜在解释包括患者因素（如BMI）对药物药代动力学的影响、抗体水平与免疫反应之间的关系以及肿瘤生物学的影响。需要进一步研究以阐明该生物标志物的潜在机制和临床应用。尽管如此，我们的结果强调了在解释实验室检测结果和管理接受抗CD38治疗的MM患者时考虑治疗性抗体检测的重要性。
