Mechanism of action of isatuximab in multiple myeloma. Literature review and clinical observation

Background. Multiple myeloma (MM) is a malignant lymphoproliferative disorder characterized by tumor plasma cells infiltrating the bone marrow. The pharmaceutical industry for the treatment of MM is experiencing a boom, characterized by the emergence of new-generation targeted drugs. It is important to describe the differences in the binding pattern of monoclonal antibodies to the CD38 protein and to analyze the treatment outcomes of MM patients treated with isatuximab, depending on various biological characteristics of the disease.

Aim. To analyze the literature data on the isatuximab mechanism of action on tumor plasma cells, the features of monoclonal antibodies use depending on various factors and present a clinical observation of the isatuximab therapy in ММ patient and concomitant chronic obstructive pulmonary disease (COPD).

Materials and methods. For this review, PubMed databases, clinical trial registries, and meeting libraries were searched from inception to December 20, 2025, using the terms reflecting multiple myeloma, isatuximab, daratumumab. We analyzed publications devoted to studying the mechanism of action of CD38 monoclonal antibodies and examining the efficacy of isatuximab in the treatment of multiple myeloma, depending on various factors. Our experience with the IsaPd regimen in a patient with relapsed / refractory MM and concomitant COPD is presented.

Results. Isatuximab is the only CD38 antibody capable of inducing direct tumor cell apoptosis. The 1q abnormality did not affect survival in ММ patients treated with isatuximab-containing regimens. Due to limited complement-dependent cytotoxicity, isatuximab may be a preferred option for patients with COPD or asthma. The article describes our experience of isatuximab therapy in MM patient with COPD. The patient was diagnosed with MM in 2015 at the age of 57. Induction therapy consisted of bortezomib- and lenalidomide-containing regimens; an antitumor response was not achieved. Hematopoietic stem cell mobilization was performed after the DHAP regimen (cisplatin, cytarabine, dexamethasone) in combination with granulocyte colony-stimulating factor. To overcome resistance, therapy including carfilzomib was administered, achieving a very good partial remission. Autologous hematopoietic stem cell transplantation (melphalan 200 mg / m²) was then performed, followed by local radiation therapy to the plasmacytoma area, resulting in complete remission. Subsequently, due to relapse, therapy including ixazomib and lenalidomide was prescribed. In 2021, due to MM progression, sixth-line anti-relapse therapy with the IsaPd regimen was initiated. Despite COPD with frequent exacerbations requiring bronchodilator therapy, the patient tolerated isatuximab satisfactorily, with no adverse reactions. Twelve courses of therapy were completed, achieving partial remission.

Conclusion. Monoclonal antibodies to CD38 are being integrated into induction therapy protocols for MM patients. This article describes the isatuximab mechanism of action and presents experience using IsaPd as a sixth-line therapy in a patient with MM and COPD. Along with a favorable safety profile, we also observed high treatment efficacy.