Immune-related adverse events with bispecific T-cell engager therapy targeting B-cell maturation antigen

• Published in: Haematologica (Roma) Vol. 109; no. 1; pp. 357 - 361
• Main Authors: Piron, Bénédicte, Bastien, Mathilde, Antier, Chloé, Dalla-Torre, Romain, Jamet, Bastien, Gastinne, Thomas, Dubruille, Viviane, Moreau, Philippe, Martin, Jérôme, Bénichou, Antoine, Touzeau, Cyrille, Tessoulin, Benoît
• Format: Journal Article
• Language: English
• Published: Italy Ferrata Storti Foundation 01.01.2024; Fondazione Ferrata Storti
• Subjects: Antibodies, Bispecific; Antibodies, Bispecific - adverse effects; B-Cell Maturation Antigen; Case Report; Human health and pathology; Humans; Life Sciences; T-Lymphocytes
• ISSN: 0390-6078; 1592-8721; 1592-8721
• DOI: 10.3324/haematol.2023.282919

Immune-related adverse events with bispecific T-cell engager therapy targeting B-cell maturation antigenBispecific antibodies (BispAb) targeting BCMAxCD3 have been recently approved for the treatment of patients with relapsed and refractory myeloma previously exposed to immunomodulatory drug, proteasome inhibitor, and anti-CD38 antibodies. For instance, the phase I/II MajesTEC-1 study demonstrated high efficacy of teclistamab in advanced (median of 5 prior lines), triple-class exposed and refractory myeloma, with an overall response rate of 63% and median progression-free survival of 11.3 months. 1 In BispAb studies, most common treatment-emergent adverse events (AE) were cytokine release syndrome (CRS), hematological toxicities and immune effector cell associated neurotoxicity syndrome. Dysimmune events were neither observed nor classified as such but were exclusion criteria for protocol enrollment. 2 Immune-related adverse events (irAE) are well described for the immune checkpoint inhibitor therapy such as anti-PD1 or anti-CTLA-4. This type of AE could affect different organs, such as gastrointestinal, endocrinological, skin or rheumatological systems. 3 The explanation of these irAE under checkpoints inhibitors seems straightforward with the activity enhancement of T cells. 3 Thus, through two thoroughly documented clinical cases, we report here how dysimmunity could be induced by T-cell engaging BispAb, with very different patterns of symptoms. Case 1Case 1 is a 77-year-old woman without a significant medical history, who has been treated for IgG κ multiple myeloma. Her ninth line consisted of a CD3xBCMA BispAb, a stringent complete remission (sCR) from the 13 th cycle was obtained. A grade 1 CRS was noted at first cycle and was resolutive. Shortly after sCR, the patient presented with recurring oligoarthritis. There was a biological inflammatory syndrome (C reactive protein [CRP] increased and thrombocytosis). Blood cultures were positive twice for Neisseria cinerea, and while echocardiography showed no signs of infective endocarditis, she was treated with ceftriaxone (2 g/day) for 14 days and the oligoarthritis was resolved (Figure 1 ). The positron emission tomography-comuted tomography (PET-CT) scan that had been performed for the disease's extension showed grade 3 (the highest grade) parietal hypermetabolism of the thoracic aorta, brachiocephalic artery trunk, right subclavian artery, and left common iliac artery (Figure 2A -D, bottom row with arrows). On examination, no recent or previous cephalic, visual, mandibular, or rhizome manifestations, no chest, back, abdominal, or lumbar pain with an inflam-