Use of Teclistamab Outside of Clinical Trials in Latin America: Risk of Infections and Immunoglobulin Replacement
Authors: Pericole Fernando Vieira , Crusoe Edvan , Ribeiro Glaciano , Lima Juliana , Ottoni Erica Lammerhirt , Cunha Rafael , Costa Abel , Cury Priscilla , Maciel James , Hungria Vania 
Published: December 2024

Introduction: Teclistamab (TEC) was the first BCMA-targeting bispecific antibody (BsAb) approved. Between November 2022 and February 2023 triple-class relapsed / refractory myeloma (RRMM) patients had access to TEC through Expanded Access Program in Brazil. BCMA-targeting BsAbs trials had shown high rates of infections and, therefore, reports of TEC treatment outside clinical trials and management of its emergent toxicities are of great importance at this moment.

Methods: Participants must have been triple-class exposed/refractory, with previous therapies including any proteasome inhibitor, any immunomodulatory drug and any anti-CD38 therapy and have received at least one dose of TEC. We collected prospective data focused on response, safety and adverse events of interest, including cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity (ICANS), use of immunoglobulin (IVIG), and infections. All participants received acyclovir and trimethoprim-sulfamethoxazole during all TEC therapy. Vaccinations and IVIG replacement were indicated per institutional guidelines.

Results: We included 27 RRMM patients (pts), mostly male (60%) with a median age of 59 years (39-77yrs). All pts were triple-class exposed and over 80% triple-class refractory. The overall response rate was 48% (11% complete responses and 34% very good partial responses) and the median overall survival was 14.2 months. CRS occurred in 69% of pts, mostly grade 1 (54%), with 15% of grade 2 CRS. ICANS was rare, reported as grade 2 in 1 patient (4%). In the first three months of TEC, infections were reported in most patients (73%). Severe infections (grade 3 or higher) occurred in 5 patients (20%). Two of them died because of severe bacterial infections. Ten of 27 patients (37%) received IVIG at early phases of therapy. Post baseline IgG levels decreased rapidly, achieving levels &lt; 400mg/dL in 62% of patients. Over time, rate of patients under IVIG replacement therapy increased sharply, covering 92% of them after 6 months of TEC. Concurrently, infection rate decreased significantly, with 3 cases (11%) of grade &lt; 2 infections, mostly upper respiratory viral infections. COVID infections were not described in this cohort. Eleven patients remain alive and under TEC therapy. The most common cause of death were disease progression and refractoriness (13 patients) followed by grade 5 infections (3 patients).

Discussion: Our study focused on TEC therapy outside clinical trials and particularly its emergent adverse events. Infections were the most common side effect of this BCMA-targeting BsAb, even after COVID pandemic. Rate of patients receiving IVIG increased over time while infection rate and its severity decreased. Awareness of infection risk of TEC could change this dismal outcome, combined with preventive measures such as broad coverage vaccination, mandatory use of prophylactic antibiotics and IVIG replacement therapy for all treated patients.