Teclisito: Low-intensity teclistamab in the outpatient setting for Relapsed/Refractory multiple myeloma

Abstract

Abstract Introduction Bispecific antibodies targeting BCMA have transformed MM management, albeit access in low- and middle-income countries (LMICs) remains limited due to economic and infrastructural barriers. The MajesTEC-1 trial established the efficacy of teclistamab, an anti-BCMA/CD3 bispecific antibody in relapsed/refractory MM (R/RMM) at 1.5 mg/kg, however 0.72 mg/kg were also highly active. Thisstudy evaluated the feasibility, safety, and efficacy of low-dose outpatient teclistamab in R/RMM persons with MM and no access to alternative therapies. Methods This prospective, single-center, non-randomized, compassionate use program was conducted between October 2023 and June 2025. Eligible patients had active R/RMM without private health insurance or access to alternative standard-of-care treatments. All patients received low-dose teclistamab (0.7 mg/kg) after conventional step-up dosing, and administered weekly in the outpatient setting and continued until a complete response (CR) with negative MRD by flow cytometry was achieved. Vial sharing between patients was allowed and prepared under sterile conditions. The primary endpoint was response after cycle 2. Secondary endpoints were progression free survival (PFS) overall survival (OS), duration of response (DOR), and safety graded per CTCAE v5.0. Results A total of 23 R/RMM patients were enrolled. The median age was 68 years (range, 49–84), 39% aged ≥70 years and 52% female. ECOG performance status was 0-1 in 65% and ≥2 in 35%. High-risk cytogenetics were present in 9%; in the remainder cytogenetic data were unavailable. Extramedullary disease was identified in 9% at baseline. Patients had received a median of 3 prior therapy lines (range, 2–10); 74% had ≥3 prior lines. Triple-refractory disease was observed in 35% and penta-refractory in 16%. Prior autologous stem cell transplant (ASCT) had been performed in 57%. The ORR was 91%, with 52% complete responses (CR), 13% stringent CR (sCR), 9% very good partial responses (VGPR), and 17% partial responses (PR). Two patients (9%) did not respond. Median time to first response was 1.5 months (range, 0.9–2.7), with 74% achieving a response after the first cycle. Five patients experienced disease progression, with a median time to progression of 7.1 months (range, 1.6–15). 14 of 23 remain free of progression. AEs occurred in 96% of patients. CRS developed in 65%, predominantly grade 1 (56%). One patient experienced ICANS. Hypogammaglobulinemia (<500 mg/dL) occurred in 70%; all received IVIG. Infections included pneumonia (30%), upper respiratory tract infections (26%), urinary tract infections (4%), bloodstream infections (4%), and gastroenteritis (13%). Hospitalization due to AEs occurred in 35%; 9% required ICU admission. Grade 3 neutropenia was observed in one patient. No deaths were associated with adverse events. PFS at 12 months was 71%, median PFS was 12 months (95% CI 6.4-17.7). The estimated 12-month OS rate was 80.8% median NR. Triple-refractory patients had significantly worse OS compared to non-triple-refractory (100%) (p=0.025). At a median follow-up of 6.1 months (range, 0.3–16.9), Conclusions TECLISITO demonstrates that low-dose, outpatient teclistamab is a feasible and effective option for R/RMM patients lacking conventional treatments. The safety profile was manageable, though infections secondary to hypogammaglobulinemia were frequent. This strategy allows for more affordable time-limited therapy that bridges therapeutic gaps for MM patients in LMICs.