Real-world outcomes of teclistamab in triple-exposed relapsed/refractory multiple myeloma: Brazilian single-center experience

Abstract

Abstract Background: Teclistamab is a B-cell maturation antigen (BCMA)-targeting bispecific T-cell engager approved for commercialization in Brazil in July 2023 for patients with relapsed/refractory multiple myeloma (RRMM) who have received at least a proteasome inhibitor (PI), an immunomodulatory drug (IMiD), and an anti-CD38 monoclonal antibody. In this retrospective study, we describe a real-world initial experience with teclistamab at a Brazilian single center. Methods: We retrospectively analyzed all patients with RRMM treated with teclistamab at our institution. Overall (OS) and progression-free (PFS) survivals were estimated with Kaplan-Meier method, and progression and non-relapse mortality (NRM) were estimated with cumulative incidence curves. When not reached in a reasonable time compatible with the median follow-up, median OS or PFS were estimated with a parametric lognormal survival model. Results: We included 19 patients with a median follow-up of 16 months. The mean age was 70.4 years (SD=11.7) and 43% had high-risk cytogenetics (62% Double/Triple-hit) by mSMART criteria. The median number of prior therapy lines was 4 (47% had 2–3 lines; 32%, 4–5; 21%, ≥6). Extramedullary disease was present in 40% at teclistamab initiation. All patients had been exposed to a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody and none had been previously exposed to other BCMA-directed therapy. Monthly intravenous immunoglobulin (IVIG) replacement is part of the institutional protocol for patients treated with BCMA-targeting bispecific antibodies. At 12 months, overall survival (OS) was 78% (95% CI, 61–100%) and progression-free survival (PFS) was 67% (95% CI, 48–93%), with an estimated median PFS of 33 months. Relapse/progression at 12 months occurred in 23%, and non-relapse mortality (NRM) was 11%, all within the first month of therapy. A trend toward inferior outcomes was observed with increasing prior therapy lines (HR 1.32 per line; 95% CI, 0.97–1.80; p=0.08). Of the 17 patients available for response assessment, 81% achieved at least a very good partial response, with 69% of these achieving a stringent complete response, while the remaining 31% did not undergo bone marrow evaluation; 6% had a partial response; and 13% experienced progressive disease. Cytokine release syndrome (CRS) occurred in 62% (39% grade 2–4; 23% grade 3–4), with 93% receiving tocilizumab. One patient developed grade 4 ICANS; another was unassessable due to mechanical ventilation. One case of hemophagocytic lymphohistiocytosis was reported. Overall, 68% experienced immune effector cell-associated adverse events. Discussion: Our results show encouraging overall survival and progression-free survival outcomes in a group of patients with progression to multiple previous lines, who received treatment with teclistamab. In our study, which included only triple-exposed patients, with a median of 4 previous lines, we observed a 1-year PFS rate of 78% and an estimated median PFS of 34 months. This compares favorably with the pivotal trial (PMID: 35661166), which reported a 1-year PFS of about 45% and a median PFS of only 11 months. This may be related to the incorporation of teclistamab in earlier lines of triple-exposed patients. Since proteasome inhibitors, anti-CD38 antibodies, and immunomodulatory agents are approved for upfront therapy, patients with triple-exposed multiple myeloma are being identified earlier and real-world data validation of good outcomes with biespecific drugs in this scenario is imperative. Our real-world adverse events profile was consistent with that reported in the pivotal trial, but it remains concerning.Notably, severe events occurred predominantly in patients with high tumor burden, highlighting the need for heightened vigilance in this population, which is often underrepresented in clinical trials. The main limitations of our study are its retrospective nature and the relatively small sample size. Future studies should focus on strategies to reduce toxicity. In summary, we have demonstrated that early treatment with teclistamab results in excellent outcomes, suggesting that this drug could be integrated into earlier lines of therapy.