Teclistamab induced rapid and deep hematologic response in relapsed/refractory light chain amyloidosis: A multicenter retrospective study

Abstract

Abstract Objective: Daratumumab-based therapy has significantly improved the prognosis of patients with light chain (AL) amyloidosis. However, treatment options are limited for patients with a suboptimal response to first-line daratumumab therapy, as well as for those with relapsed/refractory (R/R) disease after multiple lines of therapy. We aim to explore the efficacy and safety of the bispecific T-cell engager antibody, teclistamab in daratumumab-exposed R/R AL amyloidosis. Methods: This study retrospectively included patients with R/R AL amyloidosis who received at least one dose of teclistamab between October, 2024, and May, 2025, at five university hospitals in China. Teclistamab was administered subcutaneously, with a step-up dosing regimen: 0.06 mg/kg on day 1, 0.3 mg/kg on day 3, and 1.5 mg/kg or 60 mg fixed dose on day 5, followed by weekly administration of 1.5 mg/kg or 60 mg fixed dose. The treating physician adjusted the frequency of teclistamab based on hematologic efficacy, gradually reducing from weekly to every 2 months. We performed statistical analysis of patients' hematologic and organ response, and adverse events. The event-free survival (EFS) of prior treatments was defined as the time from the start of treatment to disease progression, death, or the switch to the next line of therapy. The last date of follow-up for this report was July 31st, 2025. Results: A total of 18 patients were enrolled in the study, with a median age of 66 years (range 35–75). The male-to-female ratio was 7:11. Cardiac involvement was seen in all 18 patients (100%), renal involvement in 11 (61.1%) and liver involvement in 1 (5.6%). At diagnosis, 5 patients (27.8%) had t(11;14), and 4 patients (22.2%) had 1q21 amplification. The median number of prior treatment lines was 2 (range 1–5). All patients had previously received daratumumab and bortezomib, 3 t(11;14)-positive patients and 1 t(11;14)-negative patient had received venetoclax, 8 patients had used IMiDs, and 1 patient underwent ASCT. None of the patients had previously used anti-BCMA treatment. The median EFS of prior daratumumab-based treatment was 13.5 months. Regarding hematologic efficacy of daratumumab, 7 patients (38.9%) achieved ≥ VGPR. The median EFS of the last-line therapy prior to initiating teclistamab treatment was 7.6 months. Nine patients (50%) initiated teclistamab due to disease progression, while the remaining patients was refractory to prior treatment. At the time of teclistamab treatment, 12 patients (66.7%) were at Mayo stage II, 2 patients (11.1%) at stage IIIA, and 4 patients (22.2%) at stage IIIB. The median NT-proBNP level was 3260 ng/L (range 422–34,073), and the median dFLC was 101.7 mg/L (range 4.9–6133.1). At the last follow-up, patients had received a median of 4 cycles of teclistamab. Except for one patient in stage IIIB who died early, the remaining 17 patients (94.4%) achieved stringent dFLC remission, with a median time to stringent dFLC remission of 19 days (range 7–125). There was no significant difference in the time to stringent dFLC remission between patients with pre-treatment dFLC ≥180 mg/L and those with dFLC <180 mg/L. There was also no significant difference in the time to stringent dFLC remission between the 1.5 mg/kg dose group and the fixed-dose (60mg) group. Fifteen patients (83.3%) achieved CR, with a median time to CR of 21 days (range 7–87). Thirteen patients (72.2%) achieved cardiac remission, with CR, VGPR, and PR rates of 11.1%, 16.7%, and 44.4%, respectively, and a median time to cardiac response of 49 days (range 14–125). Four patients (36.4%) achieved renal remission, with CR in 9.1%, PR in 27.3%, and a median time to renal response of 28 days (range 18–88). The median follow-up was 4.5 months. One stage IIIB patient died early within a month due to cardiac progression, another patient died of pulmonary infection, while the remaining patients are still receiving teclistamab treatment. Ten patients (55.6%) experienced CRS, all of which were grade 1–2. One patient developed grade 1 ICANS. Eight patients (44.4%) had infections, 4 of which were grade 3-5. Conclusion: Teclistamab can rapidly induce high-quality hematologic response and early cardiac response in R/R AL amyloidosis. In real-world practice, fixed-dose administration and reducing the frequency of treatment based on efficacy as soon as possible is a feasible strategy and may reduce adverse events like infections.