This study presents the first real-world evidence of efficacy and safety of the BCMA-targeted bispecific antibody teclistamab in patients with relapsed/refractory systemic light-chain amyloidosis (AL). Despite prior multi-line treatment failures and progressive organ dysfunction, teclistamab achieved rapid and sustained hematological remission with favorable tolerability, offering novel therapeutic insights for this challenging patient population.
Literature Overview
The article titled 'Safety and efficacy assessment of teclistamab in relapsed/refractory amyloidosis: a case study', published in Frontiers in Oncology, retrospectively analyzes clinical responses and safety profiles of teclistamab in AL amyloidosis patients after multi-line therapy failure. The study highlights that while current AL treatments face limitations including high recurrence rates and progressive organ deterioration, teclistamab - a BCMA-targeted bispecific antibody - has demonstrated remarkable efficacy in relapsed/refractory multiple myeloma but lacks clinical evidence in AL amyloidosis. This case report fills this critical knowledge gap, providing clinicians with a potential therapeutic option.
Background Knowledge
Systemic light-chain amyloidosis (AL) is a rare plasma cell disorder characterized by misfolded immunoglobulin light chains depositing in vital organs (heart, kidneys, liver, nervous system), causing progressive organ dysfunction. Current standard regimens combining daratumumab, bortezomib, and dexamethasone still face challenges with relapse and drug resistance. Bispecific antibodies like teclistamab engage CD3+ T cells and BCMA+ plasma cells to activate cytotoxic T cell responses. While extensively studied in multiple myeloma, evidence for AL applications remains limited. This case demonstrates rapid hematological response and cardiac improvement with teclistamab in refractory AL, though multi-center validation remains necessary.
Research Methods and Experiments
This study reports a 64-year-old male patient diagnosed with AL amyloidosis presenting with progressive renal and cardiac dysfunction. Following treatment failure with daratumumab, bortezomib, and dexamethasone regimens, the patient was transitioned to teclistamab therapy. Dynamic changes in hematological response (lambda FLC), cardiac function (NTproBNP), renal parameters (serum creatinine, proteinuria), and treatment-emergent adverse events were systematically evaluated.
Key Conclusions and Perspectives
Research Significance and Prospects
This real-world case series provides initial evidence supporting BCMA-targeted bispecific antibody therapy for AL amyloidosis. While demonstrating promising hematological and cardiac benefits, the lack of renal response suggests possible combination strategies with organ-protective agents may be necessary. Future multi-center trials should establish optimal dosing, identify responsive patient subgroups, and evaluate combination regimens to improve organ response rates, thereby offering clinicians evidence-based therapeutic options.
Conclusion
Systemic light-chain amyloidosis (AL) represents a severe plasma cell disorder causing multi-organ dysfunction with limited treatment options. This case report demonstrates that teclistamab - a BCMA-targeted bispecific antibody - can achieve rapid hematological remission and cardiac improvement in patients refractory to standard therapies, with favorable safety profile. The absence of renal recovery highlights the need for combination approaches targeting organ protection. These findings warrant larger clinical trials to comprehensively evaluate teclistamab's efficacy, safety, and optimal combination strategies in AL amyloidosis.
