Blood | Application of Elranatamab in Relapsed and/or Refractory AL Amyloidosis

This study evaluated the safety and efficacy of Elranatamab in patients with relapsed and/or refractory immunoglobulin light-chain (AL) amyloidosis, demonstrating an overall hematologic response rate of 100% and a complete response rate of 67%, providing new treatment options for high-risk patients.

 

Literature Overview

The article, titled 'Safety and Efficacy of Elranatamab in Patients with Relapsed and/or Refractory AL Amyloidosis,' published in the journal Blood, reviews and summarizes the clinical application and efficacy of Elranatamab in patients with relapsed/refractory AL amyloidosis. The study shows that Elranatamab can rapidly and deeply reduce involved free light chain (iFLC) levels during treatment, thereby improving organ function and quality of life.

Background Knowledge

Immunoglobulin light-chain (AL) amyloidosis is a rare systemic disease caused by abnormal proliferation of plasma cells, characterized by deposition of immunoglobulin light chains in multiple organs, leading to progressive organ dysfunction. The treatment goal is to rapidly and deeply reduce iFLC levels to maximize the chances of organ function recovery. Currently, there are no FDA-approved specific therapies for patients with relapsed and/or refractory AL amyloidosis (RRAL). BCMA (B-cell maturation antigen)-targeting bispecific T-cell engager (BiTE) antibodies such as Elranatamab and Teclistamab have shown favorable efficacy and safety profiles in relapsed/refractory multiple myeloma (RRMM). However, there is still a lack of large prospective study data for AL amyloidosis. This study is the first clinical evaluation of Elranatamab in RRAL patients, providing real-world treatment experience with this drug.

 

 

Research Methods and Experiments

This retrospective cohort analysis included 9 RRAL patients treated with Elranatamab monotherapy. Hematologic and organ responses were evaluated based on international consensus criteria. All patients were treated at DFCI/BWH or CUMC, following the drug's prescribing information, including an initial dose-escalation strategy and inpatient management. The study also assessed the incidence and management of cytokine release syndrome (CRS) and immune cell-associated neurotoxicity syndrome (ICANS).

Key Conclusions and Perspectives

• Elranatamab demonstrated an overall hematologic response rate of 100% in RRAL patients, with 89% achieving ≥VGPR (very good partial response) and 67% achieving complete response (CR).
• All evaluable patients showed a deep reduction in iFLC levels within the first treatment cycle, with a median time to response of 9 days.
• Among 5 evaluable patients, all achieved MRD (minimal residual disease)-negative status, indicating high activity in eliminating abnormal plasma cells.
• Elranatamab-related toxicities were mainly cytokine release syndrome (CRS) in 67% of patients and ICANS in 11%, but most were low-grade and manageable, with only one case of grade 3 CRS.
• While two patients died due to organ failure, the remaining patients maintained hematologic remission, highlighting Elranatamab's significant efficacy in controlling plasma cell disease.

Research Significance and Prospects

This study provides initial evidence for the use of Elranatamab in RRAL patients, supporting further prospective studies to confirm its efficacy and safety. The research team suggests that Elranatamab may become an important treatment option for high-risk, transplant-ineligible RRAL patients, particularly under multidisciplinary management. Future studies should focus on long-term follow-up data, including infection risk, mechanisms of resistance, and optimization of combination therapy strategies.

 

 

Conclusion

Elranatamab demonstrates highly effective hematologic responses in patients with relapsed and/or refractory AL amyloidosis, including high MRD-negative rates, rapid iFLC reduction, and improved organ responses. Although the incidence of CRS and ICANS is relatively high, most cases are low-grade and manageable. The study highlights the feasibility of using Elranatamab in high-volume amyloidosis centers but emphasizes the need for further prospective studies to evaluate long-term efficacy and safety. Cyagen Biosciences offers related gene-edited mouse models and disease research platforms to support preclinical studies of AL amyloidosis and BCMA-targeted therapies.

 

Pedro Vianna, Rajshekar Chakraborty, Shahrier Hossain, Jacob Laubach, and Giada Bianchi. Safety and efficacy of elranatamab in patients with relapsed and/or refractory immunoglobulin light-chain amyloidosis. Blood.