Latest in Relapsed/Refractory Amyloidosis Research: Early Results of CAR-T and Bispecific Antibody Clinical Trials

Two new treatment approaches for relapsed or refractory light chain (AL) amyloidosis were presented at the 2025 American Society of Clinical Oncology (ASCO) conference. Results were shared from the first U.S.-based clinical trial of a chimeric antigen receptor T-cell (CAR-T) therapy in AL amyloidosis and from a trial studying teclistamab, a bispecific antibody. Both therapies showed encouraging results in early studies.

CAR-T therapy NXC-20 shows full response in early trial

The NEXICART-2 study evaluated NXC-201, CAR-T therapy targeting the B-cell maturation antigen (BCMA), in patients with relapsed/refractory amyloidosis. CAR-T therapy involves modifying a patient’s immune cells to better find and eliminate abnormal plasma cells that cause AL amyloidosis.

Click the button below to watch a brief explanation from experts of what BCMA is. 

What is BCMA and why is it a good target?

Seven patients participated in the early phase of the trial. These individuals had already tried several other treatments (a median of four prior therapies) and still had active disease. Some of them had heart involvement, and some had kidney problems. After receiving NXC-201:

• All patients showed a hematologic response, meaning the abnormal proteins in their blood dropped to healthy levels.

• All except one showed minimal residual disease (MRD) negativity, indicating a very deep response with no detectable disease in the bone marrow.

• All achieved very good partial responses (VGPR) or complete responses (CR), with no relapses at the time of reporting.

• Side effects included cytokine release syndrome (CRS), a temporary immune response, and blood count drops. No patients experienced nerve-related side effects, cardiac issues, or treatment-related infections.

These early results are promising. This clinical trial is ongoing, with phase 1b/2 currently recruiting patients. 

Teclistamab: a bispecific antibody producing deep responses

In another early study, researchers evaluated teclistamab in eight patients with relapsed/refractory amyloidosis. Five patients had cardiac involvement, and all had received at least three prior lines of therapy. 

After receiving teclistamab: 

• 100% had a hematologic response, with 7 achieving a complete response and 1 achieving a very good partial response.
• Two patients had heart side effects and one had kidney side effects.
• Side effects included two serious reactions (a temporary spike in liver enzymes and low platelets), but these were managed and resolved.
• Two patients experienced low-grade cytokine release syndrome.

One patient had a complete response after only a single dose, with no further treatment needed for over seven months. No relapses or deaths were reported during the follow-up.

The early results show that teclistamab may be effective in patients with AL amyloidosis who have tried many different options. More research is needed to test this treatment for AL amyloidosis.

What these developments mean for patients

Both studies offer insights into possible treatments for patients with relapsed or refractory amyloidosis, who currently have no approved treatments after standard therapies fail. Although they are in early stages, and need more development to be officially approved, these results are promising. 

For patients, these updates highlight the possibility of more targeted therapies that go beyond traditional approaches used for multiple myeloma, which have been the mainstay in amyloidosis care. New trials will help determine how broadly these therapies can be used and whether their effects last over time.

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Sources: 

• Safety and efficacy data from Nexicart-2, the first US trial of CAR-T in R/R light chain (AL) amyloidosis, Nxc-201.
• Teclistamab in relapsed/refractory systemic AL amyloidosis.