Lee Shares Early Data on Linvoseltamab in R/R AL Amyloidosis, Calls Responses ‘Unprecedented’

Systemic light chain (AL) amyloidosis, a life-threatening condition that starts in the bone marrow and causes damage to vital organs, lacks approved therapies once patients relapse. But there’s hope that could change, based on interest from the packed room during the May 29, 2026, hematology session at the American Society of Clinical Oncology Annual Meeting.

Hans C. Lee, MD, director of myeloma research at Sarah Cannon Research Institute in Nashville, Tennessee, presented data from the first 20 patients treated with linvoseltamab (Lynozyfic; Regeneron) in the phase 1/2 LINKER-AL2 study (NCT06292780). The phase 1 dose-escalation portion of the study, which will enroll up to 60 patients, is evaluating 2 doses of the drug in this rare disease. So far, all but 2 patients across both doses studied—80 mg and 240 mg—have had a hematologic complete response (CR). The others, both at the 80-mg dose, had very good partial responses.¹

Linvoseltamab is a bispecific B-cell maturation antigen–directed CD3 T-cell engager already approved to treat adults with relapsed or refractory multiple myeloma who have received at least 4 prior lines of therapy. It is being studied as early as the first line of treatment in myeloma.

Systemic AL amyloidosis occurs when clonal plasma cells cause protein fragments to form “chains,” depositing misfolded amyloid fibrils in vital organs and creating damage, especially to the heart and kidneys. Because of the toll the disease takes on the body, treatments must be more than effective, Lee explained. “Not only do we need deep responses,” he said, “We need rapid responses.”

In frontline treatment for AL amyloidosis, the standard of care is a combination regimen of daratumumab, cyclophosphamide, bortezomib (Velcade), and dexamethasone (Dara-VCd). This therapy targets the underlying plasma cells in the bone marrow to halt the production of the abnormal amyloid-forming proteins. But for patients who relapse, there are no FDA-approved therapies, Lee told the audience.

Why linvoseltamab? “We hypothesize that linvoseltamab would be an attractive approach for treatment of light chain amyloidosis,” Lee said, “given the rapid reduction of light chains observed with T-cell–redirected plasma cell killing with bispecific antibodies in the context of multiple myeloma.”

Early Look Shows Strong Responses

Lee’s presentation followed results for a phase 3 trial of anselamimab, an investigational light chain–depleter antibody studied with antiplasma cell dyscrasia therapy for newly diagnosed patients in the CARES trial (NCT04512235 and NCT04504825). In July 2025, that trial failed to meet its end point for Mayo phase 3a and 3b AL amyloidosis; however, results presented Friday show the treatment does offer benefits for patients newly diagnosed within a subgroup, κ light chain amyloidosis.² Although the phase 1 portion of LINKER-AL2 centers on safety and dose escalation, the strong hematologic responses drew reactions. Lee noted both the high CR rates and how quickly they occurred when The American Journal of Managed Care^® (AJMC^®) asked for his reaction.

“The hematologic [CR] rate of 90%, which was attained at a median time of 1.5 months, is unprecedented in this patient population,” Lee said in an email. “To contextualize these results, there are no approved treatment options for relapsed/refractory AL amyloidosis, and small prospective studies have reported hematological CR rates of [less than] 50% using conventional regimens adapted from multiple myeloma treatment.

“Moreover, the hematologic [CR] rates with Dara-VCd, which is the only approved treatment for newly diagnosed AL amyloidosis, demonstrated a hematologic [CR] of 53% at a similar median follow-up of what is reported in the phase 1 part of the LINKER-AL 2 study.”

During his presentation, Lee highlighted that the reduction in involved free light chain levels took place at both doses in just 15 days; this is crucial to halting the disease process that causes organ injury and, depending on the depth of the response and extent of the injury, can allow organs to heal.

Goal of Phase 1 Is Evaluating Safety

The goal of the phase 1 dose-escalation phase is to evaluate the safety and tolerability of linvoseltamab in these patients, who received doses of either 80 mg or 240 mg, and determine the recommended phase 2 dose. Phase 1 has a primary end point of dose-limiting toxicities through day 28.

A step-up schedule called for giving patients 5 mg of linvoseltamab intravenously on week 1, day 1 and 25 mg on week 2, day 8. Then, patients receive the full dose via subcutaneous injection once weekly for cycles 1 to 2 and once every 4 weeks for cycles 3 to 12; patients could have a maximum of 24 cycles.

Results for the first 20 patients were as follows:

• Median patient age was 64 years; 45% of the patients had cardiac involvement and 40% had renal involvement. Eight patients were Mayo stage II and 7 were Mayo stage IIIA.
• At the data cutoff, 7 patients had received the 80-mg dose and 13 received the 240-mg dose. Median follow-up was 12.1 weeks for the 80-mg dose and 6.7 weeks for the 240-mg dose.
• At the 80-mg dose, 2 patients had a grade 1 cytokine release syndrome (CRS) event, and 2 had a grade 2 CRS event. At the 240-mg dose, 5 patients had a grade 1 CRS event and 1 had a grade 2 event. No patient at either dose had a CRS event of grade 3 or higher.
• Median time to the first CRS event in hours was 28.2 for the 80-mg dose and 15.4 for the 240-mg dose. The median duration was 10.8 hours for the 80-mg dose and 13.8 for the second dose.
• At the 80-mg dose, 5 patients had infections, including 1 of grade 3/4. At the 240-mg dose, 12 patients had infections, including 4 grade 3/4.
• 1 patient developed immune effector cell–associated neurotoxicity syndrome, which resolved to allow the patient to continue on linvoseltamab. No dose-limiting toxicities occurred.
• Lee explained that 2 patients experienced treatment-emergent adverse events that led to death. One patient with preexisting coronary artery disease had an event while having a stent placement; the other, having achieved hematologic CR, also had a history of cardiac amyloidosis and experienced sudden death. Both events were deemed not related to linvoseltamab.

Ease of Administration for Physicians, Patients

Besides the early signs of strong responses combined with a favorable safety profile, linvoseltamab could be a very accessible treatment for patients with AL amyloidosis.

In response to questions from AJMC, Lee noted that all CRS incidents were grade 1 or 2 and “very manageable.” He explained that patients with AL amyloidosis are “generally frailer given their organ involvement of disease,” and close monitoring is required in the step-up phase. Nonetheless, Lee said the strategies that are allowing outpatient treatment for patients with bispecific antibodies for other diseases, including multiple myeloma, “could be employed” to allow full outpatient treatment for patients with AL amyloidosis.

“Linvoseltamab [intravenous] administration of the step-up dosing was employed for the LINKER-AL2 study based on available data of linvoseltamab in previous studies in multiple myeloma,” Lee said. “However, subcutaneous step-up dosing is being studied in other clinical trials of linvoseltamab and may be studied in patients with AL amyloidosis in the future.”

For patients, he said, “What makes linvoseltamab as a bispecific T-cell antibody particularly attractive is the fact that it is an off-the-shelf T-cell–redirecting therapy, which will allow broader access to patients in need of this therapy in their local treatment setting with a manageable safety profile.”

References

1. Wechalekar AD, Lee HC, Palladini G, et al. First results from the phase 1/2 LINKER-AL2 trial of linvoseltamab (LINVO) in patients (pts) with relapsed or refractory (RR) systemic light chain (AL) amyloidosis. J Clin Oncol. 2026;44(suppl 16):7502. doi:10.1200/JCO.2026.44.16_suppl.7502

2. Wechalekar AD, Dispenzieri A, Sachorawala V, et al. Phase 3 randomized trial to evaluate the impact of anselamimab on all-cause mortality in κ light-chain amyloidosis. J Clin Oncol. 2026;44(suppl 16):7501. doi:10.1200/JCO.2026.44.16_suppl.7501