Hans Lee, MD, Discusses “Off-the-Shelf” Solution for Rare Blood Disorder With No Approved Therapies

Finding a new use for an approved therapy is always welcome news. Finding a use that improves outcomes for a condition where there are no approved therapies offers hope—and that’s what happened on May 29, 2026, when Hans Lee, MD, presented data for the first 20 patients enrolled in LINKER-AL2 (NCT06292780). This early-stage study is evaluating linvoseltamab (Lynozyfic; Regeneron) in patients with systemic light chain (AL) amyloidosis, a life-threatening condition that causes organ damage and has no approved treatments once patients relapse. Lee presented findings from the phase 1 dose-escalation portion of the study at the American Society of Clinical Oncology Annual Meeting. The study is evaluating responses to 80-mg and 240-mg doses.¹

In response to a request from The American Journal of Managed Care (AJMC), Lee offered written responses to questions about these new data and what will come next.

AJMC: Several therapies, including venetoclax and chimeric antigen receptor (CAR) T-cell therapy, are being evaluated for the treatment of AL amyloidosis. What sets linvoseltamab apart from other strategies for treating this rare disease?

Lee: Early data from T-cell–redirecting therapies with bispecific antibodies and CAR T have shown unprecedented depth and speed of hematologic responses compared to conventional non–T-cell–redirecting therapies. In the phase 1 part of the LINKER-AL2 study, the hematologic complete response rate was 90% with a median onset of 1.5 months among 20 [patients with relapsed/refractory AL amyloidosis] enrolled on study. 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.

AJMC: Your study tested linvoseltamab at 80 mg and 240 mg, with no dose-limiting toxicities or [immune effector cell–associated neurotoxicity syndrome] at either dose. High overall response rates were seen, and the early abstract indicates responses were expected to deepen over time. At this point, does the study team have a recommended dose?

Lee: We are encouraged by the rapid and deep responses as well as the safety profile at both dose levels of linvoseltamab. The phase 2 part for the LINKER-AL2 study is currently ongoing, which is [randomly assigning] patients to the 80-mg or 240-mg doses of linvoseltamab, to further inform dose selection with potential registrational intent.

AJMC: How would you characterize the responses to linvoseltamab, especially relative to responses to other available options for this population?

Lee: The hematologic complete response rate of 90%, which was attained at a median time of 1.5 months, is unprecedented in this patient population. To contextualize these results, there are no approved treatment options for relapsed/refractory AL amyloidosis, and small prospective studies have reported hematological [complete response] rates of less than 50% using conventional regimens adapted from multiple myeloma treatment. Moreover, the hematologic complete response rates with Dara-VCd (daratumumab, cyclophosphamide, bortezomib, and dexamethasone), which is the only approved treatment for newly diagnosed AL amyloidosis, demonstrated a hematologic complete response of 53% at a similar median follow-up of what is reported in the phase 1 part of the LINKER-AL 2 study.¹

AJMC: Based on the low-grade cytokine release syndrome (CRS) reported, do you anticipate any challenges offering this treatment in an outpatient setting? Could the intravenous step-up doses ever be shifted to subcutaneous in the future, as clinicians gain experience with this therapy with these patients?

Lee: CRS rates observed with linvoseltamab were mostly grade 1, some grade 2, and no grade 3 or higher CRS events, and [were] very manageable. [Patients with AL amyloidosis] are generally frailer, given their organ involvement of disease, so they do need to be monitored closely during the step-up dosing period. With that said, bispecific T-cell antibody step-up dosing in general is shifting more to the outpatient setting as CRS mitigation strategies are adopted—such as prophylactic tocilizumab—and such strategies could be employed in the future with linvoseltamab. 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. 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.

Reference

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