ABSTRACT Introduction/Aims Eplontersen is approved in multiple regions for adults with hereditary transthyretin amyloidosis with polyneuropathy (ATTRv‐PN). This exploratory analysis was conducted to evaluate the treatment effect of eplontersen by sex in patients with ATTRv‐PN from the NEURO‐TTRansform trial (NCT04136184). Methods Participants in NEURO‐TTRansform who received ≥ 1 dose of eplontersen were included in this analysis; participants in the inotersen reference group who switched to eplontersen were excluded. Eplontersen was evaluated in the overall patient population and in a subgroup with cardiomyopathy. Change from baseline in the NEURO‐TTRansform primary endpoints of serum transthyretin (TTR) levels to Week 65, modified Neuropathy Impairment Score +7 (mNIS+7) composite score to Week 66, and Norfolk Quality of Life‐Diabetic Neuropathy (Norfolk QoL‐DN) total score to Week 66 were evaluated. A historical placebo group from the NEURO‐TTR trial (NCT01737398) was included as a control. Results The eplontersen group comprised 100 (69.4%) male and 44 (30.6%) female patients. The placebo group comprised 41 (68.3%) male and 19 (31.7%) female patients. For both sexes, treatment with eplontersen decreased serum TTR levels by > 80% (vs. reductions of 3%–13% with placebo), maintained mNIS+7 scores, and improved Norfolk QoL‐DN scores (vs. deterioration with placebo). The treatment effect of eplontersen was similar in male and female patients with cardiomyopathy. Discussion Eplontersen halted neuropathy impairment and improved quality of life versus placebo to a similar degree in both male and female patients with ATTRv‐PN, including those with cardiomyopathy. These findings support the use of eplontersen as an effective treatment for ATTRv‐PN regardless of sex.
American Society of Hematology 2026 guidelines on diagnosis of light chain amyloidosis
Background Light chain (AL) amyloidosis is a rare disease caused by the misfolding of immunoglobulin light chains produced by a plasma cell dyscrasia. Patients can present with involvement of many organs, including the heart, kidneys, liver, nerves, and other sites, resulting in a high symptom burden. Timely and accurate diagnosis is important to prevent organ failure and improve patient survival. Objective These evidence-based guidelines of the American Society of Hematology (ASH) are intended to support patients and clinicians in the timely and effective diagnosis of AL amyloidosis. Methods ASH formed a multidisciplinary guideline panel that included 22 individuals representing various medical specialties (academic and community hematology, nephrology, neurology, cardiology, internal medicine, and pathology) as well as 1 patient representative. The group was balanced to minimize potential bias from conflicts of interest. The University of Kansas Medical Center supported the guideline development process, including updating or performing systematic evidence reviews (up to 6 March 2023). The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients. The panel used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, including GRADE evidence-to-decision frameworks, to assess evidence and make recommendations, which were subject to public comment. Results The panel agreed on 12 recommendations. Conclusions The use of serum immunofixation, urine immunofixation, and serum free light chains enhances the clinical suspicion of AL amyloidosis. The diagnosis of AL amyloidosis can be made effectively through surrogate biopsies, which require both a bone marrow biopsy and fat-pad sampling; however, target organ biopsies may be favored in certain clinical situations.