Efficacy and Safety of Daratumumab in Light Chain Amyloidosis: A Single-Center Retrospective Study

Purpose

Light chain amyloidosis (AL) is a disease marked by the misfolding of immunoglobulin light chains, leading to amyloid deposits in various tissues and organs. The prognosis is particularly poor for patients with significant organ involvement. Daratumumab, an anti-CD38 monoclonal antibody, has shown promising results with an overall response rate (ORR) exceeding 80% in various studies. This retrospective study aims to evaluate the efficacy and safety of Daratumumab in treating AL amyloidosis, providing additional clinical insights.

Methods

The study included newly diagnosed or relapsed/refractory AL patients treated at Tongji Hospital, Huazhong University of Science and Technology, between May 2021 and May 2024. Patients received at least three courses of Daratumumab, administered in various regimens: Daratumumab with lenalidomide and dexamethasone (DRD group), bortezomib and dexamethasone (DVD group), pomalidomide and dexamethasone (DPD group), selinexol and dexamethasone (SDD group), isazomib and dexamethasone (DID group), dexamethasone alone (DD group), and carfizomib and dexamethasone (DKD group). Efficacy was measured through hematological remission and organ response.

Results

The study cohort consisted of 41 patients, with 31 initially diagnosed and 10 relapsed/refractory. The median age was 59 years (range: 38-75). Of these patients, 56.1% were classified as Mayo stage III-IV, with 76% having cardiac involvement, 52% with renal involvement, and 13 with dual cardiac and renal involvement. Median NT-proBNP was 2375 ng/L, median 24-hour urine protein was 0.683 g, median estimated glomerular filtration rate (eGFR) was 71.1 mL/min/1.73 m², and median difference free light chain (dFLC) was 132.05 mg/L. The DRD group showed 72.2% achieving very good partial response (VGPR) or better at 12 months, while 60% in the DVD group reached similar outcomes. Overall, the ORR at one month was 53.6% (22/41), including 4 complete remissions (CR), 14 VGPR, and 4 partial remissions (PR). At six months, the ORR increased to 72.9% (27/37), with 10 CRs, 13 VGPRs, and 4 PRs, reaching 90.9% (10/11) at 12 months, comprising 8 CR, 1 VGPR, and 1 PR. Cardiac response rates improved from 48.3% at three months to 78% at six months and 85% at 12 months. Among those with renal involvement, 52.3% demonstrated an organ response at 12 months. These findings indicate that Daratumumab not only significantly improves hematological outcomes but also promotes recovery of organ function.

Conclusion

This retrospective study confirms that Daratumumab is an effective and safe treatment option for AL amyloidosis, delivering rapid and sustained hematologic and organ responses. Most adverse events were mild and manageable, affirming the treatment's safety profile. However, the retrospective design and small sample size may limit the study's applicability. Larger, randomized controlled trials are necessary to validate these findings and further optimize the use of Daratumumab in clinical practice for AL amyloidosis.

No relevant conflicts of interest to declare.