Efficacy and safety of intravenous daratumumab-based treatments for AL amyloidosis: a systematic review and meta-analysis

Abstract

Background Intravenous daratumumab (DARA IV) has been increasingly used in the treatment of amyloid light-chain (AL) amyloidosis. However, the outcomes for patients administered with DARA IV have not been aggregated. The objective of this systematic review and meta-analysis was to investigate the efficacy and safety of DARA IV for AL amyloidosis. Methods We searched Medline, EMBASE, Cochrane Library and Web of Science up to 17 June 2021. Response rates and survival rates, and the corresponding 95% confidence intervals (CIs) were pooled and calculated using a fixed-effects model. Results Thirty studies (5 cohort studies and 25 single-arm studies) with 997 patients were included. In patients receiving DARA IV-based treatments, very good partial response or better response rate, complete response rate, very good partial response rate, partial response rate and overall response rate were 66% (95% CI, 62–69%), 30% (95% CI, 23–36%), 40% (95% CI, 33–46%), 17% (95% CI, 14–21%), and 77% (95% CI, 73–80%), respectively. Cardiac and renal responses were 41% (95% CI, 34–49%) and 43% (95% CI, 32–54%), respectively. 58% (95% CI, 49–66%) of patients achieved PFS one year or longer. 2.5% (range, 1–10.0%) of patients experienced grade 3 or 4 adverse events, of which the most common adverse event was lymphocytopenia (range, 13.6–25.0%). Conclusion This study supports the efficacy and safety of DARA IV for the treatment of patients with AL amyloidosis.

Cardiac Amyloidosis

“…There are several different choices of anti-plasma cell medications (alkylating agents, immunomodulatory drugs (IMiDs) and proteosomes inhibitors) approved for treatment of myeloma multiple and can be used off-label for the treatment of AL amyloidosis. Daratumumab is the first monoclonal Ab that has been demonstrated to be highly effective in the treatment of AL-CA [70]. The intensity and type of therapy chosen is affected by the number and extent of organ involvement.…”

Cardiovascular toxicity from therapies for light chain amyloidosis

“…The most common CV adverse events in the daratumumab group included cardiac failure (9.3% vs. 7.4%), syncope (5.2% vs. 6.4%), peripheral edema (3.1% vs. 5.9%), and hypokalemia (1.6% vs. 5.3%) ( 125 ). A recent metanalysis found that the most common severe AEs in AL amyloidosis are lymphocytopenia, HF (4%–13%), infection complications, pneumonia, fatigue (0%–9%), atrial fibrillation (0%–18%), neutropenia, and diarrhea ( 126 ).…”