Daratumumab is effective in the relapsed or refractory systemic light‐chain amyloidosis but associated with high infection burden in a frail real‐life population

Daratumumab for relapsed AL amyloidosis—When cumulative real‐world data precedes clinical trials: A multisite study and systematic literature review

“…We present outcomes of a multisite cohort of RRAL patients treated with DARA in a real‐world setting, confirming favorable safety and efficacy. These results are in line with other recent reports by several groups 14‐23 . By comparison, most of the patients in our cohort received DARA in combination with IMiDs as second‐line therapy, thus earlier in their course of treatment.…”

“…These results are in line with other recent reports by several groups. [14][15][16][17][18][19][20][21][22][23] By comparison, most of the patients in our cohort received DARA in combination with IMiDs as second-line therapy, thus earlier in their course of treatment.…”

“…A systematic review of the literature on DARA for RRAL according to prespecified criteria identified 57 publications between October 2016 and April 2020. Of these, 45 were excluded (14 not specific to amyloidosis, 9 case reports, 8 reviews, 7 studies describing patients later included in a larger cohort, 3 papers not describing RRAL, and 4 studies not reporting efficacy outcomes) and 12 studies met above‐mentioned eligibility (Tables 3‐5), describing 10 case series 14‐23 and 2 phase 2 studies 11,12 . Data included a total of 579 patients (including our own), 517 in case series and 62 in clinical trials; 394 patients received DARA as monotherapy and 185 in combinations with other agents (mostly bortezomib).…”

“…This approach was adopted by several centers around the world, leading to accumulation of further data, comprising mostly of case series as well as 2 prospective trials in RRAL with modest sample sizes. 11,12 DARA was shown to have high activity in AL amyloidosis both in newly diagnosed 13 and in relapsed [14][15][16][17][18][19][20][21][22][23] patients.…”

Roles of CD38 in the Immune Response to Infection

“…Infections reported as drug-related adverse effects include opportunistic bacterial infections of the respiratory or urinary tracts (e.g., S. pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus, Escherichia coli and Haemophilus influenzae), exogenous viral infections (e.g., acute respiratory syncytial virus, human metapneumovirus and influenza A and B viruses) and viral reactivations (e.g., cytomegalovirus, herpes simplex virus and varicella-zoster virus). Furthermore, increased risk of infection was also observed in a study exploring the effects of daratumumab in patients with systemic light-chain amyloidosis [94] and in clinical trials using isatuximab, a separate anti-CD38 monoclonal antibody, for multiple myeloma [95,96]. Of note, many patients undergoing anti-CD38-based immunotherapy are in relapsed or refractory phases of the disease and have been heavily treated, which implies that immunosuppression derived from previous lines of treatment could influence the risk of infection.…”