Daratumumab Monotherapy Shows Promise for Severe AL Amyloidosis with Renal Involvement

Monotherapy with daratumumab, an anti-CD38 human monoclonal IgG1κ antibody, showed clinical efficacy in treating patients with severe immunoglobulin light chain (AL) amyloidosis and biopsy-proven renal involvement, according to findings from a small study published in the Journal of Clinical Medicine.

AL amyloidosis, when the immune system produces abnormal antibodies called light chains, is associated with short survival. The therapy goal for this disorder is suppression pathologic light chain precursor production in order to improve organ impairment. Current treatments, such as daratumumab, have been adopted from multiple myeloma and are based on chemotherapy that targets the underlying plasma cell clone.

This trial aimed to assess clinical activity and toxicity of daratumumab as a single agent in the treatment of AL amyloidosis. Five patients with severe AL amyloidosis and biopsy-proven renal involvement received daratumumab 16 mg/kg intravenously weekly for eight consecutive weeks, then every two weeks for eight cycles, and finally once monthly for up to 52 weeks. Two patients were either refractory or intolerant to conventional bortezomib-based therapy, two were treated for relapsing disease, and one was receiving daratumumab as frontline therapy.

Daratumumab demonstrated clinical efficacy, with a reduction in M-proteins in four out of five patients, serum free light chains (sFLC) ratio normalization in three out of four, and amelioration in the remaining patient. The four patients with preserved renal function at baseline also showed serum creatinine stabilization and a decrease in proteinuria.

“Our data, based on real-life experience and strong parameters of definition of the renal involvement, showed this regimen to be a beneficial therapeutic option capable not only of inducing rapid hematologic response but also achieving a substantial rate of renal improvement in pretreated and naïve patients,” the researchers concluded.