Response to Daratumumab for Relapsed/Refractory Light Chain Amyloidosis in a Real-World Setting

Daratumumab (Darzalex) is a monoclonal antibody that blocks the plasma cell surface protein CD38. Daratumumab has recently been approved by the FDA for the treatment of light chain (AL) amyloidosis. The real-world effectiveness of daratumumab in patients with AL amyloidosis who have not responded to other therapies is unclear because there are few studies published to date with this patient population.

A recent retrospective cohort study was designed to address this gap. A total of 30 patients received daratumumab with a median follow-up of 24.3 months. Equal numbers of patients received daratumumab as either a second- or third-line therapy or as a fourth-line or higher therapy. Eleven patients received daratumumab as a monotherapy.

Based on the difference between involved and uninvolved free AL levels, the hematologic overall response rate was 93.3%, with 80% of patients meeting the threshold for a very good response rate. Fourteen of 30 patients had a complete response. The median time to response was <2 months. Five patients discontinued daratumumab for complete response or completion of treatment.

The median time of progression-free survival was estimated to be 28 months. There was no difference in progression-free survival between responders with low-involved free AL levels versus high-involved free AL levels.

A total of 21 patients had cardiac involvement, 1 of whom had achieved cardiac response with previous therapy. Of the 20 patients who could be evaluated for a response to daratumumab, 11 had a cardiac response. The median time to cardiac response was 7 months.

Seventeen patients had renal involvement, 2 of whom responded to previous therapy and 3 of whom were receiving dialysis. The renal response rate was lower than the cardiac response rate with 4 patients responding to daratumumab, none of whom had been receiving dialysis.

Daratumumab was well-tolerated in most patients. Adverse events included infusion-related reactions during the first treatment in 20% of patients, pneumonia, upper respiratory tract infections leading to discontinuation in 1 patient, and death from infection in 1 patient. The researchers speculated that daratumumab could have contributed to the death.

Limitations of the study included the small sample size and limited follow-up, the use of retrospective analysis from only 1 institution, and varying lengths of time for response assessments.

The researchers concluded that their results support the use of daratumumab in patients with AL amyloidosis that has not responded to previous therapies. Because of the small sample size and retrospective study design, they stated that the results will need to be verified in large prospective studies.

Source: Dima D, Hu X, Dower J, et al. Pattern of use and efficacy of daratumumab-based therapy in patients with relapsed/refractory light chain amyloidosis in a real-world setting: a single institution experience. Leuk Lymphoma. 2022;1-5.

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