According to research published in the British Journal of Haematology, daratumumab appears to be effective in relapsed or refractory systemic light-chain amyloidosis (AL); however, patients with AL are often frail, and the treatment was associated with various infections.
The retrospective analysis used data from all histologically proven patients with AL who were treated with daratumumab at 5 Hauts-de-France centers between November 2016 and March 2018. A total of 15 patients with a median age of 60 years had received 16 mg/kg intravenous daratumumab. A majority of patients (93%) had received 1 or more prior therapy (median, 2; range, 1-5).
At diagnosis, the median number of organs involved was 3 (range, 1-6), and 67% of patients had cardiac involvement. Patients had a median Eastern Cooperative Oncology Group Performance Status score of 2 (range, 0-3), a median cumulative Illness Rating scale score of 14 (range, 8-27), and a median Charlson Comorbidity index score of 4 (range, 1-8), suggesting that this patient population was frail.
All but 1 patient completed at least 1 cycle of daratumumab (median, 12 cycles). In patients who responded to treatment, best hematologic response was achieved after a median of 3 cycles (range 1-15). The overall response rate was 86%, with 43% of patients achieving complete response, 14% of patients achieving very good partial response, and 29% of patients achieving partial response.
Organ response was evaluated in 73% of patients. After a median of 4 cycles (range, 3-9), global organ response was observed in 45% of evaluable patients. After median follow-up of 7.9 months, 87% of patients were alive.
Infections were the most common adverse event (any grade, 60%; grade 3 or higher, 30%), including pneumonia (7 patients), upper respiratory tract infections (8 patients), and bacteremia (2 patients). There were 2 patient deaths, with 1 due to infection and the other due to disease progression.
“As a single agent, daratumumab allows deep fast hematologic responses in AL patients,” wrote the investigators. “Infectious complications were nonetheless noted, which should prompt close monitoring and rapid action.” They added that further research is necessary to determine the optimal treatment duration and explore the role of frailty scores in guiding infection prophylaxis.
Disclosures: Some authors have declared affiliations with the pharmaceutical industry. Please refer to the original study for a full list of disclosures.
1. Van de Wyngaert Z, Carpentier B, Pascal L, et al. Daratumumab is effective in the relapsed or refractory systemic light‐chain amyloidosis but associated with high infection burden in a frail real‐life population [published online November 19, 2019]. Br J Haematol. doi:10.1111/bjh.16282