Daratumumab monotherapy elicited deep and rapid hematological responses in previously treated AL patients, with a good safety profile
Patients in VGPR or better can experience long lasting responses after 6 months of daratumumab monotherapy
Daratumumab is a human monoclonal antibody targeting CD38, an antigen uniformly expressed by plasma cells in multiple myeloma and light chain amyloidosis (AL). We report the results of a prospective multi-center, phase 2 study of daratumumab monotherapy in AL (NCT02816476). Forty previously treated AL patients with a difference between involved and uninvolved free light chains (dFLC) > 50 mg/L were included in 15 centers between 9/2016 and 4/2018. Patients received six 28-day cycles of IV daratumumab, QW for cycles 1-2 and Q2W for cycles 3-6. Median age was 69 years (range 45-83). Twenty-six patients had 2 or more organs involved with heart in 24 and renal in 26. Median time from diagnosis to enrollment was 23 months (IQR: 4-122) with a median of 3 prior therapies (range 1-5). At data cut-off (09/2019), all patients discontinued therapy and 33 received the planned 6 cycles. Overall, 22 patients had hematological response and 19 patients (47.5%) achieved Very Good Partial Response (dFLC<40mg/l) or better. Median time to hematological response was 1 week. Patients with no response after 4 doses were unlikely to further respond. Renal and cardiac responses occurred in 8 and 7 patients, respectively. Daratumumab was well tolerated with no unexpected adverse events. With a median follow-up of 26 months, the 2-year overall survival rate was 74% (95% CI: 62-81). Daratumumab monotherapy is associated with deep and rapid hematological responses in previously treated AL patients, with a good safety profile. Further studies of daratumumab in combination regimens are warranted.