Daratumumab Shows Efficacy in Previously Treated Systemic Light-Chain Amyloidosis

Daratumumab, an anti-CD38 monoclonal antibody indicated for the treatment of patients with multiple myeloma (MM), has also shown efficacy in patients with systemic light-chain (AL) amyloidosis, according to results from a phase II study presented at the 2017 ASH Annual Meeting.

“Plasma cells in AL amyloidosis are similar to plasma cells in MM and always express CD38,” explained lead author Murielle Roussel, MD, of the Hematology Department, IUCT-Oncopole in Toulouse, France, and co-authors. In this multicenter, prospective trial, the researchers evaluated whether daratumumab could be an option for patients with previously treated AL amyloidosis.

Forty people were included in this study (median age = 69 years; range = 45-81 years). All had previously treated measurable AL amyloidosis that had not responded to therapy, as well as at least one major vital organ involvement, an Eastern Cooperative Oncology Group performance status score of ≤2, and measurable plasma cell dyscrasia with difference between involved and uninvolved free AL levels (dFLC) >50 mg/L.

Patients had received a median of 2.5 prior therapies (range = 1-5 therapies), including melphalan and dexamethasone (n=13), bortezomib (n=28), and lenalidomide (n=14).

Intravenous daratumumab 16 mg/kg was administered once-weekly during the first two 28-day cycles, then every other week during cycles three through six, for a total of six 28-day cycles.

Four patients discontinued the study treatment before six cycles because of disease progression (n=2), death (n=1), or lung cancer (n=1).

Hematologic responses were measured after each injection and at the end of each cycle. As of July 31, 2017 (data cutoff), patients had been followed for a median of 23 months (range = 3.5-116 months).

Thirty-two patients completed at least one cycle of daratumumab treatment (at least 4 injections) and were evaluable for response. At six months after treatment initiation, or at last evaluation, 19 patients responded to daratumumab, for an overall response rate of 59.4 percent. This included 14 very good partial responses or better (≥VGPR; 43.8%) and five partial responses (PR; 15.6%); the remaining 13 patients (40.6%) did not respond.

After a single daratumumab injection, all 19 responding patients had a greater than 30-percent reduction in dFLC from baseline, with a median dFLC decrease after one injection of 57 percent (range = 31-96%).

“The administration of daratumumab was associated with a good safety profile and non-severe adverse events (AEs), mostly after the first infusion,” the authors reported. Six patients experienced at least one grade ≥3 AE, and only one event (lymphopenia) was considered related to daratumumab. The most common drug-related AEs were infusion-related reaction in 10 patients, all of which were grade 1 or 2.

“Daratumumab demonstrates encouraging efficacy in previously treated patients with AL amyloidosis with deep and rapid responses,” the authors concluded. They noted that these results warrant larger and longer-term studies of daratumumab in this setting.

The study’s findings are limited by the small number of patients enrolled and the lack of a comparator arm.

The authors report relationships with Janssen, the manufacturer of daratumumab.


Roussel M, Stoppa A, Perrot A, et al. A prospective phase II of daratumumab in previously-treated systemic light-chain (AL) amyloidosis. Abstract #508. Presented at the 2017 American Society of Hematology Annual Meeting, December 10, 2017; Atlanta, GA.