MEETING NEWS LYMPHOMA
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 .
REFERENCE
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 .
SCENES FROM THE 2017 ASH ANNUAL MEETING
14 Focus on Lymphoma & Myeloma