3-weekly daratumumab-IMiD-dexamethasone is highly efficacious and cost-effective in relapsed/refractory multiple myeloma.

Abstract

e19521 Background: Daratumumab (dara) with immunomodulatory agents (IMiD) and dexamethasone (dex) is highly effective in relapsed multiple myeloma (MM). The recommended schedule of dara is weekly for 8 doses, followed by 2-weekly for 8 doses, and then every 4-weekly thereafter. Given the high cost and the long half-life as an antibody, a 3-weekly dosing of dara was used together with IMiD/dexamethasone. Methods: Dara at 16mg/kg was used every 3-weekly with lenalidomide or pomalidomide. Patient achieving best response received single agent IMiD maintenance until disease progression. Results: Fourteen relapsed MM patients were enrolled. One had received weekly dara from a private oncologist, hence was excluded from analysis. Thirteen patients at a median age of 63 years (range: 50-84 years) were studied. The median number of previous therapies was 2 (range: 1-5), with nine patients (69.2%) having undergone autologous stem cell transplantation. Three patients (23.1%) were refractory to bortezomib, seven patients (53.8%) to lenalidomide, and eight patients (61.5%) to last treatment. At relapse, two (15.4%) had high LDH, eight (61.5%) impaired renal function, and three (23.1%) extramedullary disease. Treatment was dara-lenalidomide-dex in six (46.2%), and dara-pomalidomide-dex in seven (53.8%). Responses after four cycles included CR in 5 patients (38.5%), VGPR in five patients (38.5%), and PR in three patients (23.1%). After a median of four dara infusions (range: 3-10), the best responses included CR in seven patients (53.8%), nCR in two patients (15.4%), VGPR in two patients (15.4%), and PR in two patients (15.4%). Median time to VGPR was one month. At 10 months, the OS was 90%, and PFS 54.7%. Three patients progressed, one of whom died of ruptured hepatic plasmacytoma. The most frequent toxicity was haematological especially neutropenia (all grades: 92.3%, Grade ¾: 76.9%), infusion reaction (38.5%, all grade ½), neuropathy (38.5%, all grade ½), gastrointestinal (all grades: 38.5%, grade ¾: 7.7%), and sepsis (all grades: 30.8%; grade ¾: 23.1%). Neutropenia was effectively prevented with prophylactic G-CSF. Conclusions: In conclusion , a 3-weekly dara-IMiD-dex regimen is highly efficacious, inducing deep and rapid responses, hence cost-effective for less affluent countries. In view of prevalent grade 3/4 neutropenia despite less frequent dara, 3-weekly dara might be more suitable for Asian patients.