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.

Case series: MRD negativity assessment using 11C-Acetate PET with 3-weekly daratumumab-based quadruplet induction in newly diagnosed multiple myeloma

“…The Dara-based regimen used was a 3-weekly regimen. 14,15 Daratumumab was given as an infusion at a dose of 16 mg/kg once every three weeks. Bortezomib was given at a dose of 1.3 mg/m 2 once a week.…”

“…In view of the long plasma half-life of daratumumab, 12 as well as the success of 3-weekly rituximab in the rituximab, cyclophosphamide, hydroxydaunomycin, vincristine (R-CHOP) regimen for lymphoma, 13 a 3-weekly daratumumab-based induction regimen has been proposed and adopted in our center. 14,15 Herein, we report three newly diagnosed MM patients achieving imaging CR with ACT PET, in addition to conventional immunofixation CR and MRD-negative CR after a 3-weekly daratumumabbased induction regimen. 2…”