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Abstract

Abstract: P334

Type: Poster Presentation

Presentation during EHA22: On Friday, June 23, 2017 from 17:15 - 18:45

Location: Poster area (Hall 7)

Background
Daratumumab, a human monoclonal antibody targeting CD38, significantly prolongs progression-free survival (PFS) and achieves deep and durable responses when combined with other established standard-of-care regimens in patients with RRMM.

Aims
To provide updated efficacy and safety data from POLLUX, a multicenter, phase 3, randomized study of DRd versus Rd in RRMM.

Methods
Eligible patients with 1 prior line of therapy were randomly assigned to Rd (25 mg PO lenalidomide on Days 1-21 of each every-4-week [Q4W] cycle; 40 mg dexamethasone weekly) with or without daratumumab (16 mg/kg IV once weekly for Cycles 1 and 2, every 2 weeks for Cycles 3-6, then Q4W until disease progression). Patients who were refractory to lenalidomide were excluded. Progression-free survival (PFS) was the primary endpoint. Bone marrow samples were collected, and minimal residual disease (MRD) was assessed at the time of suspected complete response (CR) and at 3 and 6 months after suspected CR at 3 different sensitivity thresholds (10–4, 10–5, and 10–6) using the ClonoSEQ™ next-generation sequencing-based assay (Adaptive Biotechnologies, Seattle, WA). Additional reflex testing using an anti-idiotype antibody was used to confirm CRs in cases in which daratumumab interference with serum M-protein quantitation was suspected in patients with possible CR. 

Results
Patients received a median (range) of 1 (1-11) prior lines of therapy; 55% of patients had received immunomodulatory agents (IMIDs), and 18% had been exposed to lenalidomide. After median follow-up of 17.3 months, DRd significantly prolonged PFS compared with Rd alone (median: not reached vs 17.5 months; hazard ratio [HR], 0.37; 95% confidence interval [CI], 0.28-0.50; P<0.0001), with 18-month PFS rates of 76% and 49%, respectively. Responses continued to deepen in the DRd group with longer follow-up, with significantly higher overall response rate (ORR; 93% vs 76%) and rates of very good partial response (VGPR) or better (78% vs 45%) and CR or better (46% vs 20%) with DRd versus Rd alone (P<0.0001 for all). MRD-negative rates were >3 times higher with DRd compared with Rd alone at all 3 sensitivity thresholds (31.8% vs 8.8% at 10–4; 24.8% vs 5.7% at 10–5; and 11.9% vs 2.5%, at 10–6; P<0.0001 for all), and MRD negativity was associated with prolonged PFS at 10–5 (Figure). Overall survival (OS) data are immature, with 40 (14%) deaths in the DRd group and 56 (20%) deaths in the Rd group (HR, 0.63; 95% CI, 0.42-0.95). Neutropenia was the most common grade 3 or 4 treatment-emergent adverse event (53% with DRd vs 38% with Rd), and no new safety signals were reported with longer follow up. We will present updated efficacy and safety data based on approximately 25 months follow up at the meeting.

Conclusion
DRd significantly improved outcomes compared with Rd alone, including PFS, ORR, depth of response, and MRD-negative rates, with a favorable safety profile that was maintained after longer follow up. These updated data continue to support the use of DRd in patients with RRMM who received 1 prior therapy.

Session topic: 14. Myeloma and other monoclonal gammopathies - Clinical

Keyword(s): Multiple Myeloma, Minimal residual disease (MRD), Immunotherapy, CD38

Abstract: P334

Type: Poster Presentation

Presentation during EHA22: On Friday, June 23, 2017 from 17:15 - 18:45

Location: Poster area (Hall 7)

Background
Daratumumab, a human monoclonal antibody targeting CD38, significantly prolongs progression-free survival (PFS) and achieves deep and durable responses when combined with other established standard-of-care regimens in patients with RRMM.

Aims
To provide updated efficacy and safety data from POLLUX, a multicenter, phase 3, randomized study of DRd versus Rd in RRMM.

Methods
Eligible patients with 1 prior line of therapy were randomly assigned to Rd (25 mg PO lenalidomide on Days 1-21 of each every-4-week [Q4W] cycle; 40 mg dexamethasone weekly) with or without daratumumab (16 mg/kg IV once weekly for Cycles 1 and 2, every 2 weeks for Cycles 3-6, then Q4W until disease progression). Patients who were refractory to lenalidomide were excluded. Progression-free survival (PFS) was the primary endpoint. Bone marrow samples were collected, and minimal residual disease (MRD) was assessed at the time of suspected complete response (CR) and at 3 and 6 months after suspected CR at 3 different sensitivity thresholds (10–4, 10–5, and 10–6) using the ClonoSEQ™ next-generation sequencing-based assay (Adaptive Biotechnologies, Seattle, WA). Additional reflex testing using an anti-idiotype antibody was used to confirm CRs in cases in which daratumumab interference with serum M-protein quantitation was suspected in patients with possible CR. 

Results
Patients received a median (range) of 1 (1-11) prior lines of therapy; 55% of patients had received immunomodulatory agents (IMIDs), and 18% had been exposed to lenalidomide. After median follow-up of 17.3 months, DRd significantly prolonged PFS compared with Rd alone (median: not reached vs 17.5 months; hazard ratio [HR], 0.37; 95% confidence interval [CI], 0.28-0.50; P<0.0001), with 18-month PFS rates of 76% and 49%, respectively. Responses continued to deepen in the DRd group with longer follow-up, with significantly higher overall response rate (ORR; 93% vs 76%) and rates of very good partial response (VGPR) or better (78% vs 45%) and CR or better (46% vs 20%) with DRd versus Rd alone (P<0.0001 for all). MRD-negative rates were >3 times higher with DRd compared with Rd alone at all 3 sensitivity thresholds (31.8% vs 8.8% at 10–4; 24.8% vs 5.7% at 10–5; and 11.9% vs 2.5%, at 10–6; P<0.0001 for all), and MRD negativity was associated with prolonged PFS at 10–5 (Figure). Overall survival (OS) data are immature, with 40 (14%) deaths in the DRd group and 56 (20%) deaths in the Rd group (HR, 0.63; 95% CI, 0.42-0.95). Neutropenia was the most common grade 3 or 4 treatment-emergent adverse event (53% with DRd vs 38% with Rd), and no new safety signals were reported with longer follow up. We will present updated efficacy and safety data based on approximately 25 months follow up at the meeting.

Conclusion
DRd significantly improved outcomes compared with Rd alone, including PFS, ORR, depth of response, and MRD-negative rates, with a favorable safety profile that was maintained after longer follow up. These updated data continue to support the use of DRd in patients with RRMM who received 1 prior therapy.

Session topic: 14. Myeloma and other monoclonal gammopathies - Clinical

Keyword(s): Multiple Myeloma, Minimal residual disease (MRD), Immunotherapy, CD38

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