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Abstract
Abstract: LB2238

Type: Presidential Symposium

Presentation during EHA21: On Friday, June 10, 2016 from 16:47 - 17:00

Location: Hall A1

Background
Daratumumab (D), a human anti-CD38 IgGκ monoclonal antibody, was associated with rapid, deep, and durable responses and a favorable safety profile when combined with lenalidomide and dexamethasone (Rd) in a phase 1/2 study of relapsed or relapsed and refractory multiple myeloma pts (Plesner T, et al. ASH 2015, Abs. 507).
Aims: To compare the efficacy and safety of D in combination with Rd vs Rd alone in pts with RRMM in a randomised, open-label, multicenter, phase 3 study (POLLUX; NCT02076009).

Aims
To compare the efficacy and safety of D in combination with Rd vs Rd alone in pts with RRMM in a randomised, open-label, multicenter, phase 3 study (POLLUX; NCT02076009).

Methods
Pts who received at least 1 prior line of therapy for myeloma were randomised (1:1) to R 25 mg orally on Days 1-21 of each 28-day cycle and d 40 mg weekly, with or without D (16 mg/kg qw for 8 weeks, q2w for 16 weeks, then q4w until progression). The primary endpoint is progression-free survival (PFS). Secondary endpoints are time to progression (TTP), overall response rate (ORR), rate of very good partial response (VGPR) or better, minimal residual disease–negative rate, overall survival (OS), duration of response, time to response, and safety.

Results
569 pts were randomised. Median age of pts was 65 years old. Pts received a median of 1 prior line of therapy (range 1-11), with 19% of pts with ≥3 prior lines of therapy. Eighty-six percent received a prior PI, and 55% received prior IMiD, including 18% prior R, with 44% having received both a PI and an IMiD; 27% were refractory to the last line of prior therapy, 18% were PI refractory, and none were R refractory. After a median follow-up of 13.5 months, D significantly improved median PFS (63% reduction in the risk of progression/death) for DRd vs Rd (Figure). Addition of D to Rd significantly delayed TTP vs Rd (not reached [NR] vs estimated median of 18.4 mo; hazard ratio, 0.34; 95% CI, 0.23-0.48; P<0.0001). D significantly increased ORR (93% vs 76%, P<0.0001) and rates of VGPR or better (76% vs 44%, P<0.0001) and complete response (CR) or better (43% vs 19%, P<0.0001) for DRd vs Rd, respectively. The median duration of response was NR for DRd vs 17.4 months for Rd. All preplanned sensitivity analyses were consistent with results from the primary analysis. Pre-specified subgroup analyses of PFS demonstrated that the treatment effect of DRd over Rd was consistent across all pre-specified subgroups. The most common (<25%) TEAEs (DRd/Rd) were neutropenia (59%/43%), diarrhea (43%/25%), fatigue (35%28%), upper respiratory tract infection (32%/21%), anemia (31%/35%), constipation (29%/25%), cough (29%/13%), thrombocytopenia (27%/27%), and muscle spasms (26%/19%). Most common grade 3/4 TEAEs (>10%) were neutropenia (52%/37%), thrombocytopenia (13%/14%), and anemia (12%/20%). The rate of Grade 3/4 infections/infestations was 28% in the DRd group and 23% in the Rd group and the most common Grade 3/4 infections/infestations TEAE (≥5%) was pneumonia (8%/8%). Similar rates of treatment discontinuation due to TEAEs were observed (7%/8%). D-associated infusion-related reactions (IRR; 48% of pts) mostly were grade 1/2 (grade 3/4, 5%/0%); most (92% of IRRs) occurred during the first infusion.

Summary/Conclusion
DRd was superior to Rd alone. A significant reduction in the risk of disease progression/death was demonstrated with DRd vs Rd. DRd induced deep and durable responses, including doubling stringent CR/CR rates and significantly increasing the rate of VGPR or better vs Rd alone. DRd was associated with a manageable safety profile consistent with the known safety profile of D and Rd. The combination of D and Rd potentially represents a new standard of care for pts with >1 prior treatment.



Session topic: Presidential Symposium

Keyword(s): Multiple myeloma
Abstract: LB2238

Type: Presidential Symposium

Presentation during EHA21: On Friday, June 10, 2016 from 16:47 - 17:00

Location: Hall A1

Background
Daratumumab (D), a human anti-CD38 IgGκ monoclonal antibody, was associated with rapid, deep, and durable responses and a favorable safety profile when combined with lenalidomide and dexamethasone (Rd) in a phase 1/2 study of relapsed or relapsed and refractory multiple myeloma pts (Plesner T, et al. ASH 2015, Abs. 507).
Aims: To compare the efficacy and safety of D in combination with Rd vs Rd alone in pts with RRMM in a randomised, open-label, multicenter, phase 3 study (POLLUX; NCT02076009).

Aims
To compare the efficacy and safety of D in combination with Rd vs Rd alone in pts with RRMM in a randomised, open-label, multicenter, phase 3 study (POLLUX; NCT02076009).

Methods
Pts who received at least 1 prior line of therapy for myeloma were randomised (1:1) to R 25 mg orally on Days 1-21 of each 28-day cycle and d 40 mg weekly, with or without D (16 mg/kg qw for 8 weeks, q2w for 16 weeks, then q4w until progression). The primary endpoint is progression-free survival (PFS). Secondary endpoints are time to progression (TTP), overall response rate (ORR), rate of very good partial response (VGPR) or better, minimal residual disease–negative rate, overall survival (OS), duration of response, time to response, and safety.

Results
569 pts were randomised. Median age of pts was 65 years old. Pts received a median of 1 prior line of therapy (range 1-11), with 19% of pts with ≥3 prior lines of therapy. Eighty-six percent received a prior PI, and 55% received prior IMiD, including 18% prior R, with 44% having received both a PI and an IMiD; 27% were refractory to the last line of prior therapy, 18% were PI refractory, and none were R refractory. After a median follow-up of 13.5 months, D significantly improved median PFS (63% reduction in the risk of progression/death) for DRd vs Rd (Figure). Addition of D to Rd significantly delayed TTP vs Rd (not reached [NR] vs estimated median of 18.4 mo; hazard ratio, 0.34; 95% CI, 0.23-0.48; P<0.0001). D significantly increased ORR (93% vs 76%, P<0.0001) and rates of VGPR or better (76% vs 44%, P<0.0001) and complete response (CR) or better (43% vs 19%, P<0.0001) for DRd vs Rd, respectively. The median duration of response was NR for DRd vs 17.4 months for Rd. All preplanned sensitivity analyses were consistent with results from the primary analysis. Pre-specified subgroup analyses of PFS demonstrated that the treatment effect of DRd over Rd was consistent across all pre-specified subgroups. The most common (<25%) TEAEs (DRd/Rd) were neutropenia (59%/43%), diarrhea (43%/25%), fatigue (35%28%), upper respiratory tract infection (32%/21%), anemia (31%/35%), constipation (29%/25%), cough (29%/13%), thrombocytopenia (27%/27%), and muscle spasms (26%/19%). Most common grade 3/4 TEAEs (>10%) were neutropenia (52%/37%), thrombocytopenia (13%/14%), and anemia (12%/20%). The rate of Grade 3/4 infections/infestations was 28% in the DRd group and 23% in the Rd group and the most common Grade 3/4 infections/infestations TEAE (≥5%) was pneumonia (8%/8%). Similar rates of treatment discontinuation due to TEAEs were observed (7%/8%). D-associated infusion-related reactions (IRR; 48% of pts) mostly were grade 1/2 (grade 3/4, 5%/0%); most (92% of IRRs) occurred during the first infusion.

Summary/Conclusion
DRd was superior to Rd alone. A significant reduction in the risk of disease progression/death was demonstrated with DRd vs Rd. DRd induced deep and durable responses, including doubling stringent CR/CR rates and significantly increasing the rate of VGPR or better vs Rd alone. DRd was associated with a manageable safety profile consistent with the known safety profile of D and Rd. The combination of D and Rd potentially represents a new standard of care for pts with >1 prior treatment.



Session topic: Presidential Symposium

Keyword(s): Multiple myeloma

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