Contributions
Abstract: EP1024
Type: E-Poster Presentation
Session title: Myeloma and other monoclonal gammopathies - Clinical
Background
Daratumumab (DARA), a human IgGκ monoclonal antibody that targets CD38, is approved for the treatment of NDMM in combination with standard-of-care regimens, including in combination with VMP based on results of the phase 3 ALCYONE trial. The phase 3 study OCTANS investigated the efficacy, safety, and pharmacokinetics (PK) of D-VMP in Asian NDMM patients.
Aims
To compare the efficacy, safety, and PK of D-VMP versus VMP in Asian and Chinese-only patients (NCT03217812).
Methods
Asian patients (from the following countries/regions: China, Hong Kong SAR, Taiwan, Korea, and Malaysia) with NDMM who were ineligible for autologous stem cell transplant were randomized (2:1) to D-VMP or VMP. Patients received 9 (42-day) cycles of bortezomib (1.3 mg/m2 SC) twice weekly in Cycle 1 (Weeks 1, 2, 4, 5) then once weekly in Cycles 2-9 (Weeks 1, 2, 4, 5); melphalan (9 mg/m2 PO) and prednisone (60 mg/m2 PO) once daily on Days 1-4 of each cycle. Patients in the D-VMP arm received DARA (16 mg/kg IV) once weekly in Cycle 1, once every three weeks in Cycles 2-9, and once every four weeks thereafter until disease progression or unacceptable toxicity. The primary endpoint was the rate of very good partial response or better (≥VGPR). Key secondary endpoints included progression-free survival (PFS), overall response rate (ORR), and safety. DARA PK and minimal residual disease (MRD) negativity rates were exploratory endpoints.
Results
A total of 220 patients (Chinese patients, n=167) were randomized to D-VMP (n=146) or VMP (n=74). Baseline characteristics were well balanced between arms; median age was 69 (range, 57-84) years and 48 (21.9%) patients had high-risk cytogenetics. At the time of data analysis (clinical cutoff 02 Jul 2020), 51 patients (35.4%) in the D-VMP arm completed 9 treatment cycles and received DARA monotherapy; 20 (28.2%) patients in the VMP arm had completed all 9 cycles of treatment. After a median follow-up of 12.3 (range, 0.0-29.3) months, ≥VGPR rate was significantly improved with D-VMP versus VMP overall (74.0% vs 43.2%; odds ratio 3.57; 95% CI 1.99-6.43; P<0.0001) and among Chinese patients (74.6% vs 45.3%; odds ratio 3.51; 95% CI 1.76-7.00; P=0.0003). ORR was 88.4% with D-VMP and 78.4% with VMP. Median PFS was not reached in the D-VMP arm and was 18.2 months in the VMP arm (HR 0.43; 95% CI 0.24-0.77; P=0.0033); the estimated 12-month PFS rate was 84.2% in the D-VMP arm versus 64.6% in the VMP arm. PK results for DARA (overall population n=144; Chinese patients n=114) were comparable between the overall population and Chinese patients. The most frequent (≥10%) grade 3/4 TEAEs for the D-VMP/VMP arms were thrombocytopenia (46.5%/45.1%), neutropenia (39.6%/50.7%), leukopenia (31.3%/36.6%), lymphopenia (30.6%/22.5%), pneumonia (29.2%/14.1%), anemia (24.3%/26.8%), and hypokalemia (13.2%/2.8%). TEAEs occurred at a similar rate in Chinese patients. Infusion-related reactions were observed in 44 patients (30.6%); the vast majority (n=41) were mild (grade 1 or 2). A total of 8 TEAE-related deaths (D-VMP, n=5; VMP, n=3) were reported. Additional data including the MRD negativity rate (10–5 threshold) will be presented.
Conclusion
The addition of DARA to VMP significantly improved efficacy outcomes for Asian patients with NDMM, consistent with results from the global ALCYONE trial. Safety profiles of D-VMP in an Asian population were also consistent with previously reported trials and no new safety concerns were identified. These data support the use of DARA plus VMP for the treatment of Asian and Chinese NDMM patients.
Keyword(s): Multiple myeloma, Pharmacokinetic, Safety
Abstract: EP1024
Type: E-Poster Presentation
Session title: Myeloma and other monoclonal gammopathies - Clinical
Background
Daratumumab (DARA), a human IgGκ monoclonal antibody that targets CD38, is approved for the treatment of NDMM in combination with standard-of-care regimens, including in combination with VMP based on results of the phase 3 ALCYONE trial. The phase 3 study OCTANS investigated the efficacy, safety, and pharmacokinetics (PK) of D-VMP in Asian NDMM patients.
Aims
To compare the efficacy, safety, and PK of D-VMP versus VMP in Asian and Chinese-only patients (NCT03217812).
Methods
Asian patients (from the following countries/regions: China, Hong Kong SAR, Taiwan, Korea, and Malaysia) with NDMM who were ineligible for autologous stem cell transplant were randomized (2:1) to D-VMP or VMP. Patients received 9 (42-day) cycles of bortezomib (1.3 mg/m2 SC) twice weekly in Cycle 1 (Weeks 1, 2, 4, 5) then once weekly in Cycles 2-9 (Weeks 1, 2, 4, 5); melphalan (9 mg/m2 PO) and prednisone (60 mg/m2 PO) once daily on Days 1-4 of each cycle. Patients in the D-VMP arm received DARA (16 mg/kg IV) once weekly in Cycle 1, once every three weeks in Cycles 2-9, and once every four weeks thereafter until disease progression or unacceptable toxicity. The primary endpoint was the rate of very good partial response or better (≥VGPR). Key secondary endpoints included progression-free survival (PFS), overall response rate (ORR), and safety. DARA PK and minimal residual disease (MRD) negativity rates were exploratory endpoints.
Results
A total of 220 patients (Chinese patients, n=167) were randomized to D-VMP (n=146) or VMP (n=74). Baseline characteristics were well balanced between arms; median age was 69 (range, 57-84) years and 48 (21.9%) patients had high-risk cytogenetics. At the time of data analysis (clinical cutoff 02 Jul 2020), 51 patients (35.4%) in the D-VMP arm completed 9 treatment cycles and received DARA monotherapy; 20 (28.2%) patients in the VMP arm had completed all 9 cycles of treatment. After a median follow-up of 12.3 (range, 0.0-29.3) months, ≥VGPR rate was significantly improved with D-VMP versus VMP overall (74.0% vs 43.2%; odds ratio 3.57; 95% CI 1.99-6.43; P<0.0001) and among Chinese patients (74.6% vs 45.3%; odds ratio 3.51; 95% CI 1.76-7.00; P=0.0003). ORR was 88.4% with D-VMP and 78.4% with VMP. Median PFS was not reached in the D-VMP arm and was 18.2 months in the VMP arm (HR 0.43; 95% CI 0.24-0.77; P=0.0033); the estimated 12-month PFS rate was 84.2% in the D-VMP arm versus 64.6% in the VMP arm. PK results for DARA (overall population n=144; Chinese patients n=114) were comparable between the overall population and Chinese patients. The most frequent (≥10%) grade 3/4 TEAEs for the D-VMP/VMP arms were thrombocytopenia (46.5%/45.1%), neutropenia (39.6%/50.7%), leukopenia (31.3%/36.6%), lymphopenia (30.6%/22.5%), pneumonia (29.2%/14.1%), anemia (24.3%/26.8%), and hypokalemia (13.2%/2.8%). TEAEs occurred at a similar rate in Chinese patients. Infusion-related reactions were observed in 44 patients (30.6%); the vast majority (n=41) were mild (grade 1 or 2). A total of 8 TEAE-related deaths (D-VMP, n=5; VMP, n=3) were reported. Additional data including the MRD negativity rate (10–5 threshold) will be presented.
Conclusion
The addition of DARA to VMP significantly improved efficacy outcomes for Asian patients with NDMM, consistent with results from the global ALCYONE trial. Safety profiles of D-VMP in an Asian population were also consistent with previously reported trials and no new safety concerns were identified. These data support the use of DARA plus VMP for the treatment of Asian and Chinese NDMM patients.
Keyword(s): Multiple myeloma, Pharmacokinetic, Safety