Contributions
Abstract: S189
Type: Oral Presentation
Session title: New diagnostic and therapeutic approaches in multiple myeloma and AL amyloidosis
Background
Light chain amyloidosis (AL) is a systemic plasma cell disease where organ impairment and death can occur due to insoluble amyloid fibrils deposition. Adding subcutaneous daratumumab to the standard of care (bortezomib, cyclophosphamide, and dexamethasone [VCd]) in ANDROMEDA (NCT03201965) led to superior outcomes versus VCd alone (primary results), including greater hematologic complete response (CR) rates and an acceptable safety profile. In January 2021, Daratumumab+VCd was approved for patients with newly diagnosed AL amyloidosis.
Aims
To report updated primary results with longer follow up from the ANDROMEDA study.
Methods
ANDROMEDA is an ongoing open-label, randomized, active-controlled, phase 3 trial. Adult patients with newly diagnosed AL amyloidosis were randomly assigned 1:1 to receive daratumumab+VCd or VCd for six 28-day cycles. Written informed consent was obtained from all patients. Bortezomib dosed at 1.3 mg/m2, cyclophosphamide at 300 mg/m2 (up to 500 mg weekly), and dexamethasone at 40 mg were administered every week. Subcutaneous daratumumab was administered once weekly in cycles 1 and 2 and every 2 weeks in cycles 3 to 6. Patients in the daratumumab+VCd arm received only subcutaneous daratumumab after cycle 6, every 4 weeks (up to a total of 24 cycles from first dose). Disease status was assessed every 4 weeks in cycles 1 to 6 and every 8 weeks thereafter. Overall hematologic CR rate (intent-to-treat population) was the primary endpoint. Time to hematologic response, major organ deterioration progression-free survival, survival, organ response rate, and safety were the secondary endpoints.
Results
Among 388 randomized patients, 195 received daratumumab+VCd and 193 received VCd alone. At the November 2020 cutoff, the median duration of treatment for daratumumab+VCd and VCd arms was 18.5 and 5.3 months, respectively, and 78 patients (40%) in the daratumumab+VCd arm were still receiving treatment. The overall hematologic CR rate in the daratumumab+VCd arm (59%) was significantly higher versus the VCd arm (19%; odds ratio [95% CI], 5.9 [3.7–9.4]; P<0.0001). More patients achieved a very good partial response or better (≥VGPR) with daratumumab+VCd (79%) compared with VCd alone (50%; odds ratio [95% CI], 3.7 [2.4–5.9]; P<0.0001). Among patients who responded, the median time from randomization to ≥VGPR was shorter in the daratumumab+VCd arm (0.56 months) versus the VCd arm (0.82 months). Greater cardiac response rates were achieved at 6 months with daratumumab+VCd (42%) versus VCd alone (22%) and at 12 months (57% versus 28%); similarly, renal response rates were greater with daratumumab+VCd (54%) versus VCd alone (27%) at 6 months and at 12 months (57% versus 27%). Overall, 71 patients died (daratumumab+VCd, 31; VCd, 40). Starting cycle 7, no grade 3/4 treatment-emergent adverse events occurred in ≥5% of patients in the daratumumab+VCd arm. After cycle 6, no systemic administration-related reactions were reported with in the daratumumab+VCd. Major organ deterioration progression-free survival is scheduled to be updated after approximately 200 events.
Conclusion
Updated results from the ANDROMEDA study further support that in patients with newly diagnosed AL amyloidosis, the daratumumab+VCd combination is clinically superior compared with VCd alone. Following its recent approval, the daratumumab+VCd combination represents a new standard of care for patients with AL amyloidosis.
Keyword(s): Amyloidosis
Abstract: S189
Type: Oral Presentation
Session title: New diagnostic and therapeutic approaches in multiple myeloma and AL amyloidosis
Background
Light chain amyloidosis (AL) is a systemic plasma cell disease where organ impairment and death can occur due to insoluble amyloid fibrils deposition. Adding subcutaneous daratumumab to the standard of care (bortezomib, cyclophosphamide, and dexamethasone [VCd]) in ANDROMEDA (NCT03201965) led to superior outcomes versus VCd alone (primary results), including greater hematologic complete response (CR) rates and an acceptable safety profile. In January 2021, Daratumumab+VCd was approved for patients with newly diagnosed AL amyloidosis.
Aims
To report updated primary results with longer follow up from the ANDROMEDA study.
Methods
ANDROMEDA is an ongoing open-label, randomized, active-controlled, phase 3 trial. Adult patients with newly diagnosed AL amyloidosis were randomly assigned 1:1 to receive daratumumab+VCd or VCd for six 28-day cycles. Written informed consent was obtained from all patients. Bortezomib dosed at 1.3 mg/m2, cyclophosphamide at 300 mg/m2 (up to 500 mg weekly), and dexamethasone at 40 mg were administered every week. Subcutaneous daratumumab was administered once weekly in cycles 1 and 2 and every 2 weeks in cycles 3 to 6. Patients in the daratumumab+VCd arm received only subcutaneous daratumumab after cycle 6, every 4 weeks (up to a total of 24 cycles from first dose). Disease status was assessed every 4 weeks in cycles 1 to 6 and every 8 weeks thereafter. Overall hematologic CR rate (intent-to-treat population) was the primary endpoint. Time to hematologic response, major organ deterioration progression-free survival, survival, organ response rate, and safety were the secondary endpoints.
Results
Among 388 randomized patients, 195 received daratumumab+VCd and 193 received VCd alone. At the November 2020 cutoff, the median duration of treatment for daratumumab+VCd and VCd arms was 18.5 and 5.3 months, respectively, and 78 patients (40%) in the daratumumab+VCd arm were still receiving treatment. The overall hematologic CR rate in the daratumumab+VCd arm (59%) was significantly higher versus the VCd arm (19%; odds ratio [95% CI], 5.9 [3.7–9.4]; P<0.0001). More patients achieved a very good partial response or better (≥VGPR) with daratumumab+VCd (79%) compared with VCd alone (50%; odds ratio [95% CI], 3.7 [2.4–5.9]; P<0.0001). Among patients who responded, the median time from randomization to ≥VGPR was shorter in the daratumumab+VCd arm (0.56 months) versus the VCd arm (0.82 months). Greater cardiac response rates were achieved at 6 months with daratumumab+VCd (42%) versus VCd alone (22%) and at 12 months (57% versus 28%); similarly, renal response rates were greater with daratumumab+VCd (54%) versus VCd alone (27%) at 6 months and at 12 months (57% versus 27%). Overall, 71 patients died (daratumumab+VCd, 31; VCd, 40). Starting cycle 7, no grade 3/4 treatment-emergent adverse events occurred in ≥5% of patients in the daratumumab+VCd arm. After cycle 6, no systemic administration-related reactions were reported with in the daratumumab+VCd. Major organ deterioration progression-free survival is scheduled to be updated after approximately 200 events.
Conclusion
Updated results from the ANDROMEDA study further support that in patients with newly diagnosed AL amyloidosis, the daratumumab+VCd combination is clinically superior compared with VCd alone. Following its recent approval, the daratumumab+VCd combination represents a new standard of care for patients with AL amyloidosis.
Keyword(s): Amyloidosis