US Food and Drug Administration and European Medicines Agency approvals sought for new combined drug regimens in multiple myeloma  

NCT reference

NCT02541383

Drug combination

Dara-VTd

VTd 

Patient setting

Transplant eligible NDMM

Trial phase

Phase III

Trial design

Dara-VTd versus VTd

N

1,085

Dosing schedule

Four cycles of VTd induction +/- daratumumab (16 mg/kg), high-dose therapy and ASCT followed by two cycles of VTd consolidation +/- daratumumab (16 mg/kg)

Primary endpoint

sCR

Efficacy

sCR (dara-VTd vs VTd):

28.9% vs 20.3%

(odds ratio: 1.60, 95% CI, 1.21–2.12, P ≤ 0.001)

Safety

Safety profile of dara-VTd consistent with that of VTd and daratumumab alone.

NCT reference

NCT02252172

Drug combination

DRd 

Rd 

Patient setting

Transplant ineligible NDMM

Trial phase

Phase III

Trial design

DRd versus Rd

N

737

Dosing schedule

Rd: oral lenalidomide (25 mg) on days 1–21 of a 28-day cycle with 40 mg dexamethasone once per week.

DRd: As per Rd arm with the addition of intravenous daratumumab (16 mg/kg) once weekly for cycles 1–2, every 2 weeks for cycles 3–6 and every 4 weeks for cycle 7 onwards until disease progression, unacceptable toxicity or study end

Primary endpoint

PFS

Efficacy

(Given as DRd vs Rd)

Median follow-up: 28 months

Median PFS: not reached vs 31.9 months

≥ CR: 47.6% vs 24.7%

ORR: 93% vs 81%

Risk of reduction of disease progression or death with DRd vs Rd alone: 44% (HR 0.56, 95% CI, 0.43–0.73, P < 0.0001)

Safety

In the DRd arm, there were higher rates (≥5% difference) of grade 3/4 pneumonia, neutropenia and leukopenia

Safety profile is in line with previously reported daratumumab studies