Positive EMA CHMP opinion for two new triplet regimens in multiple myeloma

NCT reference

NCT00644228

Phase

III

Number of patients (N)

525

Randomization

1:1 - VRd:Rd

Dosing VRd

Eight 21-day cycles

IV bortezomib 1.3 mg/m², on days 1, 4, 8 and 11

Oral lenalidomide 25 mg, on days 1–14

Oral dexamethasone 20 mg, on days 1, 2, 4, 5, 8, 9, 11 and 12

Dosing Rd

Six 28-day cycles

Oral lenalidomide 25 mg, on days 1–21

Oral dexamethasone 40 mg on days 1, 8, 15 and 22

Maintenance

Oral lenalidomide 25 mg once daily for 21 days

Oral dexamethasone 40 mg once daily for days 1, 8, 15 and 22 of each 28-day cycle

Efficacy

(given as VRd vs Rd)

Median PFS: 43 vs 30 months (HR 0.712, 96% CI, 0.56–0.906, P = 0.0018)

Median OS: 75 vs 64 months (HR 0·709, 95% CI 0·524–0·959, P = 0.025)

ORR: 82% vs 72%

CR: 16% vs 8%

Safety

Consistent with the individual safety profiles of each drug alone

Most common grade ≥3 events that were partially attributable to treatment:

• Hematological: anemia, lymphopenia, neutropenia and thrombocytopenia
• Non-hematological: fatigue, sensory neuropathy, hyperglycemia, thrombosis or embolism, hypokalemia, muscle weakness, diarrhea and dehydration

Neurological events: more frequent in VRd group compared to Rd group (33% vs 11%, P < 0.0001)

NCT reference

NCT01734928

Phase

III

Number of patients (N)

559

71% vs 69% of patients were refractory to lenalidomide (PVd vs Vd arm)

Randomization

1:1 - PVd:Vd – patients were stratified based on age, anti-myeloma treatment and β-microglobulin levels

Dosing PVd

21-day cycles:

Pomalidomide 4 mg daily on days 1–14

Bortezomib 1.3 mg/m² on days 1, 4, 8 and 11 of cycles 1–8 and on days 1 and 8 of cycle 9 onwards:

Dexamethasone 20 mg (dose was 10 mg for patients > 75 years old) on the same day and the day after bortezomib in all 21-day cycles

Efficacy

(given as PVd vs Vd)

Median follow-up: 16 months

Median PFS: 11.2 vs 7.1 months

39% reduction in the risk of disease progression or death (HR 0.61, 95% CI, 0.49–0.77, P ≤ 0.001)

Subgroup analysis in patients with one prior line of therapy

Median PFS: 20.73 vs 11.63 months (HR 0.54, P = 0.0027)

Benefit of PVd was independent of whether patients were refractory or non-refractory to prior lenalidomide

Safety

Consistent with the individual safety profiles of each drug alone