The US Food and Drug Administration (FDA) has approved bortezomib (Velcade) for use in previously untreated patients with mantle cell
lymphoma (MCL).
This is the first drug to be approved in the US for previously untreated patients with MCL.
The approval extends the utility of bortezomib beyond relapsed or refractory MCL, for which it has been approved since 2006.
The new approval is based on results of a phase 3 trial.
The study was a comparison of VcR-CAP (bortezomib, rituximab, cyclophosphamide, doxorubicin, and prednisone) and R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) in 487 patients newly diagnosed with stage II, III, or IV MCL.
Survival and response
VcR-CAP demonstrated a 59% relative improvement in the study’s primary endpoint of progression-free survival. At a median follow-up of 40 months, the median progression-free survival was 25 months in the VcR-CAP arm and 14 months in the R-CHOP arm (hazard ratio [HR]=0.63, P<0.001).
However, there was no significant improvement in overall survival. The median overall survival was not reached in the VcR-CAP arm and was 56.3 months in the R-CHOP arm (HR=0.80; P=0.173).
Patients in the VcR-CAP arm had a higher rate of complete response/unconfirmed complete response than those in the R-CHOP arm—53% and 42%, respectively (P=0.007). But there was no significant difference in overall response—92% and 90%, respectively (P=0.275).
The time to progression was significantly longer in the VcR-CAP arm—30.5 months, compared to 16.1 months in the R-CHOP arm (HR=0.58; P<0.001). And the median time to subsequent treatment was significantly longer in the VcR-CAP arm—44.5 months vs 24.8 months (HR 0.50; P<0.001).
Adverse events
VcR-CAP was associated with additional but manageable toxicity compared to R-CHOP.
Serious adverse events were reported in 38% of patients in the VcR-CAP arm and 30% in the R-CHOP arm. Grade 3 or higher adverse events were reported in 93% and 85%, respectively.
There were similar rates of all-grade peripheral neuropathy between the VcR-CAP arm and the R-CHOP arm—30% and 29%, respectively. But the rate of grade 3 or higher peripheral neuropathy was significantly higher in the VcR-CAP arm—7.5% vs 4.1%.
The incidence of all-grade thrombocytopenia was substantially higher in the VcR-CAP arm than the R-CHOP arm—72% and 19%, respectively. But there was no significant difference in bleeding events—6% and 5%, respectively.
The incidence of all-grade neutropenia was 88% in the VcR-CAP arm and 74% in the R-CHOP arm. The rate of grade 3 or higher febrile neutropenia was 14% and 15%, respectively, and the rate of infection was 60% and 46%, respectively.
These data were presented at ASCO 2014 as abstract 8500.
Bortezomib is marketed as Velcade by Millennium/Takeda and Janssen Pharmaceutical Companies. Millennium is responsible for commercialization in the US, and Janssen Pharmaceutical Companies are responsible for commercialization in the rest of the world.
For more details on the drug, visit www.velcade.com.
