Proteasome inhibitor maintenance therapy

In a prospective randomized trial of 656 newly diagnosed patients with at least a PR after standard induction therapy followed by autologous SCT, ixazomib (the oral proteasome inhibitor) was compared with placebo.[141]

In a prospective randomized trial of 656 newly diagnosed patients with at least a PR after standard induction therapy followed by autologous SCT, ixazomib (the oral proteasome inhibitor) was compared with placebo.[141]

With a median follow-up of 31 months, the ixazomib maintenance improved medial PFS, 26.5 months (95% CI, 23.7−33.8) versus 21.3 months (95% CI, 18.0−24.7) (HR, 0.72; 95% CI, 0.58−0.89; P = .0023).[141][Level of evidence B1] There was no increase in second malignancies with the proteasome inhibitor (3% for both groups).

In 511 previously untreated patients not eligible for transplant and aged 65 years or older, a randomized comparison of bortezomib, melphalan, prednisone, thalidomide and subsequent maintenance using bortezomib plus thalidomide versus VMP (with no maintenance) showed superiority of the arm with thalidomide and bortezomib during induction and maintenance.

In 511 previously untreated patients not eligible for transplant and aged 65 years or older, a randomized comparison of bortezomib, melphalan, prednisone, thalidomide and subsequent maintenance using bortezomib plus thalidomide versus VMP (with no maintenance) showed superiority of the arm with thalidomide and bortezomib during induction and maintenance.

With a median follow-up of 47 months, the 3-year PFS rate was 55% versus 33% (P < .01), and the 5-year OS rate was 59% versus 46% (P = .04).[142][Level of evidence A1]

In 511 previously untreated patients not eligible for transplant and aged 65 years or older, a randomized comparison of bortezomib, melphalan, prednisone, thalidomide and subsequent maintenance using bortezomib plus thalidomide versus VMP (with no maintenance) showed superiority of the arm with thalidomide and bortezomib during induction and maintenance.

Because of trial design, it is unclear whether the improved results were caused by the addition of thalidomide during the induction or by the use of maintenance therapy with bortezomib and thalidomide.