Response was assessed using EBMT criteriar with the addition of VGPR.r
Patients were heavily pre-treated: 77% received RAD as third or fourth line; 84% had prior autologous stem cell transplantation (12% had auto followed by allo-transplantation); 84% had prior anthracycline based regimens; 57% had prior bortezomib. 32% had relapsed-refractory disease.
FISH was performed on 37 patients in whom 13q- was found in 15, t(4;14) in 4 and 17p- in 5 patients.
Efficacy can be summarised in the following table of ‘best response’, based on intention to treat and dose levels (level 5+GCSF vs rest):
© Blood 2009
ORR (CR+VGPR+PR) was seen in 48 out of 66 patients, (73%, 95% CI, 60-83%), including 10 patients achieving CR (15%), and an additional 30 patients achieving VGPR (45%). Only 5 patients had progressive disease.
There was a large difference in ORR between Level 5+G versus the rest (Level 1 plus G to Level 4 plus G): CR+VGPR 74% vs 25%. Note there was no CR seen in Levels 1 to 4.
ORR was 71% in relapsed-refractory patients, compared to 75% in relapsed patients.
Median time to progression (TTP) was 45 weeks for the whole group, and one year survival probability was 88%. (Figure 1). No statistically significant difference in TTP was seen between CR (51.8 weeks), VGPR (46.2 weeks) and PR (45.4 weeks) patients. This may be due to small numbers in any category.
On multivariate analysis, only beta-2-microglobulin of >297.5nmol/L was associated with significantly shortened TTP (HR 2.55, 95% CI 1.29-5.02, p<0.007). Of the cytogenetic FISH findings, only 17p- (despite only 5 patients with this finding) had significantly shorter median TTP and lower ORR. Prior therapies, including stem cell transplant, thalidomide and bortezomib, were not significantly associated with outcome.
© Blood 2009