Page 235 - Haematologica April 2020

First-line therapy in elderly MM patients
95% CI: 20.9-28.6) or Rd-R (18.6 months, 95% CI: 16- 22.4) (HR=0.81, P=0.07). At 5 years, 15% and 18% of patients were alive and free from progression in the VMP and Rd-R groups, respectively. In the subgroup analyses (Figure 1), no clear differences in PFS were noted between the VMP and Rd-R groups according to age (in patients ≤75 years, HR=0.80; in patients >75 years, HR=0.84, inter- action P=0.85), Karnofsky PS (score 90-100, HR=0.73; score 70-80, HR= 0.86, interaction P=0.43), ISS stage (stage I, HR=0.73; stage II/III, HR=0.85, interaction P=0.55) and the presence of extramedullary disease (yes, HR=0.75; no, HR=0.82, interaction P=0.78). As far as concerns FISH- determined cytogenetic risk, no difference in PFS was observed among standard-risk patients between the VMP and Rd-R groups (HR=0.96, 95% CI: 0.73-1.28), whereas in high-risk patients, a significant benefit was observed with VMP in comparison with Rd-R (HR=0.54, 95% CI: 0.34-0.84; interaction P=0.03). The advantage of VMP over Rd-R in high-risk patients was confirmed in the sub- groups of single high-risk cytogenetic abnormalities, including del(17p) (HR=0.59, 95% CI: 0.32-1.09), t(4;14) (HR=0.50, 95% CI: 0.27-0.93) and t(14;16) (HR=0.35, 95% CI: 0.09-1.42) (Online Supplementary Figure S1).
The median OS in the overall population was 66.4 months (95% CI: 57.3-79.7); the median OS was not sig- nificantly different between patients treated with VMP (71 months; 95% CI: 58.2-not reached) or Rd-R (62 months, 95% CI: 48.2-83.3) (HR=0.85; P=0.28), with an equivalent proportion of patients alive at 5 years (55% vs. 51%, respectively). In the subgroup analysis (Figure 2), patients ≤75 years old benefited more from VMP than Rd- R (HR=0.71, 95% CI: 0.51-1.00), whereas patients >75
years old benefited more from Rd-R (HR=1.29, 95% CI: 0.79-2.13; interaction P=0.04). Similarly to PFS, no signifi- cant difference in OS was noted among standard-risk patients between those treated with VMP or Rd-R (HR=1.08, 95% CI: 0.74-1.58), but among patients with high-risk cytogenetics, an OS advantage was reported for VMP-treated patients over those treated with Rd-R (HR=0.73, 95% CI: 0.42-1.26) and those with missing data. The advantage for VMP over Rd-R in high-risk patients was confirmed in the subgroups of single high- risk cytogenetic abnormalities, including del(17p) (HR=0.81, 95% CI: 0.38-1.71), t(4;14) (HR=0.74, 95% CI: 0.35-1.56), and t(14;16) (HR=0.73, 95% CI: 0.13-4.05) (Online Supplementary Figure S2).
Multivariate Cox models with three-way interaction were performed to better evaluate the relationship between treatment regimen (VMP vs. Rd-R), age (≤75 vs. >75 years) and cytogenetic risk (standard vs. high). This analysis confirmed the absence of difference in PFS between VMP and Rd-R according to age in the standard- risk group, while confirmed the PFS benefit from VMP over Rd-R in high-risk patients (interaction P=0.03). With regards to OS, older (>75 years), standard-risk patients seemed to benefit more from Rd-R than from VMP (HR=1.81), while the OS advantage from VMP was con- firmed in younger (≤75 years), standard-risk patients (HR=0.83). In high-risk patients, the OS benefit was con- firmed irrespective of age (≤75 years, HR=0.75; >75 years, HR=0.65) (Table 3).
To better investigate the comparison between VMP and Rd-R and the effect of cytogenetics and age we performed a multiple imputation analysis for missing cytogenetics
Figure 1. Subgroup analysis of progression-free survival in the intention-to-treat population for patients treated with VMP or Rd-R. VMP: bortezomib-melphalan- prednisone; Rd-R: lenalidomide-dexamethasone followed by lenalidomide maintenance; HR: hazard ratio; 95% CI: 95% confidence interval; ISS: International Staging System.
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