Bortezomib-based Induction Improves PFS, OS in High-risk Newly Diagnosed Multiple Myeloma
A relevant prognostic factor for patients with MM is cytogenetic abnormalities, but the effect these abnormalities may have among high-risk transplant-ineligible patients treated with first-line borte
|The following article features coverage from the American Society of Hematology (ASH) 2017 meeting. Click here to read more of Cancer Therapy Advisor's conference coverage.|
High-risk patients with newly diagnosed multiple myeloma (NDMM) who receive bortezomib-based induction therapy have improved progression-free survival (PFS) and overall survival (OS) compared with patients who receive lenalidomide-based therapy, according to an oral presentation at the 2017 American Society of Hematology (ASH) Annual Meeting in Atlanta, Georgia.1
A relevant prognostic factor for patients with MM is cytogenetic abnormalities determined by fluorescence in situ hybridization (FISH), but the effect these abnormalities may have among high-risk transplant-ineligible patients treated with first-line bortezomib or lenalidomide had not previously been investigated.
In the phase 3 GIMEMA-MM-03-05-trial (ClinicalTrials.gov Identifier: NCT01063179), patients were randomly assigned to receive bortezomib, melphalan, prednisone, and thalidomide for 9 cycles, followed by maintenance bortezomib plus thalidomide (VMPT-VT), or bortezomib, melphalan, and prednisone (VMP) for 9 cycles without maintenance.
For the phase 3 EMN01-trial (ClinicalTrials.gov Identifier: NCT01093196), patients were randomly assigned to receive cyclophosphamide, prednisone, and lenalidomide (CPR), melphalan, prednisone, and lenalidomide (MPR), or lenalidomide plus low-dose dexamethasone (Rd) for 9 cycles. All study patients received maintenance therapy with lenalidomide with or without prednisone.
All 1165 study patients underwent cytogenetic testing by FISH and were stratified according to their International Myeloma Working Group cytogenetic risk criteria; patients with del(17p), t(4;14), or t(14;16) were considered to be high risk, all other patients were standard risk.
Nine-hundred and two patients had evaluable cytogenetic profiles, of whom 27% and 73% were characterized as high risk and standard risk, respectively. The median follow-up of patients treated with bortezomib was 72.3 months and 63.6 months for patients treated with lenalidomide.
The median PFS was 30.8 months compared with 14.8 months in bortezomib-treated patients vs lenalidomide-treated patients who were high risk, respectively (hazard ratio [HR], 0.54; 95% CI, 0.41-0.72), and 29.1 months compared with 22.1 months among patients who were standard risk, respectively (HR: 0.87; 95%; CI, 0.72-1.05).
Median OS was 62.4 months among high-risk patients in the bortezomib arm vs 43.2 months in the lenalidomide arm (HR, 0.68; 95% CI, 0.47-0.96); median OS was 78.1 months among standard-risk patients in the bortezomib arm vs not reached in the lenalidomide arm (HR, 1.06; 95% CI, 0.82-1.36) (interaction-P = .04).
Median PFS was 18.0 vs 12.9 months among patients with del(17p) who received bortezomib vs lenalidomide, respectively (HR, 0.71; 95% CI; 0.49-1.04). Median PFS was 31.5 vs 15.2 months among patients with t(4;14) who received bortezomib vs lenalidomide, respectively (HR, 0.41; 95% CI, 0.27-0.62). Median PFS was 36.2 vs 9.8 months among patients with t(14;16) who received bortezomib vs lenalidomide, respectively (HR, 0.34; 95% CI, 0.16-0.76).
The authors concluded that “[t]hese results support VMP induction as a standard treatment option for patients with NDMM who are ineligible for transplant with [high-risk] cytogenetics.”
Read more of Cancer Therapy Advisor's coverage of the American Society of Hematology (ASH) 2017 meeting by visiting the conference page.
- Larocca A, Offidani M, Musto P, et al. Impact of bortezomib- or lenalidomide-based induction treatment on high risk cytogenetic transplant-ineligible patients with newly diagnosed multiple myeloma enrolled in the GIMEMA-MM-0305 and ENM01 trials. Oral presentation at: American Society of Hematology 59th Annual Meeting & Exposition; December 9-12, 2017; Atlanta, GA.