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ASH 2012: Dr. Palumbo- Overall Survival Benefit for Bortezomib-Melphalan-Prednisone-Thalidomide Followed by Maintenance with Bortezomib-Thalidomide (VMPT-VT) Versus Bortezomib-Melphalan-Prednisone (VMP) in Newly Diagnosed Multiple Myeloma Patients
Antonio Palumbo, MD
University of Torino
Torino, Italy
12.03.12
Program: Oral and Poster Abstracts
Type: Oral
Session: 653. Myeloma - Therapy, excluding Transplantation I
Sunday, December 9, 2012: 4:45 PM
Thomas Murphy Ballroom 2-3, Level 5, Building B (Georgia World Congress Center)

Antonio Palumbo, MD1, Sara Bringhen1*, Davide Rossi, MD2*, Maide Cavalli, MD2*, Roberto Ria, MD2*, Silvia Gentilini, MD2*, Francesca Patriarca2*, Chiara Nozzoli, MD2*, Anna Levi, MD2*, Tommasina Guglielmelli, MD2*, Giulia Benevolo, MD2*, Donatella Vincelli, MD2*, Luca Baldini2*, Fortunato Morabito, MD2*, Mariella Grasso, MD2*, Roberto Marasca, MD2*, Manuela Rizzo, MD2*, Chiara Pautasso, Pharm D1*, Antonietta Pia Falcone, MD2*, Daniela Gottardi, MD2*, Vittorio Montefusco, MD2*, Caterina Musolino, MD2*, Clotilde Cangialosi, MD2*, Giovanna Mansueto, MD2*, Anna Marina Liberati, MD2*, Valeria Magarotto, MD1*, Paola Omedè, PhD1*, Pellegrino Musto, MD2*, Maria Teresa Petrucci, MD2* and Mario Boccadoro, MD1*

1Myeloma Unit, Division of Hematology, University of Torino, Torino, Italy
2Italian Multiple Myeloma Network, GIMEMA, Italy

Background: In a multicenter phase 3 randomized trial, VMPT-VT was superior to VMP for response rates, progression-free survival and time to next treatment (Palumbo A, et al. J Clin Oncol 2010). Here we report an updated analysis on survival after 4 years of follow-up.

Methods: Patients (N=511) were randomly assigned to receive nine 6-week cycles of VMPT-VT (induction: bortezomib 1.3 mg/m2, d 1, 4, 8, 11, 22, 25, 29, 32, cycles 1–4, d 1, 8, 22, 29, cycles 5–9; melphalan 9 mg/m2 d 1–4, prednisone 60 mg/m2, d 1–4, thalidomide 50 mg d 1-42; maintenance: bortezomib 1.3 mg/m2 every 14 days and thalidomide 50 mg/day up to 2 years) or VMP alone. After the inclusion of 139 patients, the protocol was amended: both VMPT-VT and VMP induction schedules were changed to nine 5-week cycles and bortezomib schedule was modified to weekly administration (1.3 mg/m2 d 1,8,15,22, all cycles).

Results: After a median follow-up of 47.2 months, median OS was not reached in the VMPT-VT arm and was 58.2 months in the VMP arm; 5-year OS rates were 59.3% and 45.9%, respectively (HR 0.74, p=0.04), with 26% reduced risk of death for patients receiving VMPT-VT (Figure-panel A). This benefit was more evident in patients younger than 75 years (5-year rates 67.8% for VMPT-VT vs 49.9% for VMP, HR 0.63, p=0.01, Figure-panel B) and in patients in complete response (CR) after induction (5-year rates 81.4% for VMPT-VT vs 48.2% for VMP, HR 0.38, p=0.006, Figure-panel C) while no significant differences were evident in patients with standard- or high-risk features detected by FISH (HR 0.99, p=0.99). A 1-year landmark analysis for patients completing induction was performed: the 4-year OS was 64.6% in the VMPT-VT group and 49.7% in the VMP group, with 33% reduced the risk of death for patients receiving VT maintenance (HR 0.67, p=0.02). Forty-nine percent of VMPT-VT and 70% of VMP patients relapsed and received subsequent salvage therapies; there was no difference in survival from relapse in the two groups (2-year OS rates 40.7% vs 50.2%,HR 1.11, p=0.54).

The median duration of VT maintenance was 23.8 months. During VT maintenance 7% of patients experienced grade 3-4 peripheral neuropathy, 5% grade 3-4 hematological toxicity, 3% grade 3-4 infection and 12% discontinued due to adverse events. Second primary malignancies were reported in 7/254 patients in the VMPT-VT group and 7/257 patients in the VMP group. These corresponded to incidence rates of 0.9 and 1.05 per 100 patient-years, respectively, and were consistent with background incidence rates in the general population (aged 65–74 years 1.9, aged ≥ 75 years 2.3, SEER database).

Conclusions: VMPT-VT significantly prolonged OS compared with VMP, especially in patients younger than 75 years and in patients achieving CR after induction. In patients 67-75 years of age, VMPT-VT reduced the risk of death by 37% and it should be considered a new standard of care.


 


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