Bortezomib and Melphalan (Bor/MEL) Conditioning for Patients with Multiple Myeloma Undergoing Single Autologous Stem Cell Transplantation

Abstract

Introduction The treatment of MM patient has improved over the past 10 years, with median PFS approaching 4 years after autologous stem cell transplant (ASCT). Recently, Roussel et al reported a phase 2 trial combining melphalan and bortezomib as conditioning regimen. In this trial, 70% of patients attained VGPR or better with at least 32% of patients in CR after a single course of HDT prepared by the Bortezomib/Melphalan (Bor/MEL) conditioning regimen, regardless of the type of induction therapy.Methods We retrospectively reviewed all cases treated with bortezomib in combination with Melphalan 200 mg/m2 (Bor/MEL) as transplantation conditioning regimen in patients with MM. Bortezomib was administered intravenously at 1 mg/m2 -1.3 mg/m2 on days −5, −2, 1, and 4. Melphalan was administered intravenously at 200 mg/m2 and stem cells were infused on day 0. In an attempt to determine whether this Bor/MEL conditioning regimen was superior to Melphalan alone (MEL), we secondarily compared our cohort with patients treated at the same time where this strategy was not used. Two-sided Fisher exact test was used to test for differences between categorical variables. P value of <0.05 was considered significant. Survival curves were constructed according to the Kaplan-Meier method and compared using the log rank test.Results Fifty-seven patients with documented symptomatic MM undergoing ASCT using Bor/MEL conditioning from July 2010 to February 2014 were identified as well as 57 more in the control arm (MEL only). Clinical characteristics are shown in Table 1. At a median follow-up of 24.2 months in the Bor/MEL group and 20.9 months in the MEL group, 9 and 7 patients have died respectively (p=0.39). Seventeen patients in the Bor/MEL group (29%) and 24 pts in the MEL group (42%) had already progressed. (p=0.121) The CR/nCR rate was higher for the group treated with Bor/MEL and there was a trend of higher VGPR or better rate in this group as well. (p=0.024 and 0.07) (Table 2) Median Overall survival has not been reached in both groups and mean OS for Bor/MEL is 38.7 months versus 44.9 (p=0.66). Median OS was shorter for the group with HR cytogenetics treated with either Bor/MEL or MEL conditioning regimens (20 months vs NR) p=0.0001 while the median progression-free survival (PFS) was 29 months in the Bor/MEL group versus 25.1 in the MEL alone group. (p=0.5653) In addition, Median PFS was shorter in the group of patients with HR disease, 13 months versus 32.8 months in the SR group (p=0.0003) regardless of the use of either Bor/MEL or MEL alone.In conclusion, Bor/MEL conditioning regimen increases the rate of CR/nCR compared to MEL alone for patients with symptomatic MM undergoing ASCT. However, Median OS and PFS are shorter in the group of patients with HR disease even with the use of this strategy. Novel approaches in the HR disease should be considered such as continuous treatment and perhaps lenalidomide/bortezomib combinations in the maintenance setting.Table 1Clinical CharacteristicsCharacteristicBor/MEL, N=57MEL, N=57p=valueAge (median)58600.429GenderMale Female35 (61%) 22 (49%)35 (61%) 22 (49%)0.576Hb (g/L)1141170.288Calcium (µmol/L)2.212.270.227Creatinine (µmol/L)73760.399B2microglobulin (µmol/L)3.242.50.415Albumin (g/L)31350.098Stage I Stage II Stage III11 31 1519 31 70.080M-spike (g/L)3430.20.537LDH (IU/L)1941680.188BMPC (%)43350.356Heavy chain:IgG IgA FLC only37 12 537 8 110.506Light chain:Kappa Lambda Biclonal37 19 142 14 10.356High risk Standard risk12 4513 440.500Table 2Induction chemotherapy and response rateCharacteristicBor/MELMELP= valueInduction chemotherapy-CyBORD -Velcade and Dexamethasone -RVD Others19 (33%) 26 (45%) 12 (22%)10 (17%) 31 (54%) 11 (19%) 5 (10%)0.142Induction Response³VGPR 24 (42%)22 (38%)0.394Day-100 response³VGPR CR/nCR VGPR PR <PR ³VGPR in HR disease86% 12/13 (43%) 25 (43%) 6 (10%) 1 (1.8%) 91.6% (11/12)78% 5/9 (24%) 31 (54%) 11 (19%) 1 (1.8%) 69% (9/13)0.230 0.024 0.070MaintenanceLenalidomide None47 1045 110.580ConsolidationRVD None14 436 510.042CyBORD: Cyclophosphamide, bortezomib and dexamethasone; RVD: Lenalidomide, bortezomib and dexamethasone DisclosuresJimenez Zepeda:Janssen Ortho: Honoraria. Bahlis:Celgene: Honoraria, Research Funding.