Bortezomib Overcomes Usual Prognosis Factor in Patients with Multiple Myeloma (MM) Having High Dose Therapy (HDT)

Abstract 3104

The outcome for MM patients has changed since the introduction of Bortezomib. Despite therapeutic advances, HDT remains the treatment of choice for eligible patients. Standard prognosis systems (i.e., ISS and DS), cytogenetic or GEP have been mainly evaluated before new active drugs. Current data suggest that novel agents can overcome adverse prognostic factors, i.e., deletion 13q and t(4;14) at diagnosis.

Using our patient's database, we analyzed standard prognostic factors and transplant modalities on PFS and OS for 306 consecutive MM patients undergoing HDT from 1997 to 2009. 83 patients received Bortezomib + Dexamethasone and 223, VAD as induction regimen. When patients underwent tandem HDT (n=84), we considered only the first HDT. According to the induction therapy, we evaluated the influence of age, sex, isotype, DS and ISS staging systems, status before and post HDT, number of lines of therapy, time of HDT from diagnosis, dose of re-infused CD34(+) cells, bone marrow plasma cell infiltration (BMPCP) and beta2-microglobulin (SB2M) at diagnosis on OS and PFS. Data processing was performed using SAS software packages version 9.2. PFS measured from the date of first PBSCT to the relapse (Kaplan-Meier product limit method), and OS, from diagnosis to death or last follow-up. The association of potential independent variables to PFS and OS was assessed by univariate analysis using Kaplan Meier method and Log Rank Test, then, by multivariate analysis through Cox proportional hazards model.

Median age was 61 years (34–73). Sex ratio M/F was 1.17. Fifty-four percent were IgG, 29%, IgA, 17%, light-chain. Median number of CD34 cells is 5.08 (1.2–26) x10⁶/Kg. Forty-five percent of patients had SB2M less than <3.5mg/L. Forty-eight percent had BMPCP ≥ 30%. Forty-one percent of patients were ISS I, 29%ISS II and 30 ISS III. Clinical DS staging was shared in 7% of stage 1, 18% of stage 2 and 75 % of stage 3 at diagnosis. Eighty-one% of PBSCT were preceded with one line of treatment before transplant. Ninety percent of patients have undergone one HDT and 80 % have received only one line of induction treatment. Median PFS follow-up was 45 months for VAD induction regimen (VIR) and 10 months for Bortezomib induction regimen (BIR). In VIR group, Isotype, SB2M, BMCP, sex, and post-transplant response are significant for PFS in univariate model. In Cox's model, BMPCP, sex, isotype, and post-transplant response are significant. In contrast, after BIR, only post-transplant response remains a significant prognosis factor (p<0.0001). Isotype (p=0.41), SB2M (p=0.62), BMCP (p=0.4), are not significant. Median OS follow-up was 57 months for VIR and 21 months for BIR. In VIR group BMPCP, post-transplant response, isotype, SB2M, age at transplant, and ISS were the most consistent prognosis factors correlated with OS. In Cox's model only BMCP, post-transplant response, isotype and ISS are significant. In the BIR group, only post-transplant response is a significant factor correlated with OS (p=0.05). ISS (p=0.73) nor SDD (p=0.89) are significant (Fig 1). However, there are few events in each category. Bortezomib modifies usual prognosis scoring system as ISS or SDD.