Singh, Preet Paul

AbstractExperience with intensive chemotherapy for relapsed/refractory multiple myeloma (RRMM) using VDT PACE regimen and its modifications (VDT PACE‐like regimens: VPLRs) outside TOTAL THERAPY trials is limited. We analyzed the outcomes of 141 patients with RRMM who received VPLRs at our center between 2006 and 2017 in an intent‐to‐treat analysis. Median age was 59.7 years and 66.7% of patients were male. A median of 2.2 years (range 0.02‐11.4) separated diagnosis of myeloma and inititation of VPLR. High‐risk cytogenetics were present in 52.4% patients. Patients received a median of 4 (range 1‐14) prior therapies, including stem cell transplant (SCT) in 66.7% patients. Ninety‐five (67.4%) patients received VDT PACE, 20 (14.2%) patients received VD PACE and 26 (18.4%) patients received other VPLRs. Patients received a median of 1 cycle (range 1‐9) of VPLR. We observed ≥ minimal response in 68.4%, ≥ partial response (PR) in 54.4% and ≥ very good PR in 10.3% patients. Median progression‐free survival was 3.1 months (95% CI, 1.9‐3.9) and median overall survival (OS) was 8.1 months (CI, 6.2‐9.9). One‐hundred and sixteen (82.3%) patients received some therapy after VPLR; 71 (61.2%) received systemic chemotherapy, while 45 (38.8%) underwent SCT. Median OS for those who received SCT after VPLR was 15.1 months (CI, 10.3‐20.8). Age ≥ 60 years (hazard ratio [HR] 2.3 [CI, 1.4‐3.7]; P = 0.0008) and R‐ISS III stage (HR‐ 2.4 [CI, 1.3‐4.0]; P = 0.003) predicted shorter OS in patients receiving VPLR. VPLRs are effective in heavily pre‐treated RRMM. In fit patients, SCT can be used to consolidate the response to VPLR.

522 Background: Metformin inhibits mTOR and downstream pathways involved in cell proliferation and survival by inducing AMPK activation. Although its use has been associated with decreased risk of colorectal cancer (CRC), the effect of metformin on cancer related mortality is unclear. We performed a meta-analysis of published observational studies evaluating metformin use in patients with CRC and its association with overall and CRC-specific survival. Methods: Through a systematic search of PubMed and conference presentations (cut-off: August 2013), we identified 8 observational studies (18,537 total patients with CRC; 6242 CRC patients with DM) reporting the association between metformin use and survival after diagnosis of CRC. Summary hazard ratio (HR) with 95% confidence intervals (CI) was estimated using the random effects model, and heterogeneity was measured using the inconsistency index (I2). Results: On meta-analysis, metformin use was associated with a 34% reduction in mortality in CRC patients as compared to non-use (adjusted HR, 0.66; 95% CI, 0.54-0.81), albeit with high heterogeneity (I2=66.9%). After exclusion of one study, which contributed to considerable heterogeneity, a 28% reduction in mortality was considered a more conservative, consistent effect estimate (adjusted HR, 0.72; 95% CI, 0.64-0.81), with minimal heterogeneity (I2=16.2%). On restricting analysis only to patients with DM, use of metformin (vs non-use) was associated with decreased all-cause mortality (6 studies; adjusted HR, 0.63; 95% CI, 0.49-0.81) and CRC-specific mortality (3 studies; adjusted HR, 0.66; 95% CI, 0.50-0.87). Conclusions: Based on meta-analysis of observational studies, the use of metformin in diabetic patients with CRC appears to be associated with reduced all-cause mortality and CRC-specific mortality. Further prospective investigation of metformin’s effect on outcome in CRC patients is warranted.

11 Background: Acid-suppressive medications, particularly proton pump inhibitors (PPI), may modify risk of esophageal adenocarcinoma (EAC) in patients with Barrett’s esophagus (BE). We performed a systematic review and meta-analysis of studies evaluating the association between PPIs and histamine receptor antagonists (H2RA) and risk of EAC or high-grade dysplasia (BE-HGD) in patients with BE. Methods: Through a systematic search up to June 2013, we identified 7 observational studies (5 cohort studies and 2 case-control studies; 2,813 patients with BE, 317 cases of EAC and/or BE-HGD, 84.4% PPI users) reporting the association between PPIs or H2RA and EAC in patients with BE. Summary odds ratio (OR) with 95% confidence intervals (CI) was estimated using random effects model, and heterogeneity was measured using the inconsistency index (I2). Results: On meta-analysis, PPI use was associated with 71% reduction in EAC risk in patients with BE (adjusted OR, 0.29; 95% CI, 0.12-0.71). There was a trend toward a dose-response relationship with PPI use for >2 years protective against EAC [3 studies; PPI use >2 years vs. <2 years (as compared to no use): OR, 0.45 (0.19-1.06) vs. 1.09 (0.47-2.56)]. Considerable heterogeneity was observed in the overall analysis (I2=81%). On restricting analysis to 5 cohort studies, use of PPIs was consistently associated with a lower risk of EAC and/or BE-HGD (adjusted OR, 0.33; 95% CI, 0.19-0.58; I2=9%). H2RA use was not associated with decreased risk of EAC in patients with BE based on 2 studies (adjusted OR, 1.15; 95% CI, 0.77-1.72). Using a 67% summary risk reduction (derived from cohort studies) of EAC and/or BE-HGD with PPI use in patients with BE, and observed cumulative incidence rates of EAC and/or BE-HGD in patients with BE overall as 10.2 per 1,000 patient years, we estimate the number needed to treat with PPIs to prevent 1 case of EAC or BE-HGD in BE patients at 147. Conclusions: Based on meta-analysis of observational studies, the use of PPI, but not H2RA appears to be associated with a decreased risk of EAC and/or BE-HGD in patients with BE. PPI use should be considered in BE, and chemopreventive trials of PPIs in patients with BE are warranted.

686 Background: Preclinical evidence suggests that statins have anti-neoplastic properties by inhibiting cell proliferation, and inducing apoptosis. Statins may be associated with reduced risk of colorectal cancer (CRC), but their effect on CRC related mortality is unclear. We performed a meta-analysis of published observational studies evaluating statin use in patients with CRC and its association with overall and CRC-specific mortality. Methods: Through a systematic search upto August 2014, we identified 7 observational studies (64,773 patients with CRC;19.5% statin users) reporting the association between statin use and mortality in patients with CRC. Summary hazard ratio (HR) with 95% confidence intervals (CI) was estimated using the random effects model, and heterogeneity was measured using the inconsistency index (I2). Results: On meta-analysis, statin use was associated with a 26% reduction in all-cause mortality in CRC patients as compared to non-use (6 studies; adjusted HR, 0.74; 95% CI, 0.67-0.83) with minimal heterogeneity (I2=18%), after adjusting for age, sex and CRC stage. Only one study adjusted for concomitant metformin use. Five studies evaluated CRC-specific mortality; on meta-analysis, use of statins (vs non-use) was also associated with decreased CRC-specific mortality (adjusted HR, 0.74; 95% CI, 0.70-0.83; minimal heterogeneity, I2=17%). On limiting analysis to statin use after diagnosis of CRC, use of statins remained significantly associated with reduced CRC-specific mortality (3 studies; adjusted HR, 0.70; 95% CI, 0.60-0.81), but not overall mortality (4 studies; adjusted HR, 0.82; 95% CI, 0.64-1.05). On restricting analysis to studies, which adjusted for concomitant use of aspirin/NSAID, the inverse association between statin use and overall- (5 studies; adjusted HR, 0.74; 95% CI, 0.66-0.84) and CRC-specific mortality (4 studies; adjusted HR, 0.76; 95% CI, 0.69-0.84) remained significant. Conclusions: Based on this meta-analysis, statin use in patients with CRC may be associated with reduced all-cause and CRC-specific mortality. This observation merits prospective investigation of statins’ effect on outcome in CRC patients.