PracticeUpdate: Oncology - Winter 2018

EDITOR’S PICKS 17

Risk Stratification of Smoldering Multiple Myeloma Incorporating Revised IMWG Diagnostic Criteria Blood Cancer Journal Take-home message • This study identified 421 patients with smoldering multiple myeloma (SMM). The median time to progression (TTP) was 57 months. Data indicated BMPC% >20%, M-protein >2 g/ dL, and FLCr >20 independently predicted shorter TTP in multivariate analysis. Patients were then stratified into three groups: low risk (none of the three risk factors; n=143); inter- mediate risk (one of the three risk factors; n=121); and high risk (at least two of the three risk factors; n=153). The median TTP for low-, intermediate-, and high-risk groups were 110, 68, and 29 months, respectively (P < .0001). • The study authors concluded that BMPC%>20%, M-pro- tein >2 g/dL, and FLCr >20 at diagnosis can be used to risk-stratify patients with SMM. Patients with high-risk SMM need close follow-up and are candidates for clinical trials aiming to prevent progression. Jeffrey Wiisanen MD " BMPC%>20%, M-protein>2g/dL, and FLCr>20 at diagnosis can be used to risk-stratify patients with SMM. Patients with high-risk SMMneed close follow-up and are candidates for clinical trials aiming to prevent progression. " Abstract In 2014, the International Myeloma Working Group reclassified patients with smoldering multiple myeloma (SMM) and bone marrow-plasma cell percentage (BMPC%) ≥ 60%, or serum free light chain ratio (FLCr) ≥ 100 or >1 focal lesion on magnetic resonance imaging as multiple myeloma (MM). Predictors of progression in patients currently classified as SMM are not known. We identified 421 patients with SMM, diagnosed between 2003 and 2015. The median time to progression (TTP) was 57 months (CI, 45-72). BMPC% >20% [hazard ratio (HR): 2.28 (CI, 1.63-3.20); p<0.0001]; M-protein > 2g/dL [HR: 1.56 (CI, 1.11-2.20); p = 0.01], and FLCr > 20 [HR: 2.13 (CI, 1.55-2.93); p < 0.0001] independently predicted shorter TTP in multivariate analysis. Age and immunoparesis were not significant. We stratified patients into three groups: low risk (none of the three risk factors; n= 143); intermediate risk (one of the three risk factors; n= 121); and high risk (≥2 of the three risk factors; n= 153). The median TTP for low-, inter- mediate-, and high-risk groups were 110, 68, and 29 months, respectively (p<0.0001). BMPC%>20%, M-protein >2g/dL, and FLCr >20 at diagno- sis can be used to risk stratify patients with SMM. Patients with high-risk SMM need close follow-up and are candidates for clinical trials aiming to prevent progression. Risk Stratification of Smoldering Multiple Myeloma Incorporating Revised IMWG Diagnostic Criteria. Blood Cancer J 2018 Jun 12;8(6)59, A Laksh- man, SV Rajkumar, FK Buadi, et al. www.practiceupdate.com/c/69662

Patients were monitored for tumor recurrence, progression to mus- cle invasion, survival, and toxic effects. The final date of follow-up was August 14, 2016. INTERVENTIONS Participants were randomly assigned to receive intra- vesical instillation of gemcitabine (2 g in 100 mL of saline) (n =201) or saline (100 mL) (n=205) for 1 hour immediately following TURBT. MAINOUTCOMES ANDMEASURES The primary outcome was time to recur- rence of cancer. Secondary end points were time to muscle invasion and death due to any cause. RESULTS Among 406 randomized eligible patients (median age, 66 years; 84.7% men), 383 completed the trial. In the intention-to-treat analysis, 67 of 201 patients (4-year estimate, 35%) in the gemcitabine group and 91 of 205 patients (4-year estimate, 47%) in the saline group had cancer recurrence within 4.0 years (hazard ratio, 0.66; 95% CI, 0.48-0.90; P<.001 by 1-sided log-rank test for time to recur- rence). Among the 215 patients with low-grade non–muscle-invasive urothelial cancer who underwent TURBT and drug instillation, 34 of 102 patients (4-year estimate, 34%) in the gemcitabine group and 59 of 113 patients (4-year estimate, 54%) in the saline group had cancer recurrence (hazard ratio, 0.53; 95% CI, 0.35-0.81; P= .001 by 1-sided log-rank test for time to recurrence). Fifteen patients had tumors that progressed to muscle invasion (5 in the gemcitabine group and 10 in the saline group; P= .22 by 1-sided log-rank test) and 42 died of any cause (17 in the gemcitabine group and 25 in the saline group; P= .12 by 1-sided log-rank test). There were no grade 4 or 5 adverse events and no significant differences in adverse events of grade 3 or lower. CONCLUSIONS AND RELEVANCE Among patients with suspected low- grade non–muscle-invasive urothelial cancer, immediate postresection intravesical instillation of gemcitabine, compared with instillation of saline, significantly reduced the risk of recurrence over a median of 4.0 years. These findings support using this therapy, but further research is needed to compare gemcitabine with other intravesical agents. Effect of Intravesical Instillation of Gemcitabine vs Saline Immediately Following Resection of Suspected Low-Grade Non-Muscle-Invasive Bladder Cancer on Tumor Recurrence: SWOG S0337 Randomized Clinical Trial. JAMA 2018 May 08;[EPub Ahead of Print], EM Messing, CM Tangen, SP Lerner. www.practiceupdate.com/c/67853

VOL. 2 • NO. 3 • 2018