Bendamustine and rituximab as induction therapy in both transplant-eligible and -ineligible patients with mantle cell lymphoma.

Rituximab-containing chemotherapy regimens constitute standard first-line therapy for mantle cell lymphoma (MCL). Since June 2013, 190 patients ≥18 years of age with MCL in British Columbia have been treated with bendamustine and rituximab (BR). The overall response rate to BR was 88% (54% complete response). Of these, 61 of 89 patients (69%) aged ≤65 years received autologous stem cell transplantation and 141 of 190 patients (74%) from the entire cohort received maintenance rituximab. Twenty-three patients (12%) had progressive disease, associated with high risk per the Mantle Cell Lymphoma International Prognostic Index (MIPI), Ki-67 ≥50%, and blastoid/pleomorphic histology. Outcomes were compared with a historical cohort of 248 patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP; January 2003 to May 2013). Treatment with BR was associated with significant improvements in progression-free survival (PFS), but not overall survival (OS), compared with R-CHOP in the whole cohort (3-year PFS, 66% BR vs 51% R-CHOP, P = .003; 3-year OS, 73% BR vs 66% R-CHOP, P = .054) and in those >65 years of age (3-year PFS, 56% BR vs 35% R-CHOP, P = .001; 3-year OS, 64% BR vs 55% R-CHOP, P = .063). Outcomes in transplanted patients were not statistically significantly different compared with R-CHOP (3-year PFS, 85% BR vs 76% R-CHOP, P = .135; 3-year OS, 90% BR vs 88% R-CHOP, P = .305), although in multivariate analyses, treatment with BR was associated with improved PFS (hazard ratio, 0.40 [95% confidence interval, 0.17-0.94]; P = .036) but not OS. BR is an effective first-line option for most patients with MCL, however, outcomes are suboptimal for those with high-risk features and further studies integrating novel agents are warranted.

Homologous Recombination Deficiency in Breast Cancer: A Clinical Review.

BRCA1 and BRCA2 germline mutation-associated breast cancers are known to be deficient in the process of homologous recombination and often respond favorably to drugs targeting this important DNA repair pathway. There is emerging evidence that a significant proportion of patients with BRCA1/BRCA2 wild-type breast cancer are also deficient in homologous recombination, and it is hypothesized that these patients may derive similar benefit from drugs targeting this pathway. Current research has focused on the development of a companion diagnostic to identify these sporadic BRCA-like tumors. This review outlines the various approaches that researchers have taken to predict homologous recombination deficiency as part of correlative biomarker work in various studies and clinical trials in breast cancer. As some of these tests of homologous recombination deficiency move closer to clinical use, understanding the approach and limitations of each is of relevance to clinicians who treat patients with breast cancer.

Survival with metastatic breast cancer based on initial presentation, de novo versus relapsed.

PURPOSE: We hypothesized different Overall Survival (OS) in metastatic breast cancer (MBC) after relapse vs de novo presentation. METHODS: We identified women in British Columbia with MBC diagnosed between 01/2001 and 12/2009. OS from MBC was calculated for relapsed vs de novo cohorts in 3 subgroups, based on hormone receptors (HR) and HER2 status. Age at MBC, disease-free interval (DFI), de novo vs relapsed, year of MBC diagnosis, and systemic treatment were entered into univariable and multivariable analyses. RESULTS: We identified 3645 pts with known HR of which 2796 had known HER2. Median follow-up was 91 months. Median OS was longer for de novo vs relapsed MBC: HR+/HER2- 34 versus 23 months (mos) (p < 0.0001), HR-/HER2- (TN) 11 versus 8 mos (p = 0.02), HER2+ 29 versus 15 mos (p < 0.0001). For TN disease, no variable independently discriminated a group with increased risk of death. For both the HR +/HER2- and the HER2 + groups, relapsed vs de novo status (HzR 1.4 [95% CI 1.2-1.5; p < 0.0001], and HzR 1.6 [95% CI 1.4-1.9; p < 0.0001], respectively) and age >50 (HzR 1.2 [95% CI 1.1-1.4; p = 0.001] and HzR 1.3 [95% CI 1.1-1.5; p = 0.01], respectively) were associated with increased risk of death on multivariable analysis. CONCLUSION: These data provide information that may guide discussions about prognosis between physicians and patients with MBC. In addition, it highlights the importance of stratifying for initial stage at diagnosis in future MBC therapeutic trials.