Foran, James M.

BACKGROUNDNational Cancer Institute (NCI)/National Comprehensive Cancer Network (NCCN)–designated cancer centers (CCs) offer patients state‐of‐the‐art treatment, but their impact on multiple myeloma (MM) patient outcomes has not been evaluated.METHODSAdult MM patients diagnosed between 1973 and 2011 were identified from the Surveillance, Epidemiology, and End Results database and were stratified by the county of residence at the time of diagnosis and the year of CC designation. The influence of NCI/NCCN CC access, race, and the year of diagnosis on overall survival (OS) was evaluated with a Cox regression model.RESULTSA statistically significant OS improvement was noted in patients diagnosed after 1995 with access to 2 or more NCI CCs overall (P = .002 for 1996‐2002; P < .001 for 2003‐2011) and by race for whites (hazard ratio [HR] for 1996‐2002, 0.85; 95% confidence interval [CI], 0.78‐0.91; HR for 2003‐2011, 0.85; 95% CI, 0.79‐0.91) but not for nonwhites. For NCCN access, improvement was seen in 1996‐2002 (P = .003), in 2003‐2011 (P < .001), and by race for whites (HR, 0.917; 95% CI, 0.88‐0.95) and nonwhites (0.94; 95% CI, 0.89‐0.99), but within nonwhites, this was true only for African Americans (AAs; HR, 0.88; 95% CI, 0.81‐0.97) and not for Asians, Hispanics, or Native Americans.CONCLUSIONSImprovement in OS was seen in MM patients diagnosed after 1995 with access to 1 NCCN CC or 2 or more NCI CCs. NCI access benefited only whites, whereas NCCN access benefited only white and AA patients. No OS benefit was seen for any subgroup with access to only 1 NCI center. Eliminating racial disparities in health care access and utilization is needed to improve outcomes. Cancer 2016;122:618–625. © 2015 American Cancer Society.

It is important to separate socioeconomic factors affecting health care quality from confounders related to patients’ baseline status or disease biology when studying disparities in lymphoma survival.

Purpose Lenalidomide has significant single-agent activity in relapsed diffuse large B-cell lymphoma (DLBCL). We demonstrated that lenalidomide can be safely combined with R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone); this new combination is known as R2CHOP. The goal of this phase II study was to evaluate the efficacy of this combination in newly diagnosed DLBCL. Patients and Methods Eligible patients were adults with newly diagnosed untreated stages II to IV CD20 + DLBCL. Patients received lenalidomide 25 mg orally per day on days 1 through 10 with standard-dose R-CHOP every 21 days for six cycles. All patients received pegfilgrastim on day 2 of each cycle and aspirin prophylaxis throughout. DLBCL molecular subtype was determined by tumor immunohistochemistry and classified as germinal center B-cell (GCB) versus non-GCB in the R2CHOP patients and 87 control patients with DLBCL from the Lymphoma Database who were treated with conventional R-CHOP. Results In all, 64 patients with DLBCL were enrolled, and 60 were evaluable for response. The overall response rate was 98% (59 of 60) with 80% (48 of 60) achieving complete response. Event-free survival and overall survival (OS) rates at 24 months were 59% (95% CI, 48% to 74%) and 78% (95% CI, 68% to 90%), respectively. In R-CHOP patients, 24-month progression-free survival (PFS) and OS were 28% versus 64% (P < .001) and 46% versus 78% (P < .001) in non-GCB DLBCL versus GCB DLBCL, respectively. In contrast, there was no difference in 24-month PFS or OS for R2CHOP patients on the basis of non-GCB and GCB subtype (60% v 59% [P = .83] and 83% v 75% [P = .61] at 2 years, respectively). Conclusion R2CHOP shows promising efficacy in DLBCL. The addition of lenalidomide appears to mitigate a negative impact of non-GCB phenotype on patient outcome.

Key Points Patients living in low SES neighborhoods had worse survival after DLBCL. Disparity was most striking in younger (non-Medicare) patients and after the introduction of rituximab.

SummaryMultiple myeloma, the second most common haematological malignancy in the U.S., is currently incurable. Disruption of the intrinsic apoptotic pathway by BCL2 and MCL1 upregulation is observed in >80% of myeloma cases and is associated with an aggressive clinical course. Remarkably, there is no approved drug with the ability to target BCL2 or MCL1. Thus, we investigated the anti‐tumour effects of a pan‐BCL2 inhibitor, AT‐101, which has high binding specificity for BCL2 and MCL1 in preclinical models of plasma cell cancers (Multiple myeloma and Waldenström macroglobulinaemia). Gene expression and immunoblot analysis of six plasma cell cancer models showed upregulation of BCL2 family members. AT‐101 was able to downregulate BCL2 and MCL1 in all plasma cell cancer models and induced apoptotic cell death in a caspase‐dependent manner by altering mitochondrial membrane permeability. This cytotoxic effect and BCL2 downregulation were further potentiated when AT‐101 was combined with lenalidomide/dexamethasone (LDA). NanoString nCounter mRNA quantification and Ingenuity Pathways Analysis revealed differential changes in the CCNA2, FRZB, FYN, IRF1, PTPN11 genes in LDA‐treated cells. In summary, we describe for the first time the cellular and molecular events associated with the use of AT‐101 in combination with lenalidomide/dexamethasone in preclinical models of plasma cell malignancy.