Lenalidomide is clinically active in patients with relapsed or refractory B-CLL. These findings are encouraging and warrant further investigation of this agent in the treatment of this disorder.

No abstract

Age standardized incidence rates of breast cancer in developed countries is nearly threefold higher than in developing countries. Iran has had one of the lowest incidence rates for breast cancer in the world, but during the last four decades increasing incidence rates of breast cancer made it the most prevalent cancer in Iranian women. After adjustment for age, Iranian young women are at relatively higher risk of breast cancer than their counterparts in developed countries. The purpose of this study was to investigate some established risk factors of breast cancer in Iranian young women. A hospital‐based case control study comprising 521 women with histologically confirmed, incident breast cancer and 521 controls frequency‐matched by age and province of residence was conducted. Logistic regression performed to investigate associations of reproductive and anthropometric factors with breast cancer risk. In multivariate analysis, family history [odds ratio (OR): 1.61; 95% confidence interval (CI): 1.07–2.42], oral contraceptives (OC) usage (OR: 1.52; 95% CI: 1.11–2.08), low parity (OR parity ≥ 3 vs. 1–2: 0.33; 95% CI: 0.23–0.49), employment (OR: 1.83; 95% CI: 1.05–3.23) and shorter period of breast feeding (OR ≥ 37 months vs. < 37: 0.61; 95% CI: 0.44–0.84) were related to a higher risk of breast cancer in young women. This was the first study focusing on risk factors of breast cancer in Iranian young women. The trend of decreasing parity and shortened duration of breast feeding along with OC usage might partly explain the rapid rising of breast cancer incidence in Iranian young women.

Patients with chronic lymphocytic lymphoma (CLL) with high-risk cytogenetics [del(11q)(q22.3) or del(17p)(p13.1)] have limited therapeutic options and their prognosis remains poor. This analysis was conducted to determine the clinical activity of lenalidomide in patients with high-risk disease. Relapsed/refractory patients with CLL enrolled in a phase II clinical trial who had del(11q)(q22.3) or del(17p)(p13.1) were included in this analysis. Patients received single agent lenalidomide for 21 days of the 4 week treatment cycle. The overall response rate among patients with high-risk cytogenetics was 38%, with 19% of patients achieving a complete response. Median progression-free survival was 12.1 months, which is higher than demonstrated with other agents in comparable patient populations. In addition, the estimated 2-year survival probability was 58%, demonstrating that the responses achieved with lenalidomide are durable, even in patients with CLL with high-risk disease with poor risk cytogenetics.

No abstract

Summary Multiple 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.

No abstract

Summary Extramedullary plasma cell cancers, such as plasma cell leukemia (PCL) and multiple extramedullary plasmacytomas (MEP) are very aggressive malignancies. These can be primary (de-novo) or secondary due to progressive prior multiple myeloma (MM). Recent reports suggest an increase in incidence of these disorders. Compared to MM, organ invasion is common in PCL, while soft tissue tumors involving the head, neck or paraspinal area are common sites for MEP. Markers of poor prognosis are frequently observed in these extramedullary forms of plasma cell cancers, and survival is significantly inferior compared to patients with MM. Conventional chemotherapeutic and radiotherapy approaches have been employed with variable results. Even high dose chemotherapy with autologous stem cell rescue has not been able to demonstrate consistent improvement in survival outcome. Although not specifically evaluated, novel anti-plasma cell agents, such as the proteasome inhibitor bortezomib, and immunomodulatory drugs, such as lenalidomide, appear to be active against these aggressive cancers. Clinical and translational research directed at improved understanding of disease biology and development of novel therapeutics is urgently needed.