Tumor-specific mutations can result in immunogenic neoantigens, both of which have been correlated with responsiveness to immune checkpoint inhibitors in highly mutagenic cancers. However, early results of single-agent checkpoint inhibitors in multiple myeloma (MM) have been underwhelming. Therefore, we sought to understand the relationship between mutation and neoantigen landscape of MM patients and responsiveness to therapies. Somatic mutation burden, neoantigen load, and response to therapy were determined using interim data from the MMRF CoMMpass study (NCT01454297) on 664 MM patients. In this population, the mean somatic and missense mutation loads were 405.84(s=608.55) and 63.90(s=95.88) mutations per patient, respectively. There was a positive linear relationship between mutation and neoantigen burdens (R2=0.862). The average predicted neoantigen load was 23.52(s=52.14) neoantigens with an average of 9.40(s=26.97) expressed neoantigens. Survival analysis revealed significantly shorter progression-free survival (PFS) in patients with greater than average somatic missense mutation load (N=163, 0.493 vs 0.726 2-year PFS, P=0.0023) and predicted expressed neoantigen load (N=214, 0.555 vs 0.729 2-year PFS, P=0.0028). This pattern is maintained when stratified by disease stage and cytogenetic abnormalities. Therefore, high mutation and neoantigen load are clinically relevant risk factors that negatively impact survival of MM patients under current standards of care.

Although the incidence of Bordetella pertussis infections had decreased significantly since the introduction of widespread vaccination, an increase in the number of cases has occurred recently. In an attempt to define the seroepidemiology of pertussis in Nashville, antibody levels to pertussis toxin (PT) and filamentous hemagglutinin (FHA) were measured by ELISA in 585 serum samples from healthy 1- to 65-year-old subjects. Data were analyzed by smooth curve fitting and by comparison of trends in PT and FHA titers across age groups. The results demonstrated a peak in PT and FHA titers in the 4-6 year age group, concurrent with the administration of booster doses of diphtheria-tetanus toxoid-pertussis vaccine. A second larger peak was noted in the 13-17 year age group. These data suggest that pertussis infection is frequent during the adolescent years.

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Breast cancer in women is a major health problem, causing a great deal of suffering and a high number of deaths. So far, early diagnosis followed by surgery is the only way to cure the disease, while therapeutic protocols for women at an advanced stage of the disease are still unsatisfactory and, in the long term, metastatic breast cancer is still associated with high treatment failure. 1 In humans, both chemotherapy and hormonal approaches for the management of the advanced disease are of great clinical relevance. Various drugs, including taxol, are active against disseminated breast cancer. 2 In addition, in patients with estrogen receptor positive tumors, antiestrogens, and tamoxifen in particular, have been widely used. 3 Many randomized trials have shown that postsurgical tamoxifen (TAM) treatment significantly reduces the growth of hormone receptor-positive breast cancer. Recently, the efficacy of TAM for chemoprevention of breast tumors has been evaluated, and the data from the Breast Cancer Prevention Trial have demonstrated that TAM administration reduces the incidence of estrogen receptor-positive, but not receptor-negative tumors. 4,5 More recently, inhibition of tumor angiogenesis was investigated as a therapeutic strategy that can inhibit Correspondence: MG Sacco, CNR-ITB, Via Fratelli Cervi, 93, 20090 Segrate (MI)