Real-world effectiveness and safety analysis of carfilzomib-lenalidomide-dexamethasone and carfilzomib-dexamethasone in relapsed/refractory multiple myeloma: a multicenter retrospective analysis

Background: Little is known about the real-world survival benefits and safety profiles of carfilzomib-lenalidomide-dexamethasone (KRd) and carfilzomib-dexamethasone (Kd). Methods: We performed a retrospective analysis to evaluate their efficacy and safety in 157 patients registered in the Kansai Myeloma Forum database. Results: A total of 107 patients received KRd. Before KRd, 99% of patients had received bortezomib (54% were refractory disease), and 82% had received lenalidomide (57% were refractory disease). The overall response rate (ORR) was 68.2%. The median progression-free survival (PFS) and overall survival (OS) were 8.8 and 29.3 months, respectively. Multivariate analysis showed that reduction of the carfilzomib dose and non-IgG M protein were significantly associated with lower PFS and reduction of the carfilzomib dose and refractoriness to prior bortezomib-based regimens were significantly associated with lower OS. A total of 50 patients received Kd. Before Kd, 96% of patients had received bortezomib (54% were refractory disease). The ORR was 62.0%. The median PFS and OS were 7.1 and 20.9 months, respectively. Based on the multivariate analysis, reduction of the carfilzomib dose and International Staging System Stage III (ISS III) were significantly associated with lower PFS. Grade III or higher adverse events were observed in 48% of KRd cases and 54% of Kd cases. Cardiovascular events, cytopenia, and infections were frequent, and 4 KRd patients died due to heart failure, arrhythmia, cerebral hemorrhage, and pneumonia. Conclusion: Our analysis showed that an adequate dose of carfilzomib is important for achieving the best survival benefits in a real-world setting. Adverse effects after KRd and Kd therapy should also be considered

Bone morphogenetic protein 7 in dormancy and metastasis of prostate cancer stem-like cells in bone

BMP7 released by bone marrow stromal cells induces reversible senescence of prostate cancer stem-like cells, and BMPR2 expression inversely correlates with bone metastasis and recurrence in prostate cancer patients

Insects from the grazing food web favoured the evolutionary habitat shift to bright environments in araneoid spiders

The Araneoidea comprises a diverse group of web-building spiders, and part of this diversity is believed attributable to habitat expansion to bright environments. We clarified the fitness-related advantages of living in such environments by examining prey availability and the growth rates of 10 species in three families inhabiting grassland (bright) and forest understory (dim) habitats. Spiders in the grassland habitat captured more prey, derived mainly from the grazing food web, than those in the forest-floor environment, and this difference was manifested in their growth rate. Independent contrasts indicated that increased utilization of insects from the grazing food web led to an evolutionary increase in adult body size. These results suggest that the shift to bright environments enabled araneoid spiders to evolve diverse life-history traits, including rapid growth and large size, which were not possible in dim environments

Response to human-modified landscape of an apex consumer: Sex- and season-related variations in road selection and movement pattern

The recovery of apex consumers increases the need for coexistence efforts, and it is important to understand how apex consumers respond to human-modified landscapes. Roads can restrict movement and gene flow as well as increase mortality risk, however, can also provide attractive food resources along roadside and enhance movement efficiency of apex consumer. To investigate the selectivity (preference/avoidance) and movement patterns of an apex consumer in relation to roads, we carried out an integrated step selection analysis of GPS data from Asiatic black bears (Ursus thibetanus) in the Ashio-Nikko Mountains, Japan. During the reproductive season, adult males preferred areas near all types of roads, but preferred areas further from roads during the day compared to the night. Also, adult males displayed slower movements as well as avoided less dense vegetation near main roads and faster movement near minor roads. In comparison, adult females avoided areas near main roads and preferred areas near minor roads. In addition, adult females preferred areas further from minor roads during the day compared to the night. In the hyperphagia season, neither sex exhibited any selectivity in relation to roads in general, but preferred areas farther from all types of roads during the day. Our results suggest that Asiatic black bears not only generally perceive roads as a risk but also may use areas near roads for food resources or travel routes depending on sex, season, and human activity level. To minimize bear-human encounters near roads, we propose that management of roadside vegetation focuses on creating habitats with high visibility and plant species unattractive for bears

Significance of maintenance therapy after HDT/ASCT in symptomatic multiple myeloma: A multicenter retrospective analysis in Kansai Myeloma Forum

Abstract A total of 129 symptomatic patients with multiple myeloma (MM) who underwent high‐dose chemotherapy with autologous stem cell transplantation (HDT/ASCT) were analyzed. The 4‐year overall survival (OS) of patients with maintenance (n = 82) was 80%, whereas that of patients without maintenance (n = 47) was 72% (p = 0.426). The 4‐year progression‐free survival (PFS) of patients with maintenance was 38%, whereas that of patients without maintenance was 27% (p = 0.088). Multivariate analysis revealed that an International Staging System score ≥2 was associated with worse PFS (hazard ratio 1.62, p = 0.043). Among the 129 patients, two were excluded owing to early relapse, 50 patients achieved complete response (CR), and 77 patients failed to achieve CR. Patients who achieved CR showed better 4‐year PFS than those who failed to achieve CR (41% vs. 30%, p = 0.027); however, 4‐year OS was not different (76% vs. 82%, p = 0.971). In patients who achieved CR, 4‐year OS with/without maintenance was 74%/81% (p = 0.357), 4‐year PFS with/without maintenance was 42%/40% (p = 0.954). In patients who failed to achieve CR, the 4‐year OS with/without maintenance was 97%/91% (p = 0.107), and 4‐year PFS with/without maintenance was 36%/16% (p < 0.001). In patients who failed to achieve CR, maintenance significantly improved the PFS. Maintenance after HDT/ASCT can prolong PFS in patients who fail to achieve CR in real‐world settings

Retrospective analysis of primary plasma cell leukemia in Kansai Myeloma Forum registry

We retrospectively analyzed twenty-six patients with primary plasma cell leukemia (pPCL) registered from May 2005 until April 2015 by the Kansai Myeloma Forum. Twenty patients received novel agents (bortezomib or lenalidomide), and their median survival of was 34 months. The median survival of patients who underwent autologous stem cell transplantation (SCT) was 40 months, those undergoing allogeneic SCT 55 months, and those undergoing both types of SCT (auto–allo) 61 months; whereas for those who did not undergo SCT it was 28 months (p = 0.845). The only statistically significant risk factor identified by multivariate analysis was hypercalcemia. Keywords: Primary plasma cell leukemia, Novel agent, Hypercalcemia, Stem cell transplantatio