Lucie Brozova

Subcutaneous Bortezomib in Multiple Myeloma Patients Induces Similar Therapeutic Response Rates as Intravenous Application But It Does Not Reduce the Incidence of Peripheral Neuropathy

Objective Subcutaneous (SC) application of bortezomib has been recently introduced as a new application route in multiple myeloma (MM) patients. We performed an analysis to compare the outcomes of bortezomib-based therapy in multiple myeloma (MM) patients treated using either intravenous (IV) or subcutaneous (SC) route of administration. Patients and methods During January 2012 through December 2013, we performed a retrospective analysis of 446 patients with MM treated with bortezomib-based regimens (either once weekly – 63% or twice weekly – 27%) in both, the first line setting, and in relapse, with separate analysis of patients undergoing autologous stem cell transplantation. We assessed the response rates and toxicity profiles in both, IV and SC route of bortezomib administration. Results The response rates in both IV and SC arm were similar with overall response rate 71.7% vs 70.7%, complete remissions in 13.9% vs 8.6%, very good partial remissions in 30.8% vs 34.5% and partial remissions in 27% vs 27.6%. The most frequent grade ≥3 toxicities were anemia, thrombocytopenia and neutropenia, with no significant differences between IV and SC group. There were no significant differences in the rate of peripheral neuropathy (PN). PN of any grade was present in 48% in the IV arm and in 41% in the SC arm. PN grade ≥2 was present in 20% vs 18% and PN grade ≥3 was present in 6% vs 4%. Conclusions We conclude that subcutaneous application of bortezomib has similar therapeutic outcomes and toxicity profile as intravenous route of application. In our cohort there was no difference in the incidence of PN, suggesting that PN is dose dependent and might be reduced by lower intensity schemes rather than by the route of administration.

Anesthesia for Cesarean Delivery in the Czech Republic: A 2011 National Survey

BACKGROUND:The purpose of this national survey was to determine current anesthesia practices for cesarean delivery in the Czech Republic. METHODS:In November 2011, we invited all departments of obstetric anesthesia in the Czech Republic to participate in a prospective study to monitor consecutive peripartum obstetric anesthesia procedures. Data were recorded online in the TrialDB database (Yale University, New Haven, CT). RESULTS:The response rate was 51% (49 of 97 departments); participating centers represented 60% of all births in the country during the study period. There were 1943 cases of peripartum anesthesia care, of which 1166 cases (60%) were anesthesia for cesarean delivery. Estimates were weighted based on population distribution of cesarean delivery among types of participating centers. Neuraxial anesthesia was used in 55.6% (95% confidence interval [CI], 52.8%–58.5%); the distribution of anesthesia techniques differed among type of participating center. The rate of neuraxial anesthesia in university hospitals was 55.6% (95% CI, 51.5%–59.6%), 32.4% (95% CI, 26.4%–39.0%) in regional hospitals, and 60.7% (95% CI, 55.2%–66.0%) in local hospitals. The reasons for cesarean delivery under general anesthesia were emergency procedure (67%), refusal of neuraxial blockade by parturient (30%), failure of neuraxial anesthesia (6%), and preoperative administration of low-molecular-weight heparin (3%). Postcesarean analgesia was primarily provided by systemic opioid (66%) and nonopioid analgesics (61%), solely or in combination. Epidural postoperative analgesia was used in 14% of cases. Compared with national neuraxial anesthesia rate data published in the 1990s (6.7% in 1993), there has been an upward trend in the use of neuraxial anesthesia for cesarean delivery during the 21st century (40.5% in 2000) in the Czech Republic. CONCLUSIONS:The rate of neuraxial anesthesia use for cesarean delivery has increased in the Czech Republic in the last 2 decades. However, the current rate of general anesthesia is high compared with other Western countries.

IgM myeloma: A multicenter retrospective study of 134 patients

IgM myeloma is a rare hematologic malignancy for which the clinicopathological features and patient outcomes have not been extensively studied. We carried out a multicenter retrospective study in patients with diagnosis of IgM myeloma defined by >10% marrow involvement by monoclonal plasma cells, presence of an IgM monoclonal paraproteinemia of any size, and anemia, renal dysfunction, hypercalcemia, lytic lesions and/or t(11;14) identified by FISH. A total of 134 patients from 20 centers were included in this analysis. The median age at diagnosis was 65.5 years with a male predominance (68%). Anemia, renal dysfunction, elevated calcium and skeletal lytic lesions were found in 37, 43, 19, and 70%, respectively. The median serum IgM level was 2,895 mg dL−1 with 19% of patients presenting with levels >6,000 mg dL−1. International Staging System (ISS) stages 1, 2, and 3 were seen in 40 (33%), 54 (44%), and 29 (24%) of patients, respectively. The malignant cells expressed CD20 (58%) and cyclin D1 (67%), and t(11;14) was the most common cytogenetic finding (39%). The median overall survival (OS) was 61 months. Higher ISS score was associated with worse survival (P = 0.02). Patients with IgM myeloma present with similar characteristics and outcomes as patients with more common myeloma subtypes.

Circulating exosomal long noncoding RNA PRINS-First findings in monoclonal gammopathies.

Multiple myeloma is the second most common hematological malignancy characterized by focal lesions of malignant plasma cells in the bone marrow. These lesions contain subclones that directly influence survival of patients. Bone marrow biopsies are single‐site biopsies and thus cannot contain all information about the tumor. In contrast, liquid biopsies analyze circulating cells and molecules that are secreted from all sites of the tumor. Long noncoding RNA molecules are one class of these molecules. We performed a two‐phase biomarker study investigating lncRNA expression profiles in exosomes of peripheral blood serum of newly diagnosed multiple myeloma (MM) patients, monoclonal gammopathy of undetermined significance (MGUS) patients in comparison with healthy donors (HD). Surprisingly, this analysis revealed dysregulation of only one exosomal lncRNA PRINS in MM vs HD. Overall, MM and MGUS patients were distinguished from HD with sensitivity of 84.9% and specificity of 83.3%. Our study suggests a possible diagnostic role for exosomal lncRNA PRINS in monoclonal gammopathies patients.