Chimeric Antigen Receptor T-Cell Therapy For Multiple Myeloma: A Consensus Statement From The European Myeloma Network

Adoptive cellular therapy using chimeric antigen receptor T-cell (CART) therapy is currently being evaluated in patients with relapsed / refractory multiple myeloma (MM). The majority of CAR-T cell programs now being tested in clinical trials are targeting B-cell maturation antigen. Several recent phase I / II trials show promising preliminary results in patients with MM progressing on proteasome inhibitors, immunomodulatory drugs and monoclonal antibodies targeting CD38. CAR-T cell therapy is a potentially life-threatening strategy that can only be administered in experienced centers. For the moment, CAR-T cell therapy for MM is still experimental, but once this strategy has been approved in relapsed/refractory MM, it will become one of the most important indications for this therapy in Europe and world-wide. This manuscript proposes practical considerations for the use of CAR-T cell therapy in MM, and discusses several important issues for its future development

Ethnicity and Population Structure in Personal Naming Networks

Personal naming practices exist in all human groups and are far from random. Rather, they continue to reflect social norms and ethno-cultural customs that have developed over generations. As a consequence, contemporary name frequency distributions retain distinct geographic, social and ethno-cultural patterning that can be exploited to understand population structure in human biology, public health and social science. Previous attempts to detect and delineate such structure in large populations have entailed extensive empirical analysis of naming conventions in different parts of the world without seeking any general or automated methods of population classification by ethno-cultural origin. Here we show how 'naming networks', constructed from forename-surname pairs of a large sample of the contemporary human population in 17 countries, provide a valuable representation of cultural, ethnic and linguistic population structure around the world. This innovative approach enriches and adds value to automated population classification through conventional national data sources such as telephone directories and electoral registers. The method identifies clear social and ethno-cultural clusters in such naming networks that extend far beyond the geographic areas in which particular names originated, and that are preserved even after international migration. Moreover, one of the most striking findings of this approach is that these clusters simply 'emerge' from the aggregation of millions of individual decisions on parental naming practices for their children, without any prior knowledge introduced by the researcher. Our probabilistic approach to community assignment, both at city level as well as at a global scale, helps to reveal the degree of isolation, integration or overlap between human populations in our rapidly globalising world. As such, this work has important implications for research in population genetics, public health, and social science adding new understandings of migration, identity, integration and social interaction across the world

Results of an Early Access Treatment Protocol of Daratumumab Monotherapy in Spanish Patients With Relapsed or Refractory Multiple Myeloma

Daratumumab is a human CD38-targeted monoclonal antibody approved as monotherapy for heavily pretreated relapsed and refractory multiple myeloma. We report findings for the Spanish cohort of an open-label treatment protocol that provided early access to daratumumab monotherapy and collected safety and patient-reported outcomes data for patients with relapsed or refractory multiple myeloma. At 15 centers across Spain, intravenous daratumumab (16 mg/kg) was administered to 73 patients who had >= 3 prior lines of therapy, including a proteasome inhibitor and an immunomodulatory drug, or who were double refractory to both. The median duration of daratumumab treatment was 3.3 (range: 0.03-13.17) months, with a median number of 12 (range: 1-25) infusions. Grade 3/4 treatment-emergent adverse events were reported in 74% of patients and included lymphopenia (28.8%), thrombocytopenia (27.4%), neutropenia (21.9%), leukopenia (19.2%), and anemia (15.1%). Common (>5%) serious treatmentemergent adverse events included respiratory tract infection (9.6%), general physical health deterioration (6.8%), and back pain (5.5%). Infusion-related reactions occurred in 45% of patients. The median change from baseline in all domains of the EQ-5D-5L and EORTC QLQ-C30 was mostly 0. A total of 18 (24.7%) patients achieved a partial response or better, with 10 (13.7%) patients achieving a very good partial response or better. Median progression-free survival was 3.98 months. The results of this early access treatment protocol are consistent with previously reported trials of daratumumab monotherapy and confirm its safety and antitumoral efficacy in Spanish patients with heavily treated relapsed or refractory multiple myeloma

Reaction rates and transport in neutron stars

Understanding signals from neutron stars requires knowledge about the transport inside the star. We review the transport properties and the underlying reaction rates of dense hadronic and quark matter in the crust and the core of neutron stars and point out open problems and future directions.Comment: 74 pages; commissioned for the book "Physics and Astrophysics of Neutron Stars", NewCompStar COST Action MP1304; version 3: minor changes, references updated, overview graphic added in the introduction, improvements in Sec IV.A.

Impact of prior therapy on the efficacy and safety of oral ixazomib-lenalidomide-dexamethasone vs placebo-lenalidomide-dexamethasone in patients with relapsed/refractory multiple myeloma in TOURMALINE-MM1

Prior treatment exposure in patients with relapsed/refractory multiple myeloma may affect outcomes with subsequent therapies. We analyzed efficacy and safety according to prior treatment in the phase 3 TOURMALINE-MM1 study of ixazomib-lenalidomide-dexamethasone (ixazomib-Rd) versus placebo-Rd. Patients with relapsed/refractory multiple myeloma received ixazomib-Rd or placebo-Rd. Efficacy and safety were evaluated in subgroups defined according to type (proteasome inhibitor [PI] and immunomodulatory drug) and number (1 vs 2 or 3) of prior therapies received. Of 722 patients, 503 (70%) had received a prior PI, and 397 (55%) prior lenalidomide/thalidomide; 425 patients had received 1 prior therapy and 297 received 2 or 3 prior therapies. At a median follow-up of ~15 months, PFS was prolonged with ixazomib-Rd vs placebo-Rd regardless of type of prior therapy received; HR 0.739 and 0.749 in PI-exposed and naive patients, HR 0.744 and 0.700 in immunomodulatory-drug-exposed and naive patients, respectively. PFS benefit with ixazomib-Rd vs placebo-Rd appeared greater in patients with 2 or 3 prior therapies (HR 0.58) and in those with 1 prior therapy without prior transplant (HR 0.60) versus those with 1 prior therapy and transplant (HR 1.23). Across all subgroups, toxicity was consistent with that seen in the intent-to-treat population. In patients with relapsed/refractory multiple myeloma, ixazomib-Rd was associated with a consistent clinical benefit vs placebo-Rd regardless of prior treatment with bortezomib or immunomodulatory drugs. Patients with 2 or 3 prior therapies, or 1 prior therapy without transplant seemed to have greater benefit than patients with 1 prior therapy and transplant. TOURMALINE-MM1 ClinicalTrials.gov: NCT01564537