Phase 1/2 study of weekly carfilzomib, cyclophosphamide, dexamethasone in newly diagnosed transplant-ineligible myeloma

This multicentre, open-label phase 1/2 trial determined safety and efficacy of weekly carfilzomib plus cyclophosphamide-dexamethasone (wKCyd) in newly diagnosed multiple myeloma (NDMM) patients aged ≥65 years or transplant ineligible. Patients received wKCyd for up to nine 28-day cycles, followed by maintenance with carfilzomib until progression/intolerance. The phase 1 portion used a 3+3 dose-escalation scheme to determine the maximum tolerated dose of weekly carfilzomib: 12 patients received wKCyd with carfilzomib doses of 45, 56 and 70 mg/m 2. The recommended phase 2 dose was established at 70 mg/m 2 and 54 patients (phase 1 and 2) received weekly carfilzomib 70 mg/m 2: 85% of them achieved ≥partial response (PR), 66% ≥very good PR, 30%≥near-complete response (CR) and 15% CR. Responses improved in 40 patients who started maintenance: 98% achieved ≥PR, including 29% CR and 10% stringent CR. After a median follow-up of 18 months, the 2-year progression-free survival and overall survival rates were 53.2% and 81%, respectively. The most frequent grade 3-5 toxicities were neutropenia (22%) and cardiopulmonary adverse events (9%). This is the first study of weekly carfilzomib plus an alkylating agent in elderly patients with NDMM. wKCyd was effective, with an acceptable risk/benefit ratio, and thus can be a valid option in this setting

Corrections to flat-space particle dynamics arising from space granularity

The construction of effective Hamiltonians describing corrections to flat space particle dynamics arising from the granularity of space at very short distances is discussed in the framework of an heuristic approach to the semiclassical limit of loop quantum gravity. After some general motivation of the subject, a brief non-specialist introduction to the basic tools employed in the loop approach is presented. The heuristical semiclassical limit is subsequently defined and the application to the case of photons and spin 1/2 fermions is described. The resulting modified Maxwell and Dirac Hamiltonians, leading in particular to Planck scale corrections in the energy-momentum relations, are presented. Alternative interpretations of the results and their limitations, together with other approaches are briefly discussed along the text. Three topics related to the above methods are reviewed: (1) The determination of bounds to the Lorentz violating parameters in the fermionic sector, obtained from clock comparison experiments.(2) The calculation of radiative corrections in preferred frames associated to space granularity in the framework of a Yukawa model for the interactions and (3) The calculation of synchrotron radiation in the framework of the Myers-Pospelov effective theories describing Lorentz invariance violations, as well as a generalized approach to radiation in Planck scale modified electrodynamics. The above exploratory results show that quantum gravity phenomenology provides observational guidance in the construction of quantum gravity theories and opens up the possibility of probing Planck scale physics.Comment: 49 pages, 6 figures and 4 tables. Extended version of the talk given at the 339-th WE-Heraeus-Seminar: Special Relativity, will it survive the next 100 years?, Potsdam, february 200

Lifetime measurements of N ≃ 20 phosphorus isotopes using the AGATA γ-ray tracking spectrometer

International audienceLifetimes of excited states of the phosphorus isotopes 1533,34,35,36P have been measured by using the differential recoil-distance method. The isotopes of phosphorus were populated in binary grazing reactions initiated by a beam of S36 ions of energy 225 MeV incident on a thin Pb208 target mounted in the Cologne plunger apparatus. The combination of the PRISMA magnetic spectrometer and an early implementation of the AGATA γ-ray tracking array was used to detect γ rays in coincidence with projectile-like nuclear species. Lifetime measurements of populated states were made within the range from about 1 to 100 ps. The number of states for which lifetime measurements were possible was limited by statistics. For P33, lifetime limits were determined for the first 3/2+ and 5/2+ states at 1431 and 1848 keV, respectively; the results are compared with previous published lifetime values. The lifetime of the first 2+ state of P34 at 429 keV was determined and compared with earlier measurements. For P35, the states for which lifetimes, or lifetime limits, were determined were those at 2386, 3860, 4101, and 4493 keV, with Jπ values of 3/2+, 5/2+, 7/21−, and 7/22−, respectively. There have been no previous published lifetimes for states in this nucleus. A lifetime was measured for the stretched π(1f7/2)⊗ν(1f7/2)Jπ=(7+) state of P36 at 5212 keV and a lifetime limit was established for the stretched π(1d3/2)⊗ν(1f7/2)Jπ=(5−) state at 2030 keV. There are no previously published lifetimes for states of P36. Measured lifetime values were compared with the results of state-of-the-art shell-model calculations based on the PSDPF effective interaction. In addition, measured branching ratios, published mixing ratios, and electromagnetic transition rates, where available, have been compared with shell-model values. In general, there is good agreement between experiment and the shell model; however there is evidence that the shell-model values of the M1 transition rates for the 3/21+→1/2+ (ground state) and 5/21+→3/21+ transitions in P33 underestimate the experimental values by a factor between 5 and 10. In P35 there are some disagreements between experimental and shell-model values of branching ratios for the first and second excited 7/2− states. In particular, there is a serious disagreement for the decay characteristics of the second 7/2− state at 4493 keV, for which the shell-model counterpart lies at 4754 keV. In this case, the shell-model competing electromagnetic decay branches are dominated by E1 and M1 transitions

Italian real life experience with brentuximab vedotin : results of a large observational study on 234 relapsed/refractory Hodgkin's lymphoma

A large Italian multicenter observational retrospective study was conducted on the use of brentuximab vedotin (BV) for patients with relapsed Hodgkin's lymphoma (HL) to check if clinical trial results are confirmed even in a real life context. 234 CD30+ HL patients were enrolled. Best response was observed after a median of 4 cycles in 140 patients (59.8%): 74 (31.6%) patients obtained a complete response (CR) and 66 (28.2%) achieved a partial response (PR); overall response rate at the end of the treatment was 48.3% (62 CR and 51 PR). The best response rate was higher in the elderly subset: 14 (50%) CR and 5 (17.8%) PR. Disease free survival was 26.3% at 3 years and progression free survival 31.9% at 4.5 years. Duration of response did not differ for who achieved at least PR and then either did or did not undergo consolidative transplant. Overall, the treatment was well tolerated and no death has been linked to BV-induced toxicity.Our report confirms activity in elderly patients, duration of response unrelated to the consolidation with transplant procedure, the relevance of the CR status at first restaging, and the role of BV as a bridge to transplant for chemorefractory patients

Quantum gravity phenomenology at the dawn of the multi-messenger era—A review

The exploration of the universe has recently entered a new era thanks to the multi-messenger paradigm, characterized by a continuous increase in the quantity and quality of experimental data that is obtained by the detection of the various cosmic messengers (photons, neutrinos, cosmic rays and gravitational waves) from numerous origins. They give us information about their sources in the universe and the properties of the intergalactic medium. Moreover, multi-messenger astronomy opens up the possibility to search for phenomenological signatures of quantum gravity. On the one hand, the most energetic events allow us to test our physical theories at energy regimes which are not directly accessible in accelerators; on the other hand, tiny effects in the propagation of very high energy particles could be amplified by cosmological distances. After decades of merely theoretical investigations, the possibility of obtaining phenomenological indications of Planck-scale effects is a revolutionary step in the quest for a quantum theory of gravity, but it requires cooperation between different communities of physicists (both theoretical and experimental). This review, prepared within the COST Action CA18108 “Quantum gravity phenomenology in the multi-messenger approach”, is aimed at promoting this cooperation by giving a state-of-the art account of the interdisciplinary expertise that is needed in the effective search of quantum gravity footprints in the production, propagation and detection of cosmic messengers.publishedVersio