Daratumumab-based regimens for patients with multiple myeloma plus extramedullary plasmacytomas or paraskeletal plasmacytomas: initial follow-up of an Italian multicenter observational clinical experience.

Myeloma with extramedullary plasmacytomas not adjacent to bone (EMP) is associated with an extremely poor outcome compared with paraosseous plasmacytomas (PP) as current therapeutic approaches are unsatisfactory. The role of new molecules and in particular of monoclonal antibodies is under investigation. To determine whether daratumumab-based regimens are effective for myeloma with EMP, we report herein an initial multicenter observational analysis of 102 myeloma patients with EMP (n = 10) and PP (n = 25) at diagnosis and EMP (n = 28) and PP (n = 39) at relapse, treated with daratumumab-based regimens at 11 Haematological Centers in Italy.EMP and PP at diagnosis were associated with higher biochemical (90% vs. 96%, respectively) and instrumental ORR (86% vs. 83.3%, respectively), while at relapse, biochemical (74% vs. 73%) and instrumental (53% vs. 59%) ORR were lower. Median OS was inferior in EMP patients compared with patients with PP both at diagnosis (21.0 months vs. NR) (p = 0.005) and at relapse (32.0 vs. 40.0 months) (p = 0.428), although, during relapse, there was no statistically significant difference between the two groups. Surprisingly, at diagnosis, median TTP and median TTNT were not reached either in EMP patients or PP patients and during relapse there were no statistically significant differences in terms of median TTP (20 months for two groups), and median TTNT (24 months for PP patients vs. 22 months for EMP patients) between the two groups. Median TTR was 1 month in all populations.These promising results were documented even in the absence of local radiotherapy and in transplant-ineligible patients.

Carfilzomib, lenalidomide, and dexamethasone in relapsed/refractory multiple myeloma patients: the real-life experience of Rete Ematologica Pugliese (REP).

Carfilzomib, lenalidomide, and dexamethasone (KRd) have been approved for the treatment of relapsed and refractory multiple myeloma (RRMM) based on ASPIRE clinical trial. However, its effectiveness and safety profile in real clinical practice should be further assessed. We retrospectively evaluated 130 consecutive RRMM patients treated with KRd between December 2015 and August 2018, in 9 Hematology Departments of Rete Ematologica Pugliese (REP). The overall response rate (ORR) was 79%, with 37% complete response (CR). Treatment with KRd led to an improvement in response regardless of age, refractory disease, and number and type of previous therapies. After a median follow-up of 18 months, median PFS was 24 months and 2y-PFS was 54%. PFS was longer in patients achieving a very good partial response (VGPR) with median PFS of 32.4 months. The relapses after prior autologous transplant (ASCT) positively impact median PFS. Several baseline disease characteristics, such as III ISS scoring or elevated LDH, and prior exposure to lenalidomide were found to negatively impact PFS. Primary refractory or relapsed myeloma patients have been treated with KRd as bridge to ASCT with a great benefit. Thirty-four (83%) reached at least a partial response after KRd and 21 (61%) performed ASCT. In transplanted patients, median PFS was not reached and 2y-PFS was 100%. The treatment discontinuation rate due to adverse events (AEs) was 18%, most commonly for lenalidomide (11%). Overall, in 10% of patients, a KRd dose reduction was necessary at least once (2.5% for carfilzomib and 8% for lenalidomide). The most frequent AE was neutropenia (44%) and anemia (41%). Infections occurred in 14% of patients. Cardiovascular events occurred in 11% of patients. Elderly patients have tolerated therapy very well, without additional side effects compared to younger patients, except for cardiac impairment. Our analysis confirmed that KRd is effective in RRMM patients. It is well tolerated and applicable to the majority of patients outside clinical trials. A longer PFS was shown in patients achieving VGPR, in those lenalidomide naïve and in patients relapsing after previous ASCT. Previous ASCT should not hamper the option for KRd therapy. Accordingly, KRd should be used as bridge regimen to ASCT with remarkable improvement in response and PFS rates. Further clinical studies are needed.

[The role of information and training for workers on the correct use of earplugs in assessing real noise attenuation with E-A-RfitTM system]. / Il peso di in\formazione e formazione dei lavoratori sul correctto utilizzo di inserti auricolari nella valutazione del reale abbattimento del rumore mediante il sistema E-A-Rfit ™.

BACKGROUND: Laboratory levels of perceived noise attenuation as heard using earplugs are always higher than the real levels that can be achieved at the workplace. The employer is bound by law to supply individual hearing protection devices (HPDs), to assess their efficiency and efficacy, and also to inform and train workers on the correct use of HPDs. OBJECTIVES: This study assessed the real "personal attenuation rating" (PAR) of HPDs  used by workers at the workplace, before (PAR A) and after (PAR B) specific and individual training. These values were also compared with the theoretical  "single number rating" (SNR) provided by the manufacturer. METHODS: The study covered all the 65 male employees of an awnings factory, using the E-A-RfitTM computerized method, which can measure PARs, based on the difference between sound pressures recorded by an "outside" microphone and an "inside" microphone placed in the auditory canal, with earplugs inserted, before (PAR A) and after (PAR B), i.e., the specific and individual training described above. RESULTS/CONCLUSIONS: PARs B were always definitely higher than PARs A, both for all tested frequencies and the corresponding average values, which were automatically detected by E-A-RfitTM. Furthermore the same PARs B were  decidedly lower than the respective SNRs supplied by the manufacturer on the basis of laboratory assessments. These data prove that specific and individual training for workers improves the performance of earplugs, contributing to a more appropriate secondary prevention of the effects of noise on hearing; they also prove that the real attenuation recorded in workers are always lower than those supplied by the manufacturer of the devices. It is recommended that the E-A-RfitTM system, which allowed these results to be achieved objectively, should be normally used to assess exposure to noise in workers, when HPDs are worn.