Isatuximab plus pomalidomide and dexamethasone in patients with relapsed/refractory multiple myeloma according to prior lines of treatment and refractory status: ICARIA-MM subgroup analysis.

SB reports honoraria from Amgen, Bristol-Myers Squibb, Celgene, and Janssen; and reports a consultancy/advisory role for Celgene, Janssen, Karyopharm, and Takeda. VV reports a consultancy/advisory role for Astellas, Biocad, Bristol-Myers Squibb, Janssen, Roche, Sanofi, and Takeda. VM reports a consultancy/advisory role for Amgen, Bristol-Myers Squibb, Celgene, Janssen, and Takeda. LK reports honoraria from Amgen, Celgene, Janssen, and Takeda; a consultancy/advisory role for Amgen, Celgene, Janssen, and Takeda; and travel support from Amgen and Janssen. MP reports honoraria from Celgene, Pfizer, and Takeda; consultancy/advisory role for Amgen, Celgene, Janssen, Roche, and Takeda; and research funding from Amgen, Celgene, Janssen, Pfizer, Roche, and Takeda. PGR reports a consultancy/advisory role for Amgen, Janssen, Karyopharm, Oncopeptides, Sanofi, and Takeda; and research funding from Bristol-Myers Squibb, Celgene, Oncopeptides, and Takeda. LP, FV, KW, LB, and YK have no disclosures. FC, SLG, FM, and HvdV are employees of Sanofi

Moxetumomab pasudotox in heavily pre-treated patients with relapsed/refractory hairy cell leukemia (HCL): long-term follow-up from the pivotal trial

Background Moxetumomab pasudotox is a recombinant CD22-targeting immunotoxin. Here, we present the long-term follow-up analysis of the pivotal, multicenter, open-label trial (NCT01829711) of moxetumomab pasudotox in patients with relapsed/refractory (R/R) hairy cell leukemia (HCL). Methods Eligible patients had received ≥ 2 prior systemic therapies, including ≥ 2 purine nucleoside analogs (PNAs), or ≥ 1 PNA followed by rituximab or a BRAF inhibitor. Patients received 40 µg/kg moxetumomab pasudotox intravenously on Days 1, 3, and 5 of each 28-day cycle for up to six cycles. Disease response and minimal residual disease (MRD) status were determined by blinded independent central review. The primary endpoint was durable complete response (CR), defined as achieving CR with hematologic remission (HR, blood counts for CR) lasting > 180 days. Results Eighty adult patients were treated with moxetumomab pasudotox and 63% completed six cycles. Patients had received a median of three lines of prior systemic therapy; 49% were PNA-refractory, and 38% were unfit for PNA retreatment. At a median follow-up of 24.6 months, the durable CR rate (CR with HR > 180 days) was 36% (29 patients; 95% confidence interval: 26–48%); CR with HR ≥ 360 days was 33%, and overall CR was 41%. Twenty-seven complete responders (82%) were MRD-negative (34% of all patients). CR lasting ≥ 60 months was 61%, and the median progression-free survival without the loss of HR was 71.7 months. Hemolytic uremic and capillary leak syndromes were each reported in ≤ 10% of patients, and ≤ 5% had grade 3–4 events; these events were generally reversible. No treatment-related deaths were reported. Conclusions Moxetumomab pasudotox resulted in a high rate of durable responses and MRD negativity in heavily pre-treated patients with HCL, with a manageable safety profile. Thus, it represents a new and viable treatment option for patients with R/R HCL, who currently lack adequate therapy.publishedVersio

A comparison of random sequence reads versus 16S rDNA sequences for estimating the biodiversity of a metagenomic library

The construction of metagenomic libraries has permitted the study of microorganisms resistant to isolation and the analysis of 16S rDNA sequences has been used for over two decades to examine bacterial biodiversity. Here, we show that the analysis of random sequence reads (RSRs) instead of 16S is a suitable shortcut to estimate the biodiversity of a bacterial community from metagenomic libraries. We generated 10 010 RSRs from a metagenomic library of microorganisms found in human faecal samples. Then searched them using the program BLASTN against a prokaryotic sequence database to assign a taxon to each RSR. The results were compared with those obtained by screening and analysing the clones containing 16S rDNA sequences in the whole library. We found that the biodiversity observed by RSR analysis is consistent with that obtained by 16S rDNA. We also show that RSRs are suitable to compare the biodiversity between different metagenomic libraries. RSRs can thus provide a good estimate of the biodiversity of a metagenomic library and, as an alternative to 16S, this approach is both faster and cheaper

Genetically determined telomere length and multiple myeloma risk and outcome

This work was partially supported by intramural funds of Univerity of Pisa and DKFZ; by Fondo de Investigaciones Sanitarias (Madrid, Spain) [PI12/02688 to J. S., PI17/02276 to J.S.]; by Instituto de Salud Carlos III, co-funded by FEDER funds —a way to build Europe—[PI14-00613 to V.M.] and by Agency for Management of University and Research Grants (AGAUR) of the Catalan Government (Barcelona, Spain) [2017SGR723 to V.M.]. Open Access funding enabled and organized by Projekt DEAL.Telomeres are involved in processes like cellular growth, chromosomal stability, and proper segregation to daughter cells. Telomere length measured in leukocytes (LTL) has been investigated in different cancer types, including multiple myeloma (MM). However, LTL measurement is prone to heterogeneity due to sample handling and study design (retrospective vs. prospective). LTL is genetically determined; genome-wide association studies identified 11 SNPs that, combined in a score, can be used as a genetic instrument to measure LTL and evaluate its association with MM risk. This approach has been already successfully attempted in various cancer types but never in MM. We tested the "teloscore" in 2407 MM patients and 1741 controls from the International Multiple Myeloma rESEarch (IMMeNSE) consortium. We observed an increased risk for longer genetically determined telomere length (gdTL) (OR = 1.69; 95% CI 1.36-2.11; P = 2.97 x 10(-6) for highest vs. lowest quintile of the score). Furthermore, in a subset of 1376 MM patients we tested the relationship between the teloscore and MM patients survival, observing a better prognosis for longer gdTL compared with shorter gdTL (HR = 0.93; 95% CI 0.86-0.99; P = 0.049). In conclusion, we report convincing evidence that longer gdTL is a risk marker for MM risk, and that it is potentially involved in increasing MM survival.Univerity of PisaHelmholtz AssociationInstituto de Salud Carlos III PI12/02688 PI17/02276Instituto de Salud Carlos IIIEuropean CommissionFEDER funds-a way to build Europe PI14-00613Agency for Management of University and Research Grants (AGAUR) of the Catalan Government (Barcelona, Spain) 2017SGR723Projekt DEA

Détérioration respiratoire en sortie d'aplasie sous facteur de croissance hématopoïétique (G-CSF) (à propos de 20 cas)

Des cas d aggravation respiratoire en sortie d aplasie ont été décrits chez les patients d onco-hématologie. Le G-CSF aggrave la toxicité pulmonaire de la chimiothérapie et le SDRA en sortie d aplasie (SDRA-SA) chez le rat. Peu de données cliniques sont disponibles. Nous rapportons 20 patients admis en réanimation pour détérioration respiratoire en SA post-chimiothérapie sous G-CSF (12 lymphomes, 5 leucémies, 2 cancers et un myélome ; 8 autogreffes de CSP et 2 allogreffes de moelle). Une pneumopathie avait compliqué la neutropénie chez tous les patients. Malgré un recours à la VNI chez 5 patients et invasive chez 13, seuls 5 patients sont décédés ; les autres ont guéri après arrêt du G-CSF, traitement anti-infectieux et symptomatique. Nous souhaitons alerter les cliniciens ayant en charge des patients sous G-CSF. Devant une suspicion de SDRA-SA, nous recommandons l arrêt du G-CSF, l élimination de toute autre cause de pneumopathie et l utilisation précoce de la VNI en réanimation.Some reports suggest the possibility of respiratory deterioration during neutropenia recovery (NR) in cancer patients. G-CSF aggravates chemotherapy-related pulmonary toxicity, and ARDS during NR in rats. Few clinical data are available. We report 20 cases of critically ill cancer patients admitted for acute respiratory deterioration during G-CSF induced NR: 12 lymphomas, 5 leukemias, 2 solid cancers and 1 myeloma. Eight patients underwent autologous transplantation, 2 allogeneic transplantation. All presented pneumonia increasing during NR. Despite the need of mechanical ventilation (MV) in 16 patients, only 5 died; others were cured after G-CSF interruption, antimicrobiol therapy and supportive care. Clinicians must be aware that during G-CSF induced NR, patients are at high risk of respiratory deterioration, above all if they present with prior lung involvement. In such cases, we recommend interruption of G-CSF, exclusion of other cause of respiratory failure and early NIMV in ICU.PARIS12-CRETEIL BU Médecine (940282101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Real life management of patients hospitalized with multiple myeloma in France.

Patients with multiple myeloma included in prospective clinical trials are highly selected and therefore are expected not to be representative of the entire patient population. Additionally recommendations based on literature data and randomized trials are not systematically implemented in all patients. We sought to determine how patients hospitalized with a diagnosis of multiple myeloma are currently treated in France.We performed a nation-wide search using the Programme de Médicalisation des Systèmes d'Information (PMSI) database which includes anonymous data for all patients hospitalized in France. We identified newly diagnosed cases in 2012 and analyzed the number and duration of hospital stays, coexisting conditions and treatment modalities with data available until the end of 2015. A diagnosis of multiple myeloma was determined for the first time during a hospitalization in France in 2012 in 6,282 patients (3,234 males and 3,048 females). The median age at diagnosis was 74 years (72 in males and 76 in females). A majority (55.3%) of patients were diagnosed and treated in a single heath center, including 37% in a university hospital and 52% in a non-university public hospital. Comorbidities potentially impacting on myeloma treatment were present in 57.5% of patients at diagnosis, and 15% had an associated diagnosis of another neoplasia. Intensive therapies with stem cell transplants were performed in 1033 patients (16% of total), the majority of which were aged less than 65 (881 patients, 85.3%). Stem cell transplants were performed more frequently in males while the distance between the site of residence and the transplant center had no impact on likelihood of receiving a transplant. Only 60% of patients less than 65 years old who were treated for their disease underwent intensification with stem cell transplant within the 4-year follow-up period.A large majority of patients hospitalized with a diagnosis of multiple myeloma are elderly, in particular females, and not eligible for transplants. Among the patients aged less than 65 and receiving therapy for their disease, 40% do not undergo transplants. These data emphasize the need for alternative therapies

Continued survival gains in recent years among critically ill myeloma patients.

International audienceOBJECTIVE: Therapeutic advances have improved survival in patients with myeloma (MM) over the past decade. We investigated whether survival has also improved in critically ill myeloma patients. DESIGN: Retrospective study. SETTING: Intensive care unit. PATIENT: Consecutive myeloma patients admitted to a teaching hospital ICU between 1990 and 2006. We compared three year-of-admission groups (1990-1995, 1996-2001, and 2002-2006) that matched changes in myeloma treatment (chemotherapy only, stem cell transplantation, and new molecules, respectively). INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: We included 196 patients. Reasons for ICU admission and patient characteristics were similar across groups; however, less use of conventional chemotherapy and radiotherapy and greater use of steroids were noted in the more recent periods. Over time, vasopressors and invasive mechanical ventilation were used decreasingly, and noninvasive ventilation increasingly, to treat acute respiratory failure. Hospital mortality decreased from 75% in 1990-1995 to 49% in 1996-2001 and 40% in 2002-2006 (P = 0.0007). Mortality was associated with poor performance status [OR 2.27, 95% CI (1.04-4.99)], need for mechanical ventilation [OR 4.33, 95% CI (1.86-10.10)], need for vasopressors [OR 2.57, 95% CI (1.12-5.86)], and admission for an event related to myeloma progression [OR 2.77, 95% CI (1.13-6.79)]. ICU admission within 48 h after hospital admission was associated with lower mortality [OR 0.28, 95% CI (0.19-0.89)]. CONCLUSION: Hospital mortality decreased significantly over the last 15 years in myeloma patients admitted to the ICU. Risk factors for death were organ failure and poor chronic health status. Early ICU admission was associated with lower mortality, suggesting opportunities for further improving survival

Monitoring NK cell activity in patients with hematological malignancies

International audienceNatural killer (NK) cells are lymphocytes of the innate immune system that can recognize and kill various types of malignant cells. Monitoring the activity of peripheral NK cells in patients affected by hematological malignancies may provide prognostic information or unveil ongoing tumor-specific immune responses. Moreover, further insights into the biology of NK cells might also promote the development of novel strategies for stimulating their anticancer activity. Here, we review the main methods to monitor phenotypic and functional NK cell properties in cancer patients, focusing on individuals affected by multiple myeloma, a hematological malignancy currently treated with immunomodulatory drugs

Netrin-1 expression and targeting in multiple myeloma

International audienc