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We present a study of the metal-enriched halo gas, traced using MgII and [OII] emission lines, in two large, blind galaxy surveys - the MUSE (Multi Unit Spectroscopic Explorer) Analysis of Gas around Galaxies (MAGG) and the MUSE Ultra Deep Field (MUDF). By stacking a sample of ~600 galaxies (stellar masses M* ~10^{6-12} Msun), we characterize for the first time the average metal line emission from a general population of galaxy haloes at 0.7, 24 pages, 21 figures, 2 tables, accepted for publication in MNRAS

Bortezomib was the first proteasome inhibitor (PI) discovered and demonstrated great efficacy in myeloma, both in vitro and in patients. However, still many patients ultimately relapse and there is the need for novel therapies. A second generation of PI have been discovered, potentially more effective ands some also orally administered. Carfilzomib is an irreversible proteasome inhibitor that showed great efficacy in clinical studies. Ixazomib is an oral compound that has been introduced recently in the therapeutic spectrum. Novel agents such as Marizomib seem promising in the fact that can also pass through the blood brain barrier and maybe effective also in CNS muyeloma. This review focus on all proteasome inhibitors available in clinics and the new ones coming soon.

Abnormality of the B-cell receptor (BCR) signaling is correlated to origin of many B-cell malignancies.. Bruton’s tyrosine kinase (BTK), is described as a possible target in a many B-cell neoplasms. Ibrutinib is the most used inhibitor of BTK and has great tolerability and efficacy in chronic lymphocytic leukemia. This review summarizes results with ibrutinib in clinical trials and novel BTK inhibitors of interest.

Multiple myeloma survival has significantly improved in latest years, due to a broad spectrum of novel agents available for treatment. The introduction of thalidomide, bortezomib and lenalidomide together with autologous stem cell transplantation has dramatically prolonged complete remissions rate, progression free survivals resulting ultimately in prolonged survivals in myeloma patients. Moreover, novel strategies of treatment such as consolidation and maintenance are being used to implement responses. A number of new drugs such as carfilzomib and pomalidomide are already in clinical practice, and new kids on the block are entering, making the future of myeloma patients brighter.

The introduction of novel agents in multiple myeloma therapy has dramatically improved survival in latest years. Great progress has also been detected in particular poor clinical situation such as acute renal failure in which survival was dismal in the past. Treatment with bortezomib, thalidomide and dialysis associated with high cut-off (HCO) filters can recover more than two thirds of myeloma patients with an end stage renal failure. Novel proteasome inhibitors and immunomodulating agents (IMID's) are even more promising in this set of patients. Aim of this review is to provide an overview of treatments of multiple myeloma patients with acute renal failure coming from most recent clinical trials.

Median age at diagnosis for chronic lymphocytic leukaemia (CLL) patients is now 72 years, thus a consistent number of patients may not tolerate standard doses i.v. of fludarabine, cyclophosphamide and rituximab (FCR), the best available therapy, due to unacceptable myelotoxicity and risk of severe infections. We studied safety and efficacy of the addition of rituximab to the oral low-dose FC regimen (old-FCR) in a selected population of 30 elderly (median age 75, 15 untreated, 15 treated with 1 prior therapy) CLL patients. Complete remission (CR) rate was 80% in the untreated patients (overall response rate, ORR 93%), and 30% in pretreated patients (ORR 74%). Progression free survivals (PFS) were 45 months and 30 months in the untreated and treated patients, respectively. In patients achieving CR, old-FCR led to PFS of 67 months. Moreover, haematological toxicity was mild (grade 3-4: 15%) and patients were treated mostly in outpatient clinic. Old-FCR could be a good therapy option for elderly CLL patients outside clinical trials, larger studies are needed to confirm our findings.

A 71 year old female with multiple myeloma presented with back pain seven year after autologous stem cell transplant. Skeletal bone survey and magnetic resonance imaging did not show a relapse that was evidenced by CT/PET. Lenalidomide as single agent induced a complete disappearance of the lesions 6 months later and confirmed after one year at CT/PET.

6.02 (5.35-17.45); 3 IgG : 0.45 (0.15-1.07)) and 3 IgA (2.51 (1.994.94) which was not detected by IFE. In 9/9 patients the abnormal HLC ratio was seen in concordance with the clonality identified by FLC and in 7/9 patients the ratio was abnormal due to suppression rather than M protein production. Reductions in the dHLC or normalisation of the HLC ratio were concordant with both FLC assessment and clinical response in 4 patients (PR, VGPR and 2 CR). In the discordant patients, 4/5 achieved less than CR; in these patients the HLC ratio normalised but the uninvolved isotypematched immunoglobulin (uHLC) remained suppressed. For the remaining 1/5 discordant patient FLC levels normalised but the ratio stayed outside the normal range, consistent with CR; in this patient the HLC ratio was abnormal throughout due to stable but persistent suppression of the uninvolved HLC. Overall uHLC levels remained suppressed in all patients achieving less than CR, but only in 1/3 of those at CR. Conclusion: By using the HLC assay we were able to identify monoclonal immunoglobulin producing subclones in patients with light chain myeloma which were not detected by conventional techniques. In addition we found recovery of the uninvolved HLC correlated with depth of response in the majority of patients.

Abstract 1454 Deletion 13q14 (13q-) detected by fluorescence in situ hybridization (FISH) is the most frequent chromosomal abnormality in chronic lymphocytic leukemia (CLL). When 13q- is detected as sole abnormality has a good prognosis, while aggressive outcome is registered when 13q- is combined with other chromosomal abnormalities such as del 11q or del 17p. A recent study evidenced also that patients with higher percentage of 13q-deleted cells (>70%) are at higher risk for aggressive disease. Some studies evidenced that 13q- deletion size (involving D13S319 +/−Rb1) seems to matter in terms of time to treatment (TTT) and prognosis (OS). Few studies evaluated so far the incidence and prognosis of a biallelic 13q- deletion, i.e. the deletion of both alleles of the minimal deleted region (MDR) of chromosome 13q.In particular prognosis has been reported controversial. We analyzed at single institution 250 CLL patients by FISH in order to evaluate the incidence and prognosis of biallelic 13q- by using probes for D13S319 and RB1 that map to DLEU2/MIR15A/MIR16-1 and RB1 loci. Results were correlated in terms of TTT and OS with IGHV mutational status (mutated vs unmutated), RAI/BINET stage, CD38 positivity and/ or ZAP-70 positivity, beta-2M, LDH, other chromosomal abnormality (+12, del17p, del11q). Deletion 13q was considered present if >10% of nuclei were deleted out of 300 nuclei scored by two different and independent observers. All biallelic cases were confirmed by FISH using a probe for LSI-D13S319 and 13q34 to exclude false positive results. 135/250 (52%) patients presented a monoallelic del 13q. 45/135 (32%) presented a monoallelic del of RB1 while 20/135 (15%) cases presented a biallelic 13q-.12/20 (80%) presented a biallelic 13q- as sole abnormality, while 8/20 presented a 13q- associated with other cytogenetic abnormalities (one 17p-, five 11q-, two +12). The median percentage of 13q-deleted cells was 50% (range 14–86). Median age was 65 (range 50–85), M/F 12/8; 80% of the patients were RAI stage 0–1, while only 10% were RAI stage 4. No differences were seen in patients with biallelic deletion of 13q when LDH, b2M, ZAP-70,IGHV were considered. CD38 was negative in 16/20 patients. Regarding the MDR of chromosome 13q, 11/20 patients presented a biallelic del of D13S319, while 5/20 had a biallelic deletion of RB1; 5/20 patients presented a mono+biallelic del of D13S319 while 3/20 a mono+biallelic deletion of RB1. When we analyzed clinical and biological characteristics comparing patients with biallelic13q-,monoallelic 13q- and with no 13q-, we did not find differences in terms of: stage (RAI-Binet), P=0.2,P=0.9; B2 M, P=0.4; LDH,P=0.1; CD38 positivity, P=0.2; ZAP-70, P=0,1; IGHV M vs UM,P=0.65; P53 mutated vs wild type, P=0.1; del 11q was significantly associated more with biallelic 13q-, P=0.02. TTT and OS were not significantly different between biallelic 13q- patients and the other two groups (164 vs 212 vs 211, P=0.9). 8/20 patients with biallelic 13q- have been treated, all 5 patients carrying also a 11q- received treatment, the other 3 patients had: 1patient RB1 deletion in 92% of cells and 2 deletion 13q- in>75% of cells. In conclusion, biallelic 13q- are present in about 8% of all cases of CLL and in 15% of 13q- patients. A strong association with del 11q was found and this correlated with disease progression and treatment.CD38 was negative in the majority of patients with biallelic 13q-. RB1 was deleted in 32% of 13q- patients. No differences were found in terms of clinical characteristics, TTT and OS with monoallelic 13q-. Disclosures: No relevant conflicts of interest to declare.