Abstract: Pulsed dye laser (PDL) treatment of port‐wine stains (PWSs) in children is a common procedure performed in most laser units. Pain assessment in our younger patients is a major concern, especially in those with extensive PWSs. The use of general anesthesia (GA) results in pain‐free treatment, but its effects on the developing brain are far from totally understood. Thus we propose some tips that avoid the use of GA in most of our young patients, including the use of topical anesthetics and cooling systems, large laser spot size and high frequencies, early and frequent treatment with parents present, and the “introduction” and “pressure” techniques, among others.

Abstract: A promising cancer target in multiple myeloma is overexpressed heat shock protein 90, which is crucial in buffering the high levels of proteotoxic stress characteristic of this disease. This phase 1/1B trial shows disease stabilization with the small molecule heat shock protein 90 inhibitor NVP‐AUY922 with or without bortezomib in patients with relapsed or refractory multiple myeloma. Increased therapeutic success should be reachable by mutual inhibition of survival feedback loops (eg, additional heat shock protein 70 inhibition).

Abstract: Continuous treatment with lenalidomide (R) and dexamethasone (d) is a standard of care for multiple myeloma (MM) patients (pts) not candidates for autologous stem cell transplantation (ASCT). As previously reported, the addition of Clarithromycin (C) to Rd has proven to be safe and effective, and case-control analyses suggested a significant additive value with the combination. C optimizes the therapeutic effect of glucocorticoids by increasing the area under the curve, has immunomodulatory effects and may have direct antineoplastic properties. However, there are not randomized phase III trials confirming these results. GEM-Claridex in an open, randomized, phase III trial for untreated newly diagnosed MM pts ineligible for ASCT. Enrolled pts were randomly assigned 1:1 to receive 28-day cycles of R (25mg po qd days 1-21), d (40mg po [20mg in pts & gt;75 years], days 1, 8, 15 and 22) plus or minus C (500mg po bid) until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall response rate (ORR), overall survival (OS) and minimal residual disease (MRD) negativity rate and safety. MRD was evaluated in 99 pts using Euroflow NGF (limit of detection, 2x10-6). As expected, most pts in CR were tested for MRD whereas the majority of pts with missing MRD data achieved VGPR or less and were thus considered as MRD-positive for intent to treat analyses. Two hundred and eighty-eight pts were included (144 to C-Rd and 144 to Rd). Median age was 76 (range: 65-93), 36.8% of pts had ISS 3 and 15.6% presented with high-risk cytogenetic abnormalities. Key baseline characteristics were well balanced between the two arms. The addition of C to Rd resulted in deeper responses with a ≥ complete response (CR) rate of 20.1% in the C-Rd arm compared to 11.2% in the Rd arm (p = 0.037). Also, the ≥ very good partial response (VGPR) rate was 52.8% in the C-Rd arm as compared to the 37.1% in the Rd arm (p = 0.007). MRD analysis was performed at suspected CR and yearly afterwards. On intent-to-treat, 5/144 (3,5%) and 9/143 (6,2%) of pts achieved undetectable MRD with C-Rd and Rd, respectively (p = 0,7). With a median follow-up of 16 months (range, 1-47), no significant differences were observed in PFS: in the C-Rd arm the median was 23 months and has not been reached in the Rd arm (p = 0.09); furthermore, although disease progression and/or death rate was comparable in both arms (C-Rd: 57/144 [39.6%] vs Rd: 45/144 [31.2%] ), a trend towards shorter PFS was observed in the C-Rd group (Figure 1). This effect was less evident in younger ( & lt;75) pts (median PFS, C-Rd: 24 months vs Rd NR, p = 0,588) but, in older pts (≥ 75), the addition of C to Rd resulted into a significant deleterious effect on PFS (median PFS, C-Rd: 19 vs Rd 28 months, p = 0.03) (Figure 2a and 2b). Irrespectively of treatment arm, pts with MRD negative had significantly longer PFS (NR vs 26 months, p = 0,03). Concerning OS, no differences have been identified (p = 0.41), although median has not been reached yet in any arm. Out of the 33 and 28 deaths documented in the C-Rd and Rd arms respectively, the percentage of pts dying w/o documented PD was significantly higher in the C-Rd group (27/33 [82%] vs 13/27 [48%] , p = 0.004). Furthermore, in the C-Rd arm, the most frequent causes of death were severe infections (14/27 [52%] and cardiovascular events 6/27 [22%] ) the majority of them occurring in older (≥75) pts (20/27, 74%). The most common G3-4 adverse events (AE) in the C-Rd and Rd arms were hematologic (neutropenia: 10,4% vs 16,7% [p = ns] and anemia: 2,1% vs 6,9% [p = 0,04] , respectively). G3-4 infections occurred in 16% of cases in both arms and were the most frequent non-hematological AE. 7% of pts in both arms developed G3-4 GI toxicity and there were no differences between the two arms in G3-4 skin-related AEs (2,8% vs 3,5%). Only one case of invasive SPM (colon cancer) in the C-Rd arm was reported. In conclusion, the addition of C to Rd in transplant ineligible newly diagnosed MM pts significantly increases the rate and depth of responses but it is not associated with an improved PFS and OS due to a higher proportion of deaths in the C-Rd arm, mostly infectious, in pts & gt; 75 years and being early deaths. Overexposure to steroids due to the delayed clearance induced by C in this elderly population could explain our results. Figure Disclosures Puig: The Binding Site: Honoraria; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Takeda: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Research Funding. Rosinol Dachs:Janssen, Celgene, Amgen and Takeda: Honoraria. De Arriba:Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Takeda: Honoraria. Oriol:Celgene Corporation: Consultancy, Speakers Bureau; Takeda: Consultancy, Speakers Bureau; Janssen: Consultancy; Amgen: Consultancy, Speakers Bureau. De La Rubia:AbbVie: Consultancy; AMGEN: Consultancy; Celgene Corporation: Consultancy; Takeda: Consultancy; Janssen: Consultancy. Amor:Celgene: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees. Martín Sánchez:GILEAD SCIENCES: Research Funding. Rossi:BMS: Research Funding; Janssen, Celgene, Amgen: Consultancy. Coleman:Merck: Research Funding; Pharmacyclics: Speakers Bureau; Kite Pharmaceuticals: Equity Ownership; Gilead, Bayer, Celgene: Consultancy, Research Funding, Speakers Bureau. Paiva:Amgen, Bristol-Myers Squibb, Celgene, Janssen, Merck, Novartis, Roche, and Sanofi; unrestricted grants from Celgene, EngMab, Sanofi, and Takeda; and consultancy for Celgene, Janssen, and Sanofi: Consultancy, Honoraria, Research Funding, Speakers Bureau. San-Miguel:Amgen, Bristol-Myers Squibb, Celgene, Janssen, MSD, Novartis, Roche, Sanofi, and Takeda: Consultancy, Honoraria. Bladé:Jansen, Celgene, Takeda, Amgen and Oncopeptides: Honoraria. Niesvizky:Takeda, Amgen, BMS, Janssen, Celgene: Consultancy, Research Funding. Mateos:EDO: Membership on an entity's Board of Directors or advisory committees; Pharmamar: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; GSK: Membership on an entity's Board of Directors or advisory committees; Adaptive: Honoraria.

Abstract: INTRODUCTION: Multiple myeloma (MM) is most frequently diagnosed among people aged 65-74, and approximately one-third of patients (pts) are aged ≥75 years. Advanced age has a negative effect on the prognosis of pts with MM. The randomized, open-label, active-controlled, multicenter phase 3 ICARIA-MM study (NCT02990338) compared treatment with the anti-CD38 monoclonal antibody isatuximab (Isa) in combination with pomalidomide and dexamethasone (Pd) with Pd. Pts had relapsed/refractory MM (RRMM) after ≥2 prior lines of therapy, including lenalidomide and a proteasome inhibitor. This subgroup analysis of ICARIA-MM examined efficacy and safety in elderly pts (≥75 years) compared with younger pts. METHODS: Pts were randomized (1:1) to receive Isa-Pd or Pd. Isa (10 mg/kg IV) was given on days 1, 8, 15, and 22 (cycle 1), and days 1 and 15 in subsequent 28-day cycles. All pts received pomalidomide 4 mg on days 1-21 of each cycle and dexamethasone 40 mg (20 mg for pts ≥75 years old) on days 1, 8, 15, and 22 of each cycle. The primary endpoint was progression-free survival (PFS), assessed by an independent response committee. Subgroup analyses were conducted for pts aged 〈 65, 65-74, and ≥75 years of age. RESULTS: Overall, 307 pts were randomized to Isa-Pd (n=154) or Pd (n=153) and included in the intent-to-treat population. The median age of pts was 68.0 years in the Isa-Pd arm and 66.0 years in the Pd arm. In the Isa-Pd and Pd arms, there were 54 (35%) and 70 (46%) pts 〈 65 years of age, 68 (44%) and 54 (35%) pts 65-74 years of age, and 32 (21%) and 29 (19%) pts ≥75 years of age, respectively. In the overall population, PFS was significantly improved with Isa-Pd versus Pd (median 11.53 vs 6.47 months; hazard ratio [HR] 0.596; 95% confidence interval [CI] 0.436-0.814; p=0.001). Consistent with this, pts ≥75 years of age had a median PFS of 11.40 with Isa-Pd vs 4.47 months with Pd (HR 0.479; 95% CI 0.242-0.946). Similarly, in the Isa-Pd and Pd groups, pts 65-74 years of age had a PFS of 11.57 and 8.58 months (HR 0.638; 95% CI 0.385-1.059); in pts 〈 65 years of age, PFS was 11.53 vs 5.03 months, respectively (HR 0.656; 95% CI 0.401-1.074). Overall response rate (ORR) for all pts was 60.4% with Isa-Pd and 35.3% with Pd with an odds ratio (OR) of 2.80 (95% CI 1.72-4.56). ORR by age group in pts receiving Isa-Pd vs Pd was: 53.1% and 31.0% in the ≥75 years group (OR 2.52; 95% CI 0.79-8.26); 64.7% and 38.9% in the 65-74 years group (OR 2.88; 95% CI 1.29-6.46); and 59.3% and 34.3% in the 〈 65 years group (OR 2.79; 95% CI 1.26-6.20). At least a very good partial response (≥VGPR) was achieved by 31.8% of pts with Isa-Pd and 8.5% with Pd, with an OR of 5.03 (95% CI 2.51-10.59). Rates of ≥VGPR by age in pts receiving Isa-Pd vs Pd was: 31.3% and 0% in the ≥75 years group (OR not calculated); 32.4% vs 13.0% in the 65-74 group (OR 3.21; 95% CI 1.17-9.70); and 31.5% and 8.6% in the 〈 65 years group (OR 4.90; 95% CI 1.64-16.35). Of 8 pts with negative minimal residual disease at 10−5, 2 were ≥75 years old. At the time of analysis, overall survival (OS) data are not yet mature. However, in the elderly population, 8/32 (25%) pts in the Isa-Pd arm had died with median OS not reached, and in the Pd arm, 15/29 (51.7%) had died with a median OS of 10.25 months (HR 0.404; 95% CI 0.171- 0.956). In the Isa-Pd arm, the incidence of all-grade treatment-emergent adverse events (TEAEs) across age groups was: 〈 65 years, 98.1%; 65-74 years, 100%; and ≥75 years, 100%. There were more Grade ≥3 TEAEs with Isa-Pd in pts aged ≥75 years (93.8%) compared with pts 〈 65 years of age (85.2%), with a similar trend observed in the Pd arm (75.0% and 64.7%, respectively). There were also more treatment discontinuations because of TEAEs in pts ≥75 vs 〈 65 years of age in the Isa-Pd arm (15.6% and 7.4%, respectively) and in the Pd arm (14.3% and 10.3%). There was a higher incidence of serious TEAEs (SAEs) in pts ≥75 vs 〈 65 years of age in both arms (Isa-Pd, 68.8% and 57.4%; Pd, 57.1% and 47.1%, respectively). The incidence of TEAEs with fatal outcome was lower in pts aged ≥75 years in the Isa-Pd arm (6.3%) than in pts 〈 65 years (11.1%), while the opposite trend was observed with Pd (14.3% vs 5.9%). CONCLUSION: The addition of Isa to Pd improved PFS, ORR, ≥VGPR, and OS in elderly pts, consistent with the benefit observed in the overall study population. There was a consistent trend toward higher rates of SAE and discontinuation due to TEAEs in elderly pts in both the Isa-Pd and Pd arms, but with no increase in fatal AEs in the Isa-Pd arm. Disclosures Schjesvold: Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria; SkyliteDX: Honoraria; Oncopeptides: Membership on an entity's Board of Directors or advisory committees; MSD: Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees. Richardson:Sanofi: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb: Research Funding; Oncopeptides: Membership on an entity's Board of Directors or advisory committees, Research Funding; Karyopharm: Membership on an entity's Board of Directors or advisory committees. Facon:Sanofi: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Alegre:Celgene, Amgen, Janssen, Takeda: Membership on an entity's Board of Directors or advisory committees. Spencer:Janssen Oncology: Other: Consulting/advisory role, Research Funding, Speakers Bureau; Amgen: Other: Consulting/advisory role, Research Funding; AbbVie: Other: Consulting/advisory role, Research Funding; Servier: Other: Consulting/advisory role; Takeda: Other: Consulting/advisory role, Research Funding; Secura Bio: Other: Consulting/advisory role; Haemalogix: Other: Consulting/advisory role; Celgene: Other: Consulting/advisory role, Research Funding, Speakers Bureau; Sanofi: Other: Consulting/advisory role; Specialised Therapeutics Australia: Consultancy, Honoraria. Sunami:Ono: Honoraria, Research Funding; Takeda: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Bristol-Myers Squibb: Honoraria, Research Funding; Alexion-pharma: Research Funding; GSK: Research Funding; Janssen: Research Funding; Daiichi Sankyo: Research Funding; Sanofi: Research Funding; MSD: Research Funding; Novartis: Research Funding; Abbvie: Research Funding. Le-Guennec:Sanofi: Employment. Campana:Sanofi: Employment. van de Velde:Sanofi: Employment. Bensfia:Sanofi: Employment. Bringhen:Bristol-Myers Squibb: Honoraria; Celgene Corporation: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy.

Abstract: Introduction: In recent years, the multiple myeloma (MM) treatment (Tx) landscape has evolved considerably, with the approval of effective novel agents, such as immunomodulatory drugs (thalidomide, lenalidomide, and most recently, pomalidomide) and proteasome inhibitors (bortezomib and carfilzomib; Chng et al, Leukemia, 2014). However, most patients relapse and patterns of relapse in MM can be heterogeneous (Alegre et al, Haematologica, 2002). Tx rescue for MM relapse should begin at symptomatic clinical relapse (clinR) and probably earlier at asymptomatic biological relapse (BR; specifically when significant paraprotein relapse), according to the International Myeloma Workshop Consensus Panel (Rajkumar et al, Blood, 2011). In the case of asymptomatic BR/progression, rescue Tx could be delayed in a subset of pts (Fernández de Larrea et al, Bone Marrow Transplant, 2014), particularly when M-component and hemoglobin levels are stable. Progressive increases of M-spike blood and/or urine could lead to rescue Tx, even in the absence of clinical symptoms, to avoid complications (ie, renal failure, plasmacytomas, bone lesions; Castelli et al, Clin Med Insights Oncol, 2013). This Spanish registry (EPA-MMBR) is an observational prospective study to describe MM relapse patterns, comparing the impact of Tx decisions (starting Tx at BR vs delaying Tx until clinR). We present the updated preliminary results of this study. Methods: MM pts in (or prior to) first or second BR who had achieved ≥ PR since their last Tx were included. Bi-monthly evaluations were performed. Forty-one Spanish sites are participating after approval from their independent ethics committees, with 410 pts expected to be included. The main objective was to assess time to progression (TTP) from BR in both groups (pts who started Tx at the onset of asymptomatic BR vs pts who started Tx at clinR). Secondary objectives included demographic, clinical, and Tx characteristics; median time from BR to clinR; and response rates. Here we present the results of 138 pts with baseline data (48.4%) of a total of 285 registered. Results: In the cohort evaluated (n = 138), mean age was 67.9 years, and 50.7% were male. MM types were IgG Κ (43.5%), IgG λ (22.1%), IgA Κ (16%), and IgA λ (7.6%). Prognostic stage at diagnosis according to the International Staging System (ISS) was II (32.6%) followed by I and III (22.7% each) and data not available (22%). Pts' cytogenetic risk included standard risk (20.8%), high risk (8.5%), and no cytogenetic alterations (32.3%). More than half of pts (51.5%) had received autologous stem cell transplant, 13.2% consolidation and 21.1% maintenance. After first-line Tx, pts had achieved sCR (16.0%), CR (33.6%), VGPR (28.8%), or PR (21.6%). Pts with BR had a median time from diagnosis to BR of 2.66 years. Tx was delayed until clinR in 51.2% of pts, and 48.8% had started Tx at BR (73.3% of whom had significant paraprotein relapse; Figure); there were no relevant differences in demographic and clinical characteristics between the 2 groups. Median time to BR was 31.97 months. Median time from BR to clinR was 105.0 days. Among pts who started Tx at BR, most pts received lenalidomide-based Tx (75% at first relapse and 70.6% at second relapse). At the time of the analysis, only 3 pts had disease progression (1 in each group). In pts who started Tx at BR, first-line Tx after diagnosis was mainly bortezomib-based (73.3%). sCR was achieved in 20.0% of pts, CR in 33.3%, PR in 26.7%, and VGPR in 20.0%. Since the beginning of the study, Tx was prescribed in 54 pts (39.1%). Since only 3 pts had progressed, further follow-up data, particularly in terms of TTP and survival, are needed to identify differences between these 2 strategies. Conclusions: To our knowledge, this is the first prospective study in MM that evaluates the effects of starting Tx at BR vs starting Tx at clinR. In this updated cohort, we find that almost half of pts started Tx at BR (48.8%). We also found that a higher percentage of pts started Tx at BR with significant paraprotein relapse (73.3%), which seems to be a clear factor guiding Tx decision for the physician. Further follow-up and a complete study are needed to identify the differences between these 2 strategies and to define patients who could benefit from early Tx. Figure 1. Percentage of pts who started Tx at clinR, BR, or significant paraprotein relapse (n = 138). Figure 1. Percentage of pts who started Tx at clinR, BR, or significant paraprotein relapse (n = 138). Disclosures Gironella: Celgene Corporation: Consultancy, Honoraria. Fernández de Larrea:Celgene Corporation: Consultancy, Honoraria; Janssen: Consultancy, Honoraria. Lahuerta:Celgene Corporation: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen Cilag: Honoraria, Membership on an entity's Board of Directors or advisory committees. Cabañas:Amgen: Membership on an entity's Board of Directors or advisory committees. Lostaunau:Celgene SLU: Employment. Vilanova:Celgene SLU: Employment. Alegre:Celgene Corporation: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees.

Abstract: Introduction: The GEM-CESAR trial is a potentially curative strategy for high-risk smoldering multiple myeloma (HRsMM) patients in which the primary endpoint is the assessment of bone marrow minimal residual disease negativity by next generation flow (NGF). However, alternative methods of tumor burden evaluation in serum, like Quantitative Immunoprecipitation Mass Spectrometry (QIP-MS), a polyclonal antibody-based technology to identify intact immunoglobulins, have been also evaluated. Patients and Methods: Ninety HRsMM patients included in the GEM-CESAR trial received six 4-weeks cycles of carfilzomib, lenalidomide and dexamethasone followed by high dose melphalan and ASCT and 2 further cycles of consolidation with the same regimen. All patients received maintenance with lenalidomide up to 2 years. SPEP and IFE were performed using standard procedures and MRD was analyzed by flow cytometry following EuroFlow recommendations. QIP-MS assessment has been previously described (1) and allowed us the characterization of the isotype of each Ig trough immunoprecipitation with paramagnetic beads as well as the measurement of the molecular mass of each Ig for each specific patient, with enough precision and accuracy to establish clonality. Standard response assignment was carried out as per the IMWG guidelines. Results: First, we confirmed the higher sensitivity of QIP-MS to identify the presence of a serum M-spike as compared to conventional protein immunofixation electrophoresis methods. Amongst patients in CR, QIP-MS identified the M-spike in 18/30 (60%) post-induction, 18/47(38%) post-ASCT and 25/58(43%) post-consolidation. Interestingly, similar results were obtained with MRD-NGF post-induction [17/30(57%)] and post-ASCT [15/47(32%)] although the positive rate post-consolidation [15/58(26%)] was higher with QIP-MS. Then, we analyzed the overall concordance between the results obtained with QIP-MS and MRD-NGF at the three timepoints of disease evaluation, finding an overall concordance of 81% post-induction (n=76), 70% post-transplant (n=76) and 68% post-consolidation (n=77). Thus, when compared to the results of MRD-NGF, QIP-MS demonstrated sensitivities of 100%, 79% and 77% post-induction, post-ASCT and post-consolidation, and negative predictive values (NPV) of 100%, 79% and 82% at each respective time-point. (P & lt; 0,0001; P = 0,0004; P = =,0012) Evaluation of discrepant cases showed 14 out of 22 MRD-NGF-negative patients post-induction for whom QIP-MS identified a M-spike; in some cases (i.e. IgG MM isotype) this may be related to a longer immunoglobulin half-life. There were no cases with detectable disease by NGF but QIP-MS negative. By contrast, post-ASCT, QIP-MS was negative in seven MRD-positive patients, two of whom became MRD-NGF-negative after consolidation; at last follow-up, none of them have progressed. On the other hand, sixteen patients with negative MRD-NGF after ASCT had a detectable M-spike by mass spectrometry. Of note, the M-spike became undetectable after consolidation in six out of these 16 patients. Post-consolidation, there were 7 patients in which MRD-NGF was positive but QIP-MS negative: MRD evaluation during maintenance is pending but none of them have so far progressed. By contrast, there were 18 patients with the M-spike detectable by QIP-MS but MRD-NGF negative: follow-up of these patients will address their outcome but, the only patient that has progressed so far had MRD-NGF negative post-induction, becoming positive post-transplant and consolidation, but the M-spike was detectable by QIP-MS throughout. Conclusions: M-spike monitoring by QIP-MS shows a moderate concordance with the MRD assessment by NGF in this group of HRsMM homogeneously treated. Longer follow-up will allow us to unravel the outcome of discordant cases and to define the specificity of QIP-MS and its complementary value to NGF. North S, Barnidge D, Brusseau S, Patel R, Haselton M, Du Chateau B, et al. QIP-MS: A specific, sensitive, accurate, and quantitative alternative to electrophoresis that can identify endogenous m-proteins and distinguish them from therapeutic monoclonal antibodies in patients being treated for multiple myeloma. Clinica Chimica Acta 2019;493:S433. Disclosures Puig: Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Research Funding; The Binding Site: Honoraria; Takeda, Amgen: Consultancy, Honoraria. Mateos:Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Adaptive: Honoraria; GSK: Membership on an entity's Board of Directors or advisory committees; Pharmamar: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; EDO: Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees. Paiva:Amgen, Bristol-Myers Squibb, Celgene, Janssen, Merck, Novartis, Roche, and Sanofi; unrestricted grants from Celgene, EngMab, Sanofi, and Takeda; and consultancy for Celgene, Janssen, and Sanofi: Consultancy, Honoraria, Research Funding, Speakers Bureau. Rodriguez Otero:Takeda: Consultancy; Kite Pharma: Consultancy; BMS: Honoraria; Celgene Corporation: Consultancy, Honoraria, Speakers Bureau; Janssen: Consultancy, Honoraria. Oriol:Celgene, Amgen, Takeda, Jansse: Consultancy, Speakers Bureau. Rios:Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees. Alegre:Celgene, Amgen, Janssen, Takeda: Membership on an entity's Board of Directors or advisory committees. de la Rubia:AbbVie: Consultancy; Janssen: Consultancy; Amgen: Consultancy; Celgene: Consultancy; Takeda: Consultancy. De Arriba:Amgen: Consultancy, Honoraria; Takeda: Honoraria; Janssen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria. Ocio:Mundipharma: Research Funding; Pharmamar: Consultancy; Amgen: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria; AbbVie: Consultancy; Takeda: Consultancy, Honoraria; Array Pharmaceuticals: Research Funding; Sanofi: Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Seattle Genetics: Consultancy; Novartis: Consultancy, Honoraria; BMS: Honoraria. Bladé:Janssen, Celgene, Amgen, Takeda: Membership on an entity's Board of Directors or advisory committees; Irctures: Honoraria. Lahuerta:Takeda, Amgen, Celgene and Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees.

Abstract: INTRODUCTION: Ibrutinib is a first-in-class Bruton kinase inhibitor (BTK) registered for the treatment of Chronic Lymphocytic Leukemia (CLL), mantle cell linphoma (MCL) and Waldenström Macroglobulinemia (WM). Increased risk of bleeding events is asociated with ibrutinib, mostly grade ≤2. Alleged mechanism for this risk could be the role of BTK in platelet activation via GPIb, GPVI and FVW. We here present our experience regarding hemorragic events and hemostasis tests alterations in CLL patients (pts) treated with ibrutinib. PATIENTS AND METHODS: 15 pts with relapsed CLL were started on ibrutinib between december/2012 and july/2016. Median age was 69 years (range: 42-83 years). 12 of them were male. Median exposure to the drug was 17 month (range 1- 38). After 9 to 36 months from initiation of treatment (median 22 months) 6/15 were thouroughly interviewed about personal history of bleeding events and the following laboratory work was performed: factor VIII level, FVW antigen and activity, platelet function analysis (PFA-100TM) with ADP and epinephrine, and aggregation studies with colagen, ADP and arachidonic acid. Along these tests all patients had blood counts with platelets more than 100 x 10e9/L. RESULTS: 3 out of 15 pts had bleeding events (grade 1 or 2), 2 consisting in spontaneus bruising and 1 in upper grastrointestinal bleeding, in the first weeks of treatment. 4 pts underwent minor invasive procedures with no complications, witholding the drug at least 3 days before and after. 2 pts were on concomitant antiplatelet (1) or anticoagulant (1, LMWH, due to AF) and had no bleeding events. All pts tested (6/6) had normal or slightly elevated leves of F VIII, FVW:Ag and FVW:Ac. 2 pts had abnormal PFA-100TM and abnormal aggregations with any agonist. One case had normal PFA-100 TM while aggregations with colagen and AA were mildly altered. COMMENTS: Our limited experience shows a moderate risk of minor bleedings consisting with a platelet disfunction drug-driven effect. Despite the fact that we have no baseline tests done, alterations in primary hemostasis test, including PFA-100TM and specially aggregometry could be expected early on after exposure to ibrutinib. Disclosures Loscertales: Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead Sciences: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Speakers Bureau. Alegre:Janssen: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees.

Abstract: Elegir entre “aprendizaje electrónico”, “aprendizaje digital” o “aprendizaje virtual” como palabra clave para un artículo científico puede resultar un dilema para un investigador que no conozca la gestión de un tesauro con el cual debe normalizar las palabras clave de su contribución. De momento, la selección de descriptores con mayor o menor acierto es una exigencia que las revistas científicas hacen a sus autores y éstos los consideran un trámite más en la preparación del envío de un artículo. En la actualidad, con la posibilidad de buscar los artículos por texto completo, ¿resulta útil seguir considerándolas?