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Introduction While combination therapy is the standard of care for relapsed/ refractory non-Hodgkin lymphoma (RR-NHL), the choice of combinations for an individual patient is empirical, and response rates remain poor. Here we explore the use of a hybrid experimental/analytic method termed Quadratic Phenotypic Optimization Platform (QPOP), for prediction of optimal drug combinations from limited clinical material. This high-throughput platform identifies optimal drug-combinations on ex-vivo biopsies using an orthogonal array composite design to maximise search space. These features are potentially useful to assess personalized efficacious combinations among a set of drugs with single agent pre-clinical or clinical activity in lymphoma. Methods We performed a prospective cohort study of QPOP analysis in RR-NHL. Participants included RR-NHL patients across two tertiary oncology centres in Singapore, with disease amenable to biopsy or blood/ marrow aspiration, recruited between 1 st November 2017 and 5 th May 2021 - with a median follow up of 24.5 months. CD20, CD3 or CD56 selection was performed to enrich for B, T or NK cells respectively, depending on the specimen type. QPOP drug combination scores were derived from lymphoma samples (approximately 1,000,000 cells/ patient) using a matrix of drugs with known pre-clinical or clinical efficacy against NHL. Results were shared with the treating physician, and off-label QPOP-guided therapy was offered in the absence of standard options. The primary outcomes were feasibility and turnaround time of QPOP analysis. The secondary outcomes were identification of recurrent 2 and 3 drug-combinations, and concordance of QPOP results with clinical responses. Results In this interim analysis period, we recruited 63 patients comprising 36 B-NHL and 27 T/NK-NHL, with a median age of 57 years and median 2 prior lines of treatment. Successful QPOP analysis (Z' score >0.5) was feasible in 56/63 cases with an average turn-around time of 6 (±2.1) days. QPOP predicted frequent sensitivities to Copanlisib- and Venetoclax-based combinations in B-NHL, and Romidepsin-based combinations in T/NK-NHL. Importantly, efficacy of specific combinations was not entirely dependent on single agent dose responses. Greater variability in ex-vivo responses was seen with combinations of targeted therapy and cytotoxic therapy compared with combinations of cytotoxic agents. Clinical responses were evaluable for 29 independent treatments in 26 patients. QPOP had a positive predictive value of 60% and a negative predictive value of 78.6% with an area under the curve of 0.672 (95%CI 0.47-0.87; p=0.12) for partial response or better (n=29, p= 0.06). Complete responses were achieved with novel QPOP derived drug combinations in patients refractory to standard therapy. Examples include Palbociclib-Everolimus for diffuse large B-cell lymphoma (figure 1) and Romidepsin-copanlisib for extra nodal natural killer T-cell lymphoma. Conclusions Prediction of sensitivity to drug-combinations in a clinically applicable time-frame is feasible for RR-NHL cases through QPOP analysis. The relatively small number of patients treated with QPOP directed regimens makes a definitive conclusion on concordance with clinical outcomes difficult at this stage. QPOP was however able to identify novel clinically effective combinations in patients refractory to standard therapy. These data provide the basis for a prospective clinical trial evaluating QPOP based therapy in RR-NHL. Figure 1 Figure 1. Disclosures Chng: Amgen: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Novartis: Honoraria; Abbvie: Honoraria. OffLabel Disclosure: everolimus palbociclib for diffuse large B cell lymphoma and rhomidepsin Bortezomib for extra nodal NK T cell lymphoma

Background Waldenstrom macroglobulinemia (WM) is a rare haematological malignancy characterised by infiltration of the bone marrow by clonal lymphoplasmocytic cells and serum monoclonal IgM gammopathy. Rituximab based chemo-immunotherapy has long been the backbone of WM treatment. Bendamustine rituximab (BR), cyclophosphamide, dexamethasone rituximab (CRD) and bortezomib dexamethasone rituximab (BDR) are currently considered frontline options. The Bruton tyrosine kinase inhibitor (BTKi) ibrutinib in combination with rituximab (IR) has recently shown efficacy in treatment naïve WM and has been approved for use in this setting. With the expanding number of treatment options and absence of randomised trials (RCTs) comparing IR with chemo immunotherapy, there is uncertainty as to the optimal frontline treatment for WM. Methods The aim of this systematic review was to compare the efficacy and safety of rituximab-based chemoimmunotherapy combinations and IR, in treatment naïve WM. Using a pre-specified protocol in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA), MEDLINE, Embase, BIOSIS and Cochrane Library databases were searched for articles published from inception of each database to present. We included trials studying newly diagnosed WM patients treated with rituximab-based chemo-immunotherapy or BTKi based regimens. Primary outcome measures were progression free and overall survival (PFS and OS) while secondary outcomes included response rates and adverse events. A meta-analysis of proportions (expressed as a percentage), with their 95% CI were calculated. Results Of the 753 unique records identified, 8 single arm studies, one phase II non-randomised non inferiority study and 3 Phase III RCTs met the inclusion criteria. The sample size ranged from 23 to 261. PFS at 1- and 2-years were higher in BR(91%, 87%) and IR (93%, 82%), compared to BDR (87.5%, 66.8%) and CRD (82%, 64%) . Combined complete response (CR) and very good partial response (VGPR) rates were also superior with BR (35%) and IR ( 26%) compared to BDR (9%), Bortezomib- Rituximab (8% ) and CRD ( 7%) (Figure 1). The bortezomib bendamustine rituximab ( BBR) regimen was evaluated in only one study but showed an impressive CR/VGPR rate of 47% and a PFS at 3 years of 75%. Bleeding and atrial fibrillation were more common with IR, while neuropathy was more prevalent with bortezomib based regimens. Conclusion We present the first systematic review and meta-analysis evaluating frontline treatment options for WM in the BTKi era. Our findings suggest that bendamustine-based regimens may be superior in terms of depth of response and PFS. Longer follow up of the IR treated patients on the INNOVATE trial is however required to perform a definitive comparison of the regimens. The differential efficacy of these treatments in genomic subtypes of WM (based on MYD88 and CXCR4 mutational status) is an important question to be answered in future trials. While chemo-immunotherapy remains a potent, fixed duration option for newly diagnosed WM, BTKi based regimens are a valid alternative for patients who prefer an oral treatment or who are unfit for cytotoxic therapy. With the expanding number of treatment options for WM, RCTs comparing BTKi/immunotherapy with chemo-immunotherapy regimens are called for. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Background and aims: Angioimmunoblastic T-cell lymphoma (AITL) is currently classified amongst an umbrella group of diagnoses referred to as nodal peripheral T-cell lymphoma (PTCL) with T-follicular helper (TFH) phenotype. In this entity, it is recognized that the presence of atypical B-cell blasts mimicking Hodgkin-Reed-Sternberg cells may lead to misdiagnosis as Hodgkin lymphoma (HL), resulting in suboptimal management and poorer outcomes. This diagnostic complexity has been acknowledged by the World Health Organization classification of lymphoid neoplasms. In this study, we aim to investigate the clinical features and outcomes of such cases of diagnostic ambiguity (HL/PTCL). Methods: A total of 379 patients from the Singapore Lymphoma Study database across three tertiary cancer centers (National Cancer Centre Singapore, Singapore General Hospital, National University Cancer Institute) were included in this study, including those diagnosed with AITL (n=169), HL (n=178) and HL/PTCL (n=32). Median follow-up was 47.5 months. Relevant demographical and clinical characteristics were collected. Survival analyses were performed using the Kaplan-Meier method. Results: The 32 patients with HL/PTCL were identified from three distinct clinical scenarios. In the first group (n=18), an initial histological diagnosis of HL was revised upon independent pathological re-assessment following a second opinion consultation (revised diagnoses to AITL, n=10; PTCL-TFH, n=7; PTCL-NOS, n=1). In the second group (n=11), the histological diagnoses were different at diagnosis and at relapse (mostly HL relapsed as AITL/PTCL-TFH, n=9). The third group consisted of patients with synchronous or composite features of both HL and AITL/PTCL at diagnosis (n=3). In the overall cohort, most were male (62.5%), and the majority had excellent performance status with ECOG 0-1 (96.9%). The median age was 45 years (range, 20 to 77), which is older than the HL cohort (28 years, p=0.0012) but younger than the AITL cohort (62 years, p=0.0005). In terms of disease staging, most were Ann Arbor stage 3-4 (62.5%), which is comparable to the AITL cohort (78.3%), but significantly more advanced than the HL cohort (32%, p=0.001). HL/PTCL represented a group with worse prognostic risk scores by IPI as compared to HL (p=0.0038), but better as compared to AITL (p=0.0418). Accordingly, the median overall survival was 8.4 years for HL/PTCL, compared to 5.5 years (AITL) and not reached (HL) (logrank p Conclusion: We describe a significant and clinically distinct group of HL and AITL/PTCL-TFH cases which are challenging to diagnose. Further studies on the molecular characteristics of this ambiguous disease entity may be required to resolve the diagnostic difficulties. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Introduction There is currently no standard of care for the upfront management of patients with mature T cell non-Hodgkin lymphomas (T-NHL). The role of anthracyclines in the treatment of T-NHL remains unclear and is also associated with significant toxicity. CEPP (cyclophosphamide, etoposide, procarbazine, and prednisone), a non-anthracycline regimen, is an effective salvage regimen for relapsed/refractory NHL and has shown a favourable toxicity profile. Since 2005, CEPP has been used in Singapore in the upfront treatment of T-NHL patients either with a contraindication to anthracyclines or at physicians' discretion. Our study aimed to assess the efficacy of CEPP in the upfront treatment of T-NHL. Methods A retrospective study of all patients with newly diagnosed T-NHL treated with CEPP with curative intent from 2005-2021 was undertaken across 2 national cancer centers in Singapore. Outcomes of this population was also compared with a 1:1 control group treated with CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone) in the same time period, and matched for age, T-NHL subtype, clinical stage and international prognostic index (IPI). Patient demographics, disease characteristics and clinical outcomes (progression free survival, PFS and overall survival, OS) were evaluated. None of the patients had upfront autologous transplantation. Results We identified 34 patients treated with CEPP who met the inclusion criteria. Clinical characteristics were as follows: Median age was 71 (range 39-85), 24 (71%) were male, 26 (76%) had advanced disease (Stage III-IV) and 21 (62%) had a high intermediate or high risk IPI ( IPI 3, 14 (41%) and IPI 4-5, 21 (21%)). The most common T-NHL subtypes were peripheral T-NHL (PTCL-NOS) not otherwise specified, 11 (32%) as well as angioimmunoblastic T cell lymphoma (AITL), 16 (47%). At a median follow up of 20 months (range 2-197months), the median PFS and OS were 17.6mths and 37.2mths respectively for the CEPP group. 15/34 (44%) CEPP patients have died (8 with lymphoma, 2 from treatment toxicity and 5 from unrelated causes). In the matched control comparison, the 5yr PFS and OS were both similar for patients treated with CEPP compared to patients in the CHOP control group, PFS 30% vs 32%, p= 0.43 and OS 47% vs 52%, p = 0.32, respectively (Figure 1) Conclusion Our findings show that CEPP is a well-tolerated regimen which can cure a proportion of patients with T-NHL even without autologous transplantation consolidation. Outcome of these patients do not seem to be significantly different compared to a similar population treated with standard CHOP. This study supports CEPP as a tolerable treatment option for selected patients who cannot tolerate anthracyclines and as an alternative to CHOP regimen for older patients who are not planned for ASCT. Figure 1 Figure 1. Disclosures Jeyasekharan: Turbine Ltd: Consultancy; Janssen: Consultancy, Research Funding; AstraZeneca: Consultancy, Research Funding; Perkin Elmer: Other: travel funding ; MSD: Consultancy.

Introduction: There is currently no consensus on the optimal frontline therapy for patients with T cell Non-Hodgkin lymphomas (T-NHL). Consolidative autologous stem cell transplant (ASCT) is frequently offered to the patients with chemosensitive disease based on retrospective and prospective studies showing improved progression-free survival (PFS) when compared with historical controls getting chemotherapy alone. However, it remains unclear whether there is a good risk subset of patients who achieve first complete remission (CR1) following induction chemotherapy and who might not benefit from upfront ASCT. To date, no randomized control trials (RCTs) exist and available data is conflicting. We perform a systematic review/meta-analysis of the published literature to address this question. Methods A comprehensive, systematic search (from database inception - 9/2019) of MEDLINE/PubMed, EMBASE and Cochrane databases was performed. PRISMA and Meta-Analysis Of Observational Studies in Epidemiology (MOOSE) guidelines were followed. Studies were selected from a total of 2656, screened based on predefined inclusion/exclusion criteria, and were critically appraised for outcomes of interest [progression free survival (PFS) and overall survival (OS)]. Quality of studies was assessed using Newcastle-Ottawa Scale. Hazard ratios (HRs) and corresponding 95% Cis were calculated, and the meta-analysis was performed using the random-effects model. Test for heterogeneity was performed using I2 statistic. Results Of 2656 unique records, 13 studies (prospective = 3; retrospective = 10) were selected. In 8 studies, upfront ASCT was compared to NO ASCT in patients in first complete remission (CR1), while in 5, comparison was with patients achieving either PR1 (first partial remission) or CR1. 11 (of 13) studies reported PFS. Median follow-up in these studies ranged from 22 months to 7.8 years. Results from the meta-analysis showed that T-NHL patients who underwent ASCT had an improved 5-year PFS compared to those with NO ASCT (HR 1.62, 95% confidence interval (CI) 1.22 to 2.15, I² = 38%) (Figure 1). However, no benefit was observed in 5-year OS when ASCT was compared to NO ASCT (HR 1.32, 95% CI 0.82 to 2.12, I2 = 83%) (Figure 2). A sensitivity analysis including only studies with patients transplanted in CR1 showed similar findings, with a 5-year PFS (HR 1.54, 95% confidence interval (CI) 1.01 to 2.34, I² = 38%) and 5-yr OS (HR 1.11, 95% CI 0.41 to 3.02, I2 = 90%) when compared to No ASCT. Conclusions In the absence of RCTs, the results of this systematic review/meta-analysis represents the best evidence supporting long term PFS benefits of upfront ASCT consolidation in patients with T-NHL in CR1 or CR1/PR1 after frontline chemotherapy. Disclosures No relevant conflicts of interest to declare.

Introduction High-grade B-cell lymphomas are a subgroup of lymphomas characterized by high-grade morphological appearances and the presence of rearrangements in MYC in addition to BCL2 and/or BCL6 (HGBL-DH/TH) or in the absence of cytogenetic changes, HGBL-NOS, previously described as B-cell lymphoma unclassifiable with features intermediate between diffuse large B-cell lymphoma and classical Burkitt's lymphoma (BCLU). These entities have been shown to have poorer outcomes from conventional treatment compared with diffuse large B cell lymphomas (DLBCL) not otherwise specified. One feature contributing to the poor prognosis of DHL is increased risk of central nervous system (CNS) involvement. Intensive chemotherapy regimens which include CNS prophylaxis may improve PFS in HGBL compared with R-CHOP-like therapy. Methods We conducted an international, multi-center retrospective analysis of HGBL-DH/TH/NOS and BCLU. The association between baseline clinical and histopathological characteristics and clinical outcome was assessed by Cox proportional hazards model, and variables with P Results 57 patients were included - 20 patients with MYC/BCL2 rearrangements, 6 patients with MYC/BCL6 rearrangements, 13 with MYC/BCL2/BCL6 rearrangements, 16 with the WHO 2008 BCLU classification and 2 with HGBL-NOS classification. 16 (28%) patients had evidence of transformation from antecedent or synchronously diagnosed indolent lymphoma. The median age at diagnosis was 63 years (range 39-86), with 30 (53%) male and median year of diagnosis was 2015 (range 2011 - 2017). The majority of patients were Stage III/IV [n=42, 74%] and ECOG ≤ 1 [n=44, 77%]. 40 patients (70%) had raised LDH at diagnosis; in 15 (26%) LDH was ≥3x ULN. Bone marrow involvement with high-grade lymphoma and extranodal involvement (excluding bone marrow) were present in 9 (16%) and 34 (60%) patients respectively. The median number of extranodal sites of involvement was 1 (range 0-10). Of 32 patients (56%) who underwent CNS staging at diagnosis, 2 (6%) had CNS involvement at baseline- one diagnosed with CSF cytology, and the other by combined modalities (CSF flow cytometry, cytology and MRI). R-CHOP was the most common initial (49%) and ongoing (39%) induction chemotherapy regimen, followed by dose-adjusted EPOCH (32%), R-HyperCVAD and R-CODOX-M/IVAC (7% each) and other regimens (9%). A predominance of patients [n=33, 58%] received a form of CNS directed treatment- 8 (14%) as a standard component of the chosen induction regimen, and 25 (44%) as an addition to induction treatment (intrathecal [n=18, 32%], systemic therapy [n=2, 4%] or both [n=5, 9%]). At a median follow-up of 25 months (range 5-67), the 2 year PFS and OS was 68% (95% CI: 50-81%) and 74% (95% CI: 55-85%) respectively for HGBL-DH/TH and 67% (95% CI: 40-83%) and 72% (95% CI: 46-87%) for BCLU/HGBL-NOS (Figure 1). Outcomes between the R-CHOP and intensive chemotherapy regimens were similar. At 2 years PFS was 70% (95% CI: 44-86%) vs 73% (95% CI: 52-86%), and OS was 79% (95% CI: 52-92%) vs 76% (95% CI: 56-89%). Two patients experienced CNS progression- one in a patient with BCLU and documented CNS disease at diagnosis, and another as a presentation of CNS relapse in a patient with HGBL-TH without evidence of CNS disease at diagnosis who did not receive specific CNS prophylaxis. Raised LDH was adversely prognostic for PFS in entire cohort and ECOG >2 was adversely prognostic for OS in the BCLU/HGBL-NOS group. Among patients who achieved a complete response at end of treatment, the 2 year PFS and OS was 96% (95% CI: 75-99%). In patients who had non-complete response (PD, SD, PR) the 2 year PFS and OS was 29% (95% CI: 13-48%) and 42% (95% CI: 22-62%) respectively. Among 23 patients (40%) with Deauville scores reported, those with Deauville score of 1-3 had a 2 year PFS and OS of 100%, with no events amongst 17 patients. Conclusion Within the limits of a retrospective analysis, outcomes of HGBL-DH/TH and HGBL-NOS/BCLU were similar. Rates of CNS involvement at diagnosis and on relapse were comparable with other retrospective series. Negative end of treatment PET-CT (DS 1-3) identifies a subset of patients with favorable prognosis. Disclosures Jeyasekharan: AstraZeneca: Other: Collaboration; Merck Sharp & Dohme: Honoraria; Janssen: Research Funding; PerkinElmer: Other: Collaboration. Bishton:Gilead: Research Funding; Abbvie: Research Funding; Roche: Research Funding; Takeda: Other: travel support to ASH.

BACKGROUND/OBJECTIVE: DLBCL is a heterogeneous disease which on gene expression profiling studies (GEP) can be divided into 2 distinct subtypes, germinal center (GCB) as well as activated B cell subtype (non GCB) based on the cell-of-origin. Immunochemistry (IHC) based algorithms have been shown to have good concordance with GEP for COO classification. While Western data suggests that GCB-subtypes are associated with improved outcomes, there has been limited and conflicting data on the prognostic significance of COO amongst Asian patients. The prevalence and prognostic significance of other prognostic markers such as MYC overexpression or translocation amongst DLBCL Asian patients also remains unclear. Our study aimed to evaluate i) the prevalence of MYC translocation and overexpression, as well as COO subgroups of DLBCL in a cohort of Singaporean patients, and ii) the prognostic impact of these factors in comparison with International Prognostic Index (IPI) score and other standard prognostic markers. METHODS: A single-center retrospective analysis of 384 consecutive DLBCL patients diagnosed 2013 - 2018 was performed. Hans criteria was used to assign COO. (Prior validation studies from the hospital's pathology laboratory had confirmed concordance between Hans algorithm and GEP of 75 %.) Majority of the patients received R-CHOP (N =228) or R-EPOCH (N =47) chemotherapy RESULTS: The median age of the cases was 61 years (range 18-88), 223 were female and the majority had stage 3-4 disease (62%). Of the 297 cases with IHC data for COO, 120 (40%) were GCB subtype and 177 cases (60%) were non-GCB. MYC was overexpressed in 75% of cases (165/220) tested, while MYC FISH was positive in 23% of cases (28/122) tested. 10 of the 28 patients with MYC FISH positive were treated with R-EPOCH chemotherapy. With a median follow up of 1.2 years (0.1-5.3 years), the projected 5-year OS and PFS for the entire cohort was 69.5% and 65.6% respectively. Amongst baseline clincopathologic characteristics, only age, IPI and disease stage was associated with improved OS on both univariate and multivariate analysis. Age, IPI and disease stage was associated with PFS in univariate analysis but only IPI remained significant (p CONCLUSION: In this Southeast Asian DLBCL cohort, we confirmed the prognostic significance of the IPI score for both PFS and OS. GCB subtype of DLBCL comprised 40% of all DLBCL cases. COO based on Hans criteria had no prognostic significance on PFS or OS. This is in contrast to Western series where GCB subtypes identified by IHC-algorithms are associated with better prognosis. Disclosures Jeyasekharan: PerkinElmer: Other: Collaboration; Merck Sharp & Dohme: Honoraria; Janssen: Research Funding; AstraZeneca: Other: Collaboration.

Background/Objective: Marginal zone B-cell lymphomas (MZL) represent a heterogeneous group of indolent lymphomas, comprising of MALT lymphomas, nodal MZL and splenic MZL. Currently, there has been no widely accepted prognostic indices for these lymphomas. Recently, the International Extranodal Lymphoma Study Group (IELSG) developed a novel simplified MALT prognostic index (MALT-IPI)1, which was subsequently validated by a western cohort of MALT cases. To date, there has not been an assessment of the applicability of this score in other subtypes of MZL or in the Asian population, where geographic and ethnical differences may influence disease epidemiology and outcomes. Our study aimed to 1) Evaluate clinical characteristics and survival outcomes for a large cohort of Southeast Asian patients with MZL who were diagnosed between 1993 - 2018 and ii) Assess the prognostic significance of the MALT-IPI for this patient cohort. Patients and Methods: We retrospectively studied 286 consecutive patients with newly diagnosed MZL treated between 1993 to 2016 at 2 tertiary cancer centres in Singapore. Data on clinical parameters, treatments, response, and survival were evaluated. In addition, all patients with available data were classified according to the MALT-IPI (N =236, including MALT lymphomas N= 190 and nodal/splenic MZL, N= 46) and the prognostic significance of this score was evaluated. Results: Among 286 patients with MZL, 230 patients (80%) had MALT lymphomas, 35 (12%) had nodal MZL and 21 (7%) had splenic MZL. The median age was 60 years (range 15- 94), 49% of the patients were male and 183 patients (64%) had Stage I-II disease. The majority of the patients were managed by either radiotherapy (N= 77, 27%), chemo and/or immunotherapy (N= 76, 27%), watchful waiting (N-= 46, 16%) or antibiotics (N= 33, 11.5%).With a median follow-up of 46 mths (range 1 - 266 mths) for all patients, the 5 yr-PFS for the cohort was 59.8 %. Progression free survival was significantly better for the MALT subgroups compared to the nodal and splenic MZL subgroups ( 5 yr PFS of 63.6 vs 49.7 % vs 30.5 % respectively, p=0.002). The 5-yr OS was excellent at 86.7% and there were no differences between the MALT, nodal MZL and splenic MZL cohorts (5-yr PFS 87.1 vs 85.3% vs 86.4, p=0.667). Age, ECOG status and elevated LDH were prognostic for PFS on univariate analysis but none has significant impact on multivariate analysis. No other baseline clinical characteristic (including gender and disease stage) was significantly associated with PFS. Age and ECOG was significantly associated with OS on both univariate and multivariate analysis. In our cohort, the MALT-IPI was a significant prognostic marker with ability to discriminate different prognostic groups with respect to PFS and OS. The 5-year progression-free survival rate for patients who had MALT-IPI scores of 0, 1 or 2-3 were 78%, 58% and 42%, respectively (p Conclusion We demonstrated the prognostic applicability of the MALT-IPI to identify patients at risks of progression or death, in a large cohort of Asian patients with MZL. Patients with high risk MALT-IPI appear to be associated with poor outcomes and may be candidates for novel treatment approaches. Disclosures Jeyasekharan: AstraZeneca: Other: Collaboration; Merck Sharp & Dohme: Honoraria; PerkinElmer: Other: Collaboration; Janssen: Research Funding. Goh:Johnson & Johnson: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Astellas: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Sanofi-Aventis: Consultancy, Honoraria; Bristol-Myers-Squibb: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria.