ALBERT

Description: Abstract 3056 Introduction: Multiple myeloma (MM) is clinically heterogeneous and risk stratification is vital for prognostication and informing treatment decisions. As bortezomib is able to overcome several adverse features of MM, it has been incorporated into the induction algorithms of high-risk MM. We evaluate the survival data of MM patients managed in a single institution, overall, and with respect to treatment eras before (era 1) and after (era 2) the incorporation of bortezomib as frontline therapy for high-risk MM. Methods: From a comprehensive MM registry maintained in a tertiary institution, we study the survival data of 304 consecutive and previously untreated MM patients managed at our institution from 2000 to 2009. For induction therapy, transplant-eligible patients received. VAD chemotherapy from 2000 to 2004, and thalidomide/dexamethasone (thal/dex) combination from 2004 to 2009. Transplant-ineligible patients received VAD chemotherapy, thal/dex or melphalan/prednisolone (MP) combination from 2001 to 2004, and thal/dex or MP/thalidomide combination from 2004 to 2009. Patients 〈 65 years were eligible for high-dose therapy with autologous stem cell transplant (HDT/ASCT). Bortezomib became available for treatment of relapsed disease from 2004 and was incorporated into induction therapy in selected patients with high-risk MM from 2006. High-risk MM is defined by presence any adverse factors including stage III on the International Staging System (ISS), deletion 13, hypodiploidy, pseudo-diploidy or near-tetraploidy on metaphase karyotyping, or presence of deletion 17p, t(4;14) or t(14;16) on interphase florescence in-situ hybridization (FISH). As FISH was only available from 2004, the results of FISH will not be included in the survival analysis. Patient and disease characteristics, and survival data were evaluated overall, and with respect to treatment eras. Disease response was assessed by the IMWG criteria after induction treatment and after HDT/ASCT for transplant ineligible and eligible patients respectively. We applied multivariate Cox's regression modeling to determine what baseline parameters, along with the eventual induction response, significantly affected the OS in the respective eras. Results: The median age of all patients was 62 years. Overall, 35%, 40% and 25% of patients presented with ISS stages I, II and III respectively. Conventional karyotyping detected abnormalities in 49% (del 13 [17%], hypodiploidy [18%], hyperdiploidy [22%], pseudodiploidy [7%] and near tetradiploidy [2%]) of patients. Overall, the ISS, conventional cytogenetics, age (≤ or 〉 60 years), the presenting platelet count (≤ or 〉 140 × 109/L) and the induction response attained were discriminating of the overall survival (OS) (median= 5.2 yrs) on univariate analyses. Patients and disease characteristic and number of patients undergoing HDT/ASCT were comparable between the 2 eras. 33% of patients in era 1(N=182) were exposed to bortezomib predominantly in the relapse setting, while 52% (41% upfront, 59% during relapse) of patients were exposed to bortezomib (N=123) in era 2. Number of patients attaining ≥ very good partial response (VGPR) were significantly higher in era 2 compared with era 1 (48% vs 26%, p

Description: Background: Multiple myeloma is a heterogeneous disease with certain genetic features associated with worse outcomes. The benefit of Bortezomib for high risk genetic patient subgroups remains unclear in an Asian population. We performed a retrospective analysis to compare bortezomib-based induction versus thalidomide-based induction in Asian patients who were treated with upfront autologous transplant. Methods: We retrospectively analyzed outcomes of 240 patients who received autologous transplant in two centers in Singapore (n=167) and one center in Korea (n=73) after bortezomib-based (n=120) versus thalidomide-based induction (n=120) between 2006 and 2014. Patients were staged according to International Staging System (ISS), and responses were defined according to International Myeloma Working Group criteria. Early relapse was defined as relapse within 12 months post-transplant. High risk cytogenetics included the presence of 17p13 deletion, t(14;16), or t(4;14) by FISH. Results: Baseline characteristics (age, gender, ISS, cytogenetics) were not significantly different between groups receiving bortezomib versus thalidomide induction. Bortezomib induction was associated with improved rates of complete response (CR) post-induction (40% vs 25%, p=0.013) and post-transplant (52% vs 48%, p=0.038). Median overall survival (OS) was prolonged with bortezomib (53 months vs 27 months, p=0.027). Multivariate analysis adjusted for baseline characteristics showed bortezomib reduced the risk of early relapse (HR 0.23, 95% CI 0.09-0.57, p=0.001), and improved overall survival (OS) (HR 0.2, 95% CI 041-0.93, p=0.021). Factors independently associated with poorer OS were high risk cytogenetics (HR 1.77, p=0.011), failure to achieve very good partial response (VGPR) or better post-induction (HR 1.70, p=0.005), early relapse (HR 6.20, p

Description: Introduction: Hemophagocytic syndrome (HPS) is a clinicopathologic entity characterized by fever, hepatosplenomegaly, cytopenia and liver dysfunction due to dysregulated activation of non-neoplastic histiocytes. It is associated with a myriad of different causes, commonly resulting in an unfavourable outcome. Data pertaining to its approach is scarce. The link with various infectious agents results in geographical differences in the incidence and etiology. Advances in immunophenotyping has allowed it be better delineated. We report the clinical spectrum and outcome of 49 cases of HPS in an adult Asian population in a single institution over 5 years. Gaining a better insight into its etiology will help us adopt a better management approach. Method: This is a retrospective analysis. Patients with findings of hemophagocytosis on bone marrow morphology were identified and clinical records of such patients were reviewed. Only patients who fulfil the criteria of having HPS were included. Results: Of the 49 cases, 32 (65%) were due to malignant lymphoproliferative diseases (LPD), of which 22 (70%) were of NK/T and 10 (30%) were of B-cell lineages. The former group consisted peripheral T-cell lymphoma (PTCL) (n=10), hepatosplenic γδ TCL(n=2), anaplastic large TCL(n=2) and NK-cell LPD(n=8). Amongst cases of NK LPD, 3 started as extranodal nasal type, while 5 presented as aggressive NK-cell leukemia. Common to both the PTCL and NK-cell LPD was the demonstration of EBV involvement by EBER ISH or PCR for EBV DNA and the absence of serological evidence of an active EBV infection. Tumour masses were however not striking. Bone marrow, skin and liver biopsies appear to be of great importance for diagnosis. The distinct entity of fulminant EBV associated NK/T LPD, which typically affected young and seemingly immunocompetent patients was seen in 10 patients. Mortality was uniform, with MS of only 29 days. An immunomodulatory approach prior to ablative chemo seemed to prolong the survival. Cases of B-cell LPD (7 DLBCL, 2 lymphoplasmacytoid lymphoma and 1 MALT lymphoma) with HPS had a less ominous course. Advanced stages at presentation was peculiar. Other malignancies included metastaic gastric ca (n=1)and acute leukemia (n=1). Non-malignant causes of HPS (30%) included disseminated TB (n=5), SLE (n=3), HIV (n=2), bacterial (n=1) and dengue fever (n=1). Despite similar presenting features, the prognosis of non-malignant causes of HPS was good once appropriate treatment was instituted. Two patients with disseminated TB who did not receive anti-TB treatment due to a delay in diagnosis succumbed to HPS. Etiological cause of HPS could not be elucidated in only 3. Discussion: The clinical spectrum is broad. Vigorous search for an underlying etiology is crucial. Infectious disease screening have to be guided by epidemiological data. Benign viral causes are not common compared to western data. Delay in diagnosis may compromise the outcome of a treatable infection. EBV-associated NK/T LPD accounts for a disproportionate number of cases unique to the Asian perspective and prognosis remains dismal. An important pitfall in their diagnosis is the lack of serological evidence of EBV, possibly implying a lack of humoral response to acute EBV infection. Reasons for the epidemiologic predisposition remain elusive, but one may speculate that high prevalence of EBV infection, together with a yet unidentified defect in immune response to EBV may play a role. Immunomodulation has a role in controlling the cytokine storm which may have a more detrimental effect than the LPD initially.

Description: Background Relapsed/refractory PTCL and NKL after conventional chemotherapy carry a poor prognosis and there is currently no proven salvage treatment available. Numerous preclinical studies have demonstrated synergistic interactions between proteasome and histone deacetylase (HDAC) inhibitors. PAN inhibits the aggresome pathway of protein degradation, which is upregulated when the proteasome pathway is inhibited by BTZ. Primary end point of this phase II multi-center open-label clinical study (NCT00901147) is the objective response rate (ORR) according to the Revised Response Criteria (Cheson 2007) among eligible patients (pts) treated with this novel combination of BTZ and PAN. Secondary end points include the evaluation of the progression-free survival (PFS) and the assessment of the safety and tolerability of the combination. We report the final clinical results of our study exploring this novel combination. Methods Pts with histologically confirmed PTCL or NKL who failed or were refractory to 1 or more prior systemic therapy, and had measurable disease and ECOG performance status 0–2 were eligible. Pts were accrued according to a 2-stage Gehan design. Pts receive thrice weekly oral PAN (20 mg) and twice weekly BTZ (IV 1.3 mg/m2), both for 2 of 3 weeks for up to 8 cycles. CT scanning and/or FDG-PET were performed after every two cycles. Results: Among 25 pts enrolled, histologies included: angioimmunoblastic T-cell lymphoma (AITL) n=8, PTCL (unspecified) n=11, Anaplastic large cell lymphoma, ALK+ and ALK- n=1 and 2 respectively, NKL, nasal type n=2 and subcutaneous panniculitis-like T-cell lymphoma n=1. The median age was 59 (35-79) years, and 64% were male. Outcomes are available on 23 patients as 2 patients withdrew consent before any response assessment could be made. The ORR (CR+PR) was 43% (10/23) with 22% (5/23) attaining a CR. Median time to response was 6 weeks. Five pts (22%) had stable disease while 8 pts developed progressive disease (35%) while on study. Pts received a median of 2 prior therapies (range 1-4); 28% had prior autologous stem cell transplantation (SCT). Common treatment-related grade 3/4 adverse events included thrombocytopenia (68%), neutropenia (36%), diarrhoea (28%) and asthenia/fatigue (16%). Peripheral neuropathy of any grade was observed in 40%. 5 pts successfully underwent subsequent allogeneic SCT. Updated survival analysis will be presented. Conclusions The study regimen is generally well tolerated and shows encouraging activity across different T/NK-cell lymphomas. The novel combination could successfully serve as a bridge to allogeneic SCT for many transplant-eligible patients who have failed conventional chemotherapy. These results form the basis for further validation studies on proteasome and HDAC inhibition in PTCL or NKL. Ongoing correlative studies are designed to determine if the study regimen is more active in diseases with up-regulation of NF-kappa B activity or transcription factors/ co-regulators known to be modified by acetylation. Disclosures Goh: Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Jannsen Pharmaceuticals: Honoraria, Research Funding, Speakers Bureau; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead Sciences: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees. Kim:Novartis, Celgene, Takeda: Research Funding. Tan:JANSEN: Honoraria, Research Funding; NOVARTIS: Research Funding.

Description: Abstract 5035 Background: The incidence of multiple myeloma (MM) is known to be variable according to ethnicity. However the difference of clinical characteristics between ethnic groups is not well-defined. In Asian countries the incidence of MM has been lower compared with Western countries. However, there are growing evidences that MM is increasing very rapidly in this region. Until now, only few data of Asian patients has been reported. Asian myeloma network (AMN) decided to analyze the first multinational project to explore clinical characteristics of Asian MM patients and clinical practice performed in Asian countries. Methods: Data were collected from 22 centers from 7 countries and regions were collected retrospectively. Clinical characteristics of 3377 symptomatic MM patients at diagnosis were described. Overall survival (OS) and prognostic factors were analyzed for 3324 patients who have survival data. Results: Clinical and genetic characteristics were summarized at table 1. Median OS was 47 months (95% CI 48. 0–60. 0). Patients who were diagnosed before 2000 were shorter survival. Transplantation was performed to 607 patients with better survival (84 vs 40 months, p

Description: Abstract 2658 Background: Peripheral T-cell lymphomas (PTCL) carry a poorer prognosis compared to their B-cell counterparts and the molecular pathogenesis of PTCL is still largely unknown. The aims of this study are to characterize the molecular signatures and identify signaling pathways involved in the different subsets of PTCL and NKTCL. Materials and Methods: RNA was extracted from tumors of 60 patients with newly diagnosed PTCL and NKTCL: 21 with angioimmunoblastic T-cell lymphoma (AITL), 12 anaplastic large-cell lymphoma (ALCL), 15 peripheral T-cell lymphoma not-otherwise-specified (PTCL-NOS) and 12 with natural-killer T-cell lymphoma (NKTCL). Comparisons were made using published gene expression data files of normal T and NK T-cells. Gene expression profiling was performed using the Affymetrix HG-U133 Plus 2.0 GeneChip platform. Results: The Affymetrix expression profiling distinguishes the 48 PTCL samples from normal T-cell controls (p

Description: Background: Recent data from retrospective and prospective studies indicate an improvement in the overall survival (OS) of follicular lymphoma (FL) patients (pt). We sought to evaluate survival data in FL pt managed at our institution and to analyze their presenting features, management and disease course. Methods: Previously untreated FL (grades 1 and 2) pt referred from 1960–2003 and followed at Stanford were identified from the Lymphoma Database for this retrospective study. Data were reviewed for quality and consistency of coding for histology (pathology reviewed at Stanford) and treatment courses. Four eras were defined by date of diagnosis 1 (1960–75, n=180); 2 (1976–86, n=426); 3 (1987–96, n=471); and 4 (1997–2003, n=257). Patient (age, gender) and disease (stage, histology) characteristics, management (time from diagnosis to referral, time to first treatment, courses/types of treatment), and outcomes (progression-free survival [PFS], OS, transformation) were evaluated, overall and with respect to era. Results: The OS for the 1334 FL pt in the dataset was 12.6 years (yr). Age (median = 49 yr), gender (54% male) and stage (83% III-IV) did not differ across the eras. Median OS improved from 11.2 yr [95% CI 10.2,12.1] in eras 1 and 2 (1960–86) to 18.4 yr [95% CI 14.5,22.4] in eras 3 and 4 (1986–2003), p

Description: 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