scholarly journals Frontline Therapy with Bendamustine-Rituximab (BR) in Patients with Treatment-Naïve Waldenstrom's Macroglobulinemia Confers Similar Long-Term Outcomes to R-CVP in a Real-World Setting: A Population-Based Analysis

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1353-1353
Author(s):  
Jowon Laura Kim ◽  
Alina S. Gerrie ◽  
Kerry J. Savage ◽  
Diego Villa ◽  
David W. Scott ◽  
...  
Keyword(s):  
Gene Expression ◽  
Clinical Trial ◽  
Gene Expression Profiling ◽  
Systemic Therapy ◽  
Expression Profiling ◽  
Research Funding ◽  
Population Based ◽  
Early Progression ◽  
Treatment Naïve

Abstract Background: Waldenström macroglobulinemia (WM) is a rare, indolent B-cell lymphoproliferative disorder. After the STiL-1 trial (Rummel MJ. Lancet. 2013;381(9873):1203-1210) demonstrated significant benefit in a subgroup analysis as well as reduced toxicity using bendamustine and rituximab (BR) compared to R-CHOP (N=41 enrolled WM patients), BR became the preferred immunochemotherapy (IC) regimen for all patients with symptomatic treatment naïve (TN) WM in British Columbia (BC) since 2014. Prior to the introduction of BR, the combination of rituximab, cyclophosphamide, vincristine, and prednisone (RCVP), was the standard of care in BC for this population since 2004, given its widespread use across a broad range of indolent B-cell lymphomas. We report a population-based analysis evaluating outcomes in TN-WM patients comparing BR with RCVP. Methods: The BC Cancer Centre for Lymphoid Cancer Database was used to identify TN-WM patients treated with BR or RCVP as their first systemic therapy between August 1, 2004 - August 1, 2020. A period of observation but no prior to systemic therapy was permitted. All patients had clinicopathologically confirmed lymphoplasmacytic lymphoma and measurable monoclonal IgM. Event-free survival (EFS) was defined as time from start of IC to progression, relapse, initiation of alternative therapy, histologic transformation, or death due to any cause. Early progression (POD24) was defined as relapse or progression, death from lymphoma, or treatment toxicity within 24 months of initiation of systemic therapy. Outcomes were compared with a historical cohort of patients treated with frontline RCVP. Responding patients were eligible to receive maintenance rituximab (MR) every 3 months for 2 years since 2006; however this was discontinued in 2020 when a subgroup analysis of the MAINTAIN trial (Rummel MJ. Blood 2019; 134 (Supplement_1): 343), showed a lack of PFS benefit after BR, coupled with safety and vaccine response concerns during the COVID-19 pandemic. Results: A total of 111 patients with WM were identified; 57 treated with BR, 54 treated with RCVP. Median age was 69 years (range 33-89) and baseline characteristics (Table 1), were well-balanced. A higher proportion of RCVP-treated patients received >4 cycles of chemotherapy (81% vs 65%, p=0.049). After IC, 75 (68%) received MR, with 36 (63%) and 39 (72%) in the BR and RCVP groups respectively (p=0.3). Median follow-up from diagnosis for all living patients was 5.9 years (range 0.8-19.2), with median 4.4y vs 9.8y for BR and RCVP respectively. EFS estimates at 4-years achieved with BR were 57% (95% CI 40-71%) compared to RCVP 60% (95% CI 45-72%), p=0.5 (Figure 1). Median EFS was established for RCVP due to longer duration of follow up at 6.3 years (95% CI 3.6-11.8y). Overall survival (OS) estimates at 4-years were 74% (95% CI 57-85%) and 81% (95% CI 67-89%) for BR and RCVP patients respectively, p=0.6. Worse performance status (≥2) was the only pre-treatment factor identified as significant for inferior EFS. A sub-analysis limited to patients that received >4 cycles of IC also showed no clear difference in outcomes between BR and RCVP. Median time to transformation was 6.5y (5.5-13y), with only 3 late biopsy-proven events. Early progression (POD24) has occurred in 19 (18%) patients, with inferior survival observed in patients that had an early event compared with a reference cohort (2-years event free), however this did not reach statistical significance (p=0.3) (Figure 1). Conclusion: This population-based analysis of TN-WM patients treated with upfront IC confirms the excellent outcomes that can be achieved with a finite course of therapy. In contrast to prior studies, similar outcomes were observed with RCVP and BR. Further, regardless of front-line therapy, POD24 may be associated with inferior outcome but larger studies are needed. To our knowledge, this study is the first to make a direct comparison between BR and RCVP, and one of the largest restricted to IC-treated TN-WM. This data supports RCVP as a viable option, and should serve to inform clinicians, patients, and policy makers in decision-making when considering upfront therapeutic options, and when considering indefinite alternative regimens such as BTK inhibitors. Figure 1 Figure 1. Disclosures Gerrie: AbbVie: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Astrazeneca: Honoraria, Research Funding; Sandoz: Honoraria; Roche: Research Funding. Savage: Servier: Consultancy, Honoraria; Astra-Zeneca: Consultancy, Honoraria; BMS: Consultancy, Honoraria, Other: Institutional clinical trial funding; Seattle Genetics: Consultancy, Honoraria; Merck: Consultancy, Honoraria, Other: Institutional clinical trial funding; Takeda: Other: Institutional clinical trial funding; AbbVie: Consultancy, Honoraria; Roche: Research Funding; Beigene: Other: Institutional clinical trial funding; Genentech: Research Funding. Villa: Roche: Honoraria; Janssen: Honoraria; Lundbeck: Honoraria; Celgene: Honoraria; Seattle Genetics: Honoraria; AbbVie: Honoraria; AstraZeneca: Honoraria; Gilead: Honoraria; NanoString Technologies: Honoraria. Scott: BC Cancer: Patents & Royalties: Patent describing assigning DLBCL COO by gene expression profiling--licensed to NanoString Technologies. Patent describing measuring the proliferation signature in MCL using gene expression profiling. ; Abbvie: Consultancy; Janssen: Consultancy, Research Funding; AstraZeneca: Consultancy; Rich/Genentech: Research Funding; Celgene: Consultancy; Incyte: Consultancy; NanoString Technologies: Patents & Royalties: Patent describing measuring the proliferation signature in MCL using gene expression profiling.. Craig: Bayer: Consultancy. Slack: Seagen: Consultancy, Honoraria. Sehn: Debiopharm: Consultancy; Novartis: Consultancy; Genmab: Consultancy. Freeman: Amgen: Honoraria; Celgene: Honoraria; Sanofi: Honoraria, Speakers Bureau; Incyte: Honoraria; Abbvie: Honoraria; Teva: Research Funding; Roche: Research Funding; Bristol Myers Squibb: Honoraria, Speakers Bureau; Janssen: Honoraria, Speakers Bureau; Seattle Genetics: Honoraria.

scholarly journals Frontline Therapy with Bendamustine and Rituximab (BR) in Follicular Lymphoma: Prognosis Among Patients with Progression of Disease By 24 Months (POD24) Is Poor with Majority Having Transformed Lymphoma

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2873-2873 ◽  
Author(s):  
Ciara Louise Freeman ◽  
Kerry J Savage ◽  
Diego Villa ◽  
David W. Scott ◽  
Alina S. Gerrie ◽  
...  
Keyword(s):  
Systemic Therapy ◽  
Research Funding ◽  
Population Based ◽  
Advanced Stage ◽  
Historical Cohort ◽  
Treatment Toxicity ◽  
Early Progression ◽  
Transformed Lymphoma ◽  
Frontline Therapy

Abstract Background: Bendamustine and rituximab (BR) has been a preferred regimen for frontline therapy of patients (pts) with advanced stage follicular lymphoma (FL) since randomized trials demonstrated both favorable efficacy and toxicity profiles (Rummel et al 2013, Flinn et al 2014). However, the incidence of transformation and outcomes of pts with early progression within 24 months (POD24) after BR remain poorly documented. Since 2013, BR has been the recommended frontline therapy for all pts with advanced stage, symptomatic FL in British Columbia (BC). We report this population-based analysis evaluating outcomes following the introduction of BR, including the incidence of transformation and POD24, compared to a historical cohort of pts treated with frontline RCVP. Methods: The BC Lymphoid Cancer Database was used to identify all FL pts treated with frontline BR prior to April 1st 2018. A period of observation prior to systemic therapy was permitted, but pts were excluded if they received prior radiation or single-agent rituximab. All pts had pathologically confirmed FL grades 1-3A and symptomatic advanced stage disease (Ann-Arbor I/II if too bulky/not amenable to radiation or stage III-IV). Pts were excluded if they were HIV positive or had documented discordant/composite lymphoma. Event-free survival (EFS), overall survival (OS), and time-to-transformation (TTTF) were calculated from the date of initiation of systemic therapy. Early progression (POD24) was defined as relapse or progression, death from lymphoma or treatment toxicity within 24 months of initiation of systemic therapy. Outcomes were compared with a historical cohort of pts treated with frontline RCVP, which was the recommended induction prior to BR. All pts were eligible to receive rituximab maintenance, which is standard of care for responding pts post-induction therapy in BC. Results: A total of 296 BR-treated pts were identified with a median age of 61 years (range 24-86) and baseline characteristics as outlined in Table 1. Only 34 (11%) had been previously observed and 239 (81%) received rituximab maintenance. A historical cohort of 347 RCVP-treated pts was identified, with comparable clinical characteristics but longer duration of follow-up (median 8.4y, range 0.6-12.6). With a median follow-up for living pts of 2.8y (range 0.2-7.6), estimates for 2-y EFS and OS were 85% (95% CI 80-89%) and 92% (95% CI 88-95%), respectively, for BR-treated pts. As expected, use of BR was associated with an improvement in EFS compared with RCVP (2-y EFS 76% [95% CI 71-80%], p=0.001), but no difference in OS with current follow-up. A total of 28 (9%) transformations have occurred in BR-treated pts, 68% of which were documented histologically. Only elevated LDH was associated with increased risk of transformation (p<0.001). Compared with RCVP-treated pts, the incidence of transformation over time appears similar with current follow-up (Figure 1). Post-transformation outcome in BR-treated pts was poor, with 2-y OS 39% (95% CI 18-59). Early progression (POD24) has occurred in 35/296 (12%) of BR-treated pts. The majority of these, 27 (77%), had transformed lymphoma. Five POD24 pts (14%) died of lymphoma or treatment toxicity without documented transformation and 3 (9%) had relapse with FL and are still alive at last follow up. By comparison, POD24 occurred in 77/347 (22%) of RCVP-treated pts: comprising 31 (40%) transformed lymphoma, 27 (35%) died of lymphoma or treatment toxicity without documented transformation and 19 (25%) relapsed with FL and are still alive at last follow up. Outcome in BR-treated pts with POD24 was poor, with post-progression 2y OS 38% (95% CI 20-55%) compared to non-POD24 BR-treated patients (Figure 2). Conclusion: This population-based analysis demonstrates that in the absence of transformation or POD24, pts with advanced stage FL have excellent outcomes after frontline BR. The use of BR has not changed the rate of transformation compared with that seen after frontline RCVP, with limited follow-up. The occurrence of early progression (POD24) may be decreasing following the introduction of BR, but the majority of POD24 pts now have transformed lymphoma. As a consequence, only a small proportion of POD24 pts following BR have FL-only relapse that may be considered for novel approaches specific for FL. A greater impact on outcome for POD24 pts after BR will require early prediction and improved treatment of transformed lymphoma. Disclosures Freeman: Seattle Genetics: Honoraria; Abbvie: Honoraria. Scott:NanoString: Patents & Royalties: Named Inventor on a patent licensed to NanoString Technologies, Research Funding; Janssen: Research Funding; Celgene: Consultancy, Honoraria; Roche: Research Funding. Connors:Merck: Research Funding; Janssen: Research Funding; Bristol Myers-Squibb: Research Funding; Cephalon: Research Funding; NanoString Technologies: Patents & Royalties: Named Inventor on a patent licensed to NanoString Technologies, Research Funding; Bayer Healthcare: Research Funding; Genentech: Research Funding; Lilly: Research Funding; Seattle Genetics: Honoraria, Research Funding; F Hoffmann-La Roche: Research Funding; Roche Canada: Research Funding; Takeda: Research Funding; Amgen: Research Funding. Sehn:Karyopharm: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Roche/Genentech: Consultancy, Honoraria; Morphosys: Consultancy, Honoraria; TG Therapeutics: Consultancy, Honoraria; Merck: Consultancy, Honoraria; Lundbeck: Consultancy, Honoraria; Janssen: Consultancy, Honoraria.

scholarly journals Impact of Disease Extent and Distribution on Outcomes in Stage II Follicular Lymphoma Treated with Curative-Intent Radiation Therapy

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2431-2431
Author(s):  
Yi Xu ◽  
Matthew Chan ◽  
Tom Pickles ◽  
Jessica Chan ◽  
Laurie H. Sehn ◽  
...  
Keyword(s):  
Gene Expression ◽  
Clinical Trial ◽  
Lymph Node ◽  
Gene Expression Profiling ◽  
Expression Profiling ◽  
Research Funding ◽  
Stage Ii ◽  
Study Cohort ◽  
Disease Extent ◽  
Curative Intent

Abstract Background: Follicular lymphoma (FL) is the most common indolent non-Hodgkin's lymphoma, with 8% of patients presenting with stage II disease. Stage II FL is potentially curable with radiation therapy (RT), but more than half of patients relapse within 10 years. The Ann Arbor stage II definition encompasses a broad spectrum of disease extents and distributions; understanding how these factors affect outcomes could enable identification of patients at higher risk for progression. The purpose of this study was to investigate the impact of disease extent and distribution on outcomes in stage II FL. Methods: The study included patients who were diagnosed with stage II or IIE, grade 1-3A FL from 1980 to 2016 at BC Cancer, had non-mesenteric disease, and were treated with curative-intent (≥ 20 Gy) RT alone. Our provincial recommendation was to use curative-intent RT for limited-stage patients, with limited stage defined as stage I or II, non-bulky, radio-encompassable disease with no B symptoms. Prior to February 1998, the provincial policy was to use involved regional RT. In March 1998, the policy was changed to use involved-site RT. Medical records were retrospectively reviewed for patient, disease, and treatment characteristics and outcomes. Survival estimates were calculated using the Kaplan-Meier method starting from the diagnosis date. Events were defined as relapse for freedom from progression (FFP), relapse or death from any cause for progression-free survival (PFS), death due to FL or FL treatment for disease-specific survival (DSS), and death from any cause for overall survival (OS). Univariable analyses (UVA) were performed using the log-rank test, and multivariable analyses (MVA) were performed using the Cox proportional hazards model. Results were considered significant if p ≤ 0.05. Results: 222 patients were diagnosed with stage II, grade 1-3A FL from 1980 to 2016. 56 patients were excluded due to mesenteric involvement. Of the 166 remaining non-mesenteric patients, 16 were excluded due to treatment with chemoimmunotherapy only, 28 due to combined modality therapy, 3 due to palliative RT, 19 due to management with watchful waiting, and 1 due to treatment refusal. The remaining 99 patients formed our study cohort. The median follow-up duration of living patients was 13.6 years (range, 4.8-35.4). The median age at diagnosis was 59.5 years (range, 33.2-86.2), and 56% of patients were male. Eastern Cooperative Oncology Group (ECOG) performance status was 0 in 68% of patients and 1-2 in 34%. 18% of patients had extranodal disease, 11% had grade 3A disease, 4% had complete resection of disease prior to RT, and 2% had elevated lactate dehydrogenase (LDH). The median greatest diameter of any individual mass was 3.6 cm. 11% had 1 involved lymph node region (staged as IIE due to extranodal disease), 64% had 2 regions, 18% had 3 regions, and 7% had 4 regions. Table 1 shows the FFP, PFS, DSS, and OS at 5, 10, and 15 years for the study cohort. Of the 57 patients who relapsed, 1 (2%) had in-field relapse only, 1 (2%) had in-field and marginal relapse, 9 (16%) had in-field and distant (± marginal) relapse, 2 (4%) had marginal relapse only, 7 (12%) had marginal and distant relapse, 36 (63%) had distant relapse only, and 1 (2%) had unknown site(s) of relapse. On UVA (Table 2), age ≥ 60 years was associated with inferior DSS and OS; greatest diameter ≥ 3.5 cm was associated with inferior FFP and PFS (Figure 1A and 1B); disease involving the paraaortic region was associated with inferior FFP and PFS; and involvement of 4 lymph node regions was associated with inferior PFS (Figure 1D). On MVA (Table 3), greatest diameter ≥ 3.5 cm and involvement of 4 lymph node regions were associated with an inferior FFP and PFS, while older age was associated with an inferior DSS and OS. Bilateral disease, infradiaphragmatic disease, and extranodal involvement did not correlate with worse outcomes on UVA or MVA. Conclusions: Greatest diameter of disease ≥ 3.5 cm and involvement of 4 lymph node regions are significantly associated with inferior FFP and PFS in stage II FL patients with non-mesenteric disease and treated with curative-intent RT alone. Bilateral disease, infradiaphragmatic disease, and extranodal involvement are not associated with worse outcomes. These results may assist clinicians with identifying specific patients in this population at higher risk for progression, facilitating improved treatment decision-making and patient counselling. Figure 1 Figure 1. Disclosures Sehn: Genmab: Consultancy; Novartis: Consultancy; Debiopharm: Consultancy. Scott: Janssen: Consultancy, Research Funding; Rich/Genentech: Research Funding; NanoString Technologies: Patents & Royalties: Patent describing measuring the proliferation signature in MCL using gene expression profiling.; BC Cancer: Patents & Royalties: Patent describing assigning DLBCL COO by gene expression profiling--licensed to NanoString Technologies. Patent describing measuring the proliferation signature in MCL using gene expression profiling. ; Abbvie: Consultancy; Incyte: Consultancy; Celgene: Consultancy; AstraZeneca: Consultancy. Villa: Janssen: Honoraria; Roche: Honoraria; Gilead: Honoraria; AstraZeneca: Honoraria; AbbVie: Honoraria; Seattle Genetics: Honoraria; Celgene: Honoraria; Lundbeck: Honoraria; NanoString Technologies: Honoraria. Gerrie: Janssen: Honoraria, Research Funding; Sandoz: Honoraria; AbbVie: Honoraria, Research Funding; Astrazeneca: Honoraria, Research Funding; Roche: Research Funding. Savage: Roche: Research Funding; Servier: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria; Astra-Zeneca: Consultancy, Honoraria; Merck: Consultancy, Honoraria, Other: Institutional clinical trial funding; BMS: Consultancy, Honoraria, Other: Institutional clinical trial funding; Takeda: Other: Institutional clinical trial funding; Beigene: Other: Institutional clinical trial funding; Genentech: Research Funding.

scholarly journals The Genomic Landscape of Plasmablastic Lymphoma (PBL) - an L.L.M.P.P. Project

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1326-1326
Author(s):  
Jasper Wong ◽  
Brett Collinge ◽  
Laura K Hilton ◽  
Susana Ben-Neriah ◽  
Graham W. Slack ◽  
...  
Keyword(s):  
Gene Expression ◽  
Clinical Trial ◽  
B Cell ◽  
Gene Expression Profiling ◽  
Board Of Directors ◽  
Cell Fate ◽  
Expression Profiling ◽  
Research Funding ◽  
Advisory Committees ◽  
Genomic Landscape

Abstract Introduction: Plasmablastic lymphoma (PBL) is an aggressive B-cell lymphoma that predominantly occurs in patients with HIV or other causes of immunodeficiency. Frequent infection by the Epstein-Barr virus (EBV) and MYC translocations have been described as major features contributing to the pathogenesis of PBL. Prior studies examining the genetic landscape of PBL have largely relied on targeted capture-based sequencing approaches. As such, the molecular features of PBL remain to be fully explored. Here, we provide a comprehensive description of the genomic landscape of PBL using whole-genome and whole-exome sequencing to identify commonly perturbed pathways. Method: Archival diagnostic fresh frozen and formalin fixed paraffin embedded tissue biopsies from 58 PBL tumours were accrued from Lymphoma/Leukemia Molecular Profiling Project (LLMPP) sites, including 15 tumours from Ramis-Zaldivar et al., Haematolgica 2021. MYC rearrangements were identified by break-apart fluorescent in situ hybridization (FISH) and rearrangement partner was determined in a subset of tumours from capture or genome sequencing data using structural variant callers Manta, GRIDSS, and Delly. High confidence somatic mutations (SNVs/Indels) were identified in data from whole-genome (n=5) or whole-exome (n=53) sequencing through an ensemble voting approach utilizing four variant callers (Strelka2, Lofreq, Mutect2, SAGE). Mutation frequencies in known lymphoma-related genes were compared to activated B-cell (ABC)-DLBCL (Schmitz et al., NEJM 2018), as the closest tumour entity in terms of putative cell-of-origin differentiation stage, to identify differences in genetic aberrations. Candidate somatic copy number alterations (CNAs) were identified from exome and genome sequencing data, using CopywriteR and ControlFREEC, respectively, and high-confidence CNAs were determined using GISTIC2.0. Results: Within the study cohort, 81% of patients were male with a median age of 59 years (range 11-88). HIV and EBV statuses were available for 47% of patients and 95% of tumours, respectively, with 49% (13/27) of the patients being HIV+ and 69% (38/55) of tumours being EBV+. MYC rearrangement was observed in 60% (35/58) of PBLs, with IGH as the partner gene in 88% (21/24) of tumours. The most frequently mutated genes were STAT3 (38%), TP53 (22%), NRAS (21%), and TET2 (16%), consistent with previous studies, however novel mutations were seen in DUSP2 (21%), KLHL6 (16%), and BHLHE41 (16%). Recurrent CNAs included amplifications in 1q, whole gains of 7, 8q24, 11p12 and deletions affecting 4p16, 5p15, 10q11.22. While the mutational landscapes were similar between samples with and without a MYC translocation, the MYC-translocated PBLs showed more frequent amplification of 1q32.1. When stratifying by EBV status, STAT3 and SOCS1 mutations were more frequent in EBV-positive tumours, whereas TP53, TET2, KRAS, and MMRN2 mutations were associated with EBV-negativity. In comparison to ABC-DLBCL, PBLs were significantly enriched in STAT3 and NRAS mutations, and lacked common mutations affecting the NF-κB pathway (eg. MYD88, CD79B, and NFKBIZ 3' UTR mutations). Mutations in genes that are frequently mutated in ABC-DLBCLs, such as those associated with plasma cell differentiation (eg. PRDM1) or a memory B-cell fate (eg. TBL1XR1), were also not mutated in PBLs. Finally, genetic alterations associated with immune evasion, such as deletion of MHC I and II and mutations in B2M, CIITA, and CD58, were rarely observed. Conclusion: These data present a comprehensive overview of the genomic landscape of PBLs in a large cohort. We show frequent mutations involving the JAK-STAT and MAPK pathways, wherein the genetic landscape can be differentially characterized by EBV status and MYC rearrangement status. We show that PBLs are genetically distinct from ABC-DLBCLs, with absence of mutations in genes affecting the NF-κB pathway, immune evasion, and driving a memory B-cell fate. Disclosures Slack: Seagen: Consultancy, Honoraria. Raess: Scopio Labs: Research Funding. Holte: Gilead: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; Nordic: Membership on an entity's Board of Directors or advisory committees; Nanovector: Membership on an entity's Board of Directors or advisory committees, Other: lectures honorarias; Novartis: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees. Savage: Servier: Consultancy, Honoraria; Roche: Research Funding; BMS: Consultancy, Honoraria, Other: Institutional clinical trial funding; Astra-Zeneca: Consultancy, Honoraria; Merck: Consultancy, Honoraria, Other: Institutional clinical trial funding; AbbVie: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria; Takeda: Other: Institutional clinical trial funding; Beigene: Other: Institutional clinical trial funding; Genentech: Research Funding. Steidl: Seattle Genetics: Consultancy; Curis Inc.: Consultancy; Bayer: Consultancy; Epizyme: Research Funding; Trillium Therapeutics: Research Funding; AbbVie: Consultancy; Bristol-Myers Squibb: Research Funding. Rimsza: NanoString Technologies: Other: Fee-for-service contract. Morin: Foundation for Burkitt Lymphoma Research: Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy; Epizyme: Patents & Royalties. Scott: Abbvie: Consultancy; AstraZeneca: Consultancy; Rich/Genentech: Research Funding; BC Cancer: Patents & Royalties: Patent describing assigning DLBCL COO by gene expression profiling--licensed to NanoString Technologies. Patent describing measuring the proliferation signature in MCL using gene expression profiling. ; Incyte: Consultancy; Janssen: Consultancy, Research Funding; Celgene: Consultancy; NanoString Technologies: Patents & Royalties: Patent describing measuring the proliferation signature in MCL using gene expression profiling..

scholarly journals Single-Cell Profiling Reveals Clinically Relevant Evolutionary Trajectories and Alternate Biologies in Human Follicular Lymphoma

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 450-450
Author(s):  
Xuehai Wang ◽  
Michael Nissen ◽  
Deanne Gracias ◽  
Manabu Kusakabe ◽  
Guillermo Simkin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Clinical Trial ◽  
T Cell ◽  
B Cells ◽  
Gene Expression Profiling ◽  
Expression Profiling ◽  
Research Funding ◽  
Phenotypic Diversity ◽  
Type B ◽  
High Entropy

Abstract Follicular lymphoma (FL) is an indolent lymphoma of mature B-cells but may transform to a more aggressive histology, most commonly diffuse large B cell lymphoma. Recurrent mutations associated with transformation have been identified; however, biological predictors to guide initial therapy have remained elusive. We hypothesized that clonal heterogeneity and patient-specific immune responses would contribute to variable clinical outcomes and that understanding the complexity of the entire tumor "ecosystem" would allow more individualized matching of patients with specific therapies. In prior ASH meetings, we presented preliminary analyses of B and T cell-focused phenotypic profiling of 155 newly diagnosed pre-treatment FL biopsy samples at single cell resolution by mass cytometry (CyTOF). These prior analyses unexpectedly revealed two distinct evolutionary trajectories which were independently reflected in both B and T cell compartments. One trajectory expectedly involved germinal center B cells (GCB); however, the other was more related to naïve/memory B-cells (NMB). Interestingly, cluster co-occurrence analysis suggested that the GCB and NMB trajectories were mutually exclusive of another and tended not to be found within the same tumor despite their high prevalences (χ 2 = 29.8, DF=1, p=4.8e-8; χ 2 test). Clustering analysis based on relative abundances of T cell subsets revealed 4 distinct immune patterns: Group 1 was characterized by naive T cells; Group 2 by T follicular helper (Tfh) cells; Group 3 by CD4+ regulatory T (Treg) and CD8 effector memory cells (CD8EM); and Group 4 by a diverse complement of naive, memory, and differentiated effector subsets. We report here further analyses, now incorporating DNA mutational and clinical outcome information. Tumors were parsed into 3 types based on the phenotype of the majority (&gt;50%) of tumor cells present in the diagnostic biopsy: Type A tumors dominated by GCB cells (28% of samples), type B tumors dominated by NMB cells (18% of samples), and type nonA/nonB tumors dominated by neither GCB nor NMB cells (54% of samples). Type A tumors were significantly enriched for mutations in EZH2, TNFRSF14, and MEF2B, while no significant mutational associations were seen in type B and nonA/nonB tumors. Type B was significantly associated with increased risk of transformation, and when combined with a measure of intratumoral phenotypic diversity ("Entropy"), we found that type B tumors with high (above median) Entropy, representing 8.5% of all cases, exhibited a hazard ratio (HR) of 5.9 for transformation risk in comparison to all others combined (log-rank p&lt;0.0001). Type B and high Entropy remained significant in multivariate analysis (p=0.043 and p=0.011, respectively), whereas high risk FLIPI score did not (p=0.962). We also investigated survival outcomes using a sub-cohort of 108 patients who had received bendamustine + rituximab (BR) as their primary therapy. Despite the association of type B tumors with transformation risk, patients with type nonA/nonB tumors exhibited the poorest outcomes as measured by disease-specific survival (DSS; 5yr survival 78% vs 98% for all others combined, log-rank p=0.0241). Combining type nonA/nonB with high Entropy defined 20% of patients with significantly shorter DSS (HR 5.3, log-rank p=0.0019). In multivariate analysis, type nonA/nonB and high risk FLIPI score were significant (p=0.038 and 0.035, respectively), while high Entropy trended with inferior DSS (HR 2.8, 95% CI 0.76-10; p=0.123). Taken together, these data support that CyTOF-defined phenotypic subtypes of FL and intratumoral phenotypic diversity identify clinically significant subgroups at initial diagnosis and compare favorably against FLIPI score in predicting both risk of transformation and inferior DSS. Figure 1 Figure 1. Disclosures Freeman: Incyte: Honoraria; Seattle Genetics: Honoraria; Sanofi: Honoraria, Speakers Bureau; Bristol Myers Squibb: Honoraria, Speakers Bureau; Amgen: Honoraria; Janssen: Honoraria, Speakers Bureau; Celgene: Honoraria; Teva: Research Funding; Abbvie: Honoraria; Roche: Research Funding. Sehn: Genmab: Consultancy; Novartis: Consultancy; Debiopharm: Consultancy. Savage: BMS: Consultancy, Honoraria, Other: Institutional clinical trial funding; Seattle Genetics: Consultancy, Honoraria; Astra-Zeneca: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria; Merck: Consultancy, Honoraria, Other: Institutional clinical trial funding; Takeda: Other: Institutional clinical trial funding; Roche: Research Funding; Servier: Consultancy, Honoraria; Beigene: Other: Institutional clinical trial funding; Genentech: Research Funding. Craig: Bayer: Consultancy. Scott: Abbvie: Consultancy; AstraZeneca: Consultancy; Incyte: Consultancy; Celgene: Consultancy; NanoString Technologies: Patents & Royalties: Patent describing measuring the proliferation signature in MCL using gene expression profiling.; BC Cancer: Patents & Royalties: Patent describing assigning DLBCL COO by gene expression profiling--licensed to NanoString Technologies. Patent describing measuring the proliferation signature in MCL using gene expression profiling. ; Rich/Genentech: Research Funding; Janssen: Consultancy, Research Funding. Steidl: Trillium Therapeutics: Research Funding; Bristol-Myers Squibb: Research Funding; AbbVie: Consultancy; Seattle Genetics: Consultancy; Curis Inc.: Consultancy; Bayer: Consultancy; Epizyme: Research Funding.

scholarly journals Population-Wide Introduction of Dose-Adjusted EPOCH-R Is Associated with Improved Outcome of High Grade B-Cell Lymphoma with MYC and BCL2 Rearrangements with Diffuse Large B-Cell Lymphoma Morphology

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1458-1458
Author(s):  
Waleed Alduaij ◽  
Laurie H. Sehn ◽  
Aixiang Jiang ◽  
Susana Ben-Neriah ◽  
Brett Collinge ◽  
...  
Keyword(s):  
Gene Expression ◽  
Clinical Trial ◽  
B Cell ◽  
Gene Expression Profiling ◽  
Expression Profiling ◽  
Research Funding ◽  
De Novo ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
High Grade

Abstract Introduction: High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements (HGBL-DH/TH), colloquially referred to as double- or triple-hit lymphoma, is associated with poor outcomes prompting many centers to use dose-intensive immunochemotherapy. The benefit of treatment intensification in patients with HGBL-DH/TH with diffuse large B-cell lymphoma (DLBCL) morphology, who would otherwise receive standard-of-care rituximab, cyclophosphamide, vincristine and prednisone (R-CHOP), remains unclear because suitably powered randomized clinical trials have not been performed, and earlier studies included patients with high-grade morphology. Furthermore, selection bias due to the restriction of fluorescence in situ hybridization (FISH) testing to diagnose HGBL-DH/TH in patients with high-risk clinical presentation or aggressive tumor morphology confounds historical comparators. Since 2015, de novo DLBCL biopsies in British Columbia (BC) have undergone routine FISH testing in clinical practice. Concurrently, provincial guidelines were introduced recommending treatment with dose-adjusted etoposide, doxorubicin, vincristine, cyclophosphamide, prednisone and rituximab (DA-EPOCH-R) for appropriately fit patients aged 75 years (y) or younger with HGBL-DH/TH harboring BCL2 rearrangements with DLBCL morphology (HGBL-DH/TH-BCL2-DLBCL). A population-based analysis was conducted to assess the impact of the introduction of DA-EPOCH-R on outcomes in HGBL-DH/TH-BCL2-DLBCL. Methods: Outcomes of HGBL-DH/TH-BCL2-DLBCL patients diagnosed between 2015 to 2020 using clinical FISH performed on de novo DLBCL biopsies (DA-EPOCH-R era) were compared to patients with HGBL-DH/TH-BCL2-DLBCL identified from a historic province-wide cohort of de novo DLBCL diagnosed between 2005-2010 in BC that underwent universal FISH in a research setting (R-CHOP era). Patients with the rarer entity of HGBL-DH/TH harboring MYC and BCL6 rearrangements only (HGBL-DH-BCL6) were excluded and were not part of the original DA-EPOCH-R guideline. Multivariable Cox proportional hazards regression models were used to predict the independent effect of treatment era after controlling for the International Prognostic Index (IPI). Results: 99 patients with HGBL-DH/TH-BCL2-DLBCL were identified through routine clinical FISH in the DA-EPOCH-R era. Of 1172 de novo DLBCL patients in the historic R-CHOP era, 824 had adequate diagnostic material for evaluation by FISH, 52 of which were HGBL-DH/TH-BCL2-DLBCL. The analysis was restricted to patients aged 75y or younger, yielding 71 and 38 patients in the DA-EPOCH-R and R-CHOP eras, respectively. 7/38 (18%) biopsies in the R-CHOP era had undergone clinical FISH testing at diagnosis with results known to the treating physician. Median (interquartile range) follow-up in living patients was 2.8y (2.0-4.4y) in the DA-EPOCH-R era and 12.2y (11.2-13.4y) in the R-CHOP era. 49/71 (69%) patients received DA-EPOCH-R in the DA-EPOCH-R era, whereas 32/38 patients (84%) received R-CHOP in the R-CHOP era. Both eras had comparable baseline clinical characteristics with no significant difference in IPI risk groups (Table 1). The DA-EPOCH-R era was associated with superior 2-year time to progression (TTP, 73.9% vs 47.4%, p=0.016) and overall survival (OS, 77.7% vs 50.0%, p=0.022, Figure 1). After adjusting for IPI risk groups (low 0-2, high 3-5), the DA-EPOCH-R era was independently associated with superior TTP (hazard ratio (HR) 0.41, 95% confidence interval (CI) 0.21-0.77, p=0.005) and OS (HR 0.39, 95% CI 0.21-0.76, p=0.005). After controlling for individual IPI factors, treatment era remained predictive of TTP (HR 0.38, 95% CI 0.19- 0.76, p=0.006) and OS (HR 0.39, 95% CI 0.19-0.79, p=0.008). Conclusions: Introduction of a provincial, population-based recommendation to use DA-EPOCH-R for appropriately fit patients aged 75y or younger is associated with improved real-world outcomes of HGBL-DH/TH-BCL2-DLBCL. The similarity between TTP and OS within each era suggests the high failure rate of conventional salvage therapy irrespective of frontline treatment, prompting further investigation of novel second-line therapies in this poor-prognosis population. Targeted capture sequencing to identify MYC translocation partners is underway, and the influence of the MYC partner on outcomes in both eras will be presented. Figure 1 Figure 1. Disclosures Sehn: Novartis: Consultancy; Genmab: Consultancy; Debiopharm: Consultancy. Slack: Seagen: Consultancy, Honoraria. Craig: Bayer: Consultancy. Villa: Janssen: Honoraria; Gilead: Honoraria; AstraZeneca: Honoraria; AbbVie: Honoraria; Seattle Genetics: Honoraria; Celgene: Honoraria; Lundbeck: Honoraria; Roche: Honoraria; NanoString Technologies: Honoraria. Gerrie: Sandoz: Honoraria; Roche: Research Funding; Astrazeneca: Honoraria, Research Funding; AbbVie: Honoraria, Research Funding; Janssen: Honoraria, Research Funding. Freeman: Teva: Research Funding; Roche: Research Funding; Janssen: Honoraria, Speakers Bureau; Amgen: Honoraria; Celgene: Honoraria; Sanofi: Honoraria, Speakers Bureau; Incyte: Honoraria; Abbvie: Honoraria; Seattle Genetics: Honoraria; Bristol Myers Squibb: Honoraria, Speakers Bureau. Savage: Seattle Genetics: Consultancy, Honoraria; Roche: Research Funding; Astra-Zeneca: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria; Merck: Consultancy, Honoraria, Other: Institutional clinical trial funding; BMS: Consultancy, Honoraria, Other: Institutional clinical trial funding; Servier: Consultancy, Honoraria; Takeda: Other: Institutional clinical trial funding; Beigene: Other: Institutional clinical trial funding; Genentech: Research Funding. Steidl: Bayer: Consultancy; Trillium Therapeutics: Research Funding; Curis Inc.: Consultancy; AbbVie: Consultancy; Epizyme: Research Funding; Seattle Genetics: Consultancy; Bristol-Myers Squibb: Research Funding. Scott: Celgene: Consultancy; NanoString Technologies: Patents & Royalties: Patent describing measuring the proliferation signature in MCL using gene expression profiling.; BC Cancer: Patents & Royalties: Patent describing assigning DLBCL COO by gene expression profiling--licensed to NanoString Technologies. Patent describing measuring the proliferation signature in MCL using gene expression profiling. ; Rich/Genentech: Research Funding; Janssen: Consultancy, Research Funding; Incyte: Consultancy; Abbvie: Consultancy; AstraZeneca: Consultancy.

scholarly journals Three Years Follow-Up Study Showed Prenatal Methamphetamine Exposure May Cause Chronic Abnormalities In Transcriptomic Pattern

2021 ◽  
Author(s):  
Arvin Haghighatfard ◽  
Soha Seifollahi ◽  
Pegah Rajabi ◽  
Niloofar Rahmani ◽  
Rojin Ghannadzadeh
Keyword(s):  
Gene Expression ◽  
Gene Expression Profiling ◽  
Expression Profiling ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Rna Extraction ◽  
Childbearing Age ◽  
Methamphetamine Use ◽  
Methamphetamine Use Disorder

Abstract Background: The high rate of methamphetamine use disorder among young adults and women of childbearing age makes it imperative to clarify the long-term effects of Methamphetamine exposure on the offspring. Behavioral and cognitive problems had been reported in children with parental Methamphetamine exposure (PME). The present study aimed to assess the acute and chronic effects of PME in molecular regulations and gene expression profiles of children during their first years of life.Methods: All subjects were recruited before birth, and sampling was conducted from the first ten days of birth, twelve months, twenty months, and thirty-six months of age. Finally, 2658 children with PME and 3573 normal children had been finished the follow-up. RNA extraction was operated from blood samples and gene expression profiling was conducted by using the Affymetrix GeneChip Human Genome U133 plus 2.0 Array Platform. Gene expression data were confirmed by Real-time PCR. Results: Gene expression profiling during thirty-six months showed several constant mRNA level alterations in children with PME compared with normal. These genes are involved in several gene ontologies and pathways involved with the immune system, neuronal functions, and bioenergetic metabolism. It seems that Methamphetamine use disorder before and during the pregnancy period may affect the expression profile of children, and these changes could remain years after birth. Affected genes have some similarities with the gene expression patterns of addiction, psychiatric disorders, neurodevelopmental disabilities, and immune deficiencies. Conclusion: Findings may shed light on the molecular effects of prenatal methamphetamine exposure and may lead to new psychological and somatic caring protocols for these children based on their potential abnormalities.

scholarly journals Population-based study of the effect of gene expression profiling on adjuvant chemotherapy use in breast cancer patients under the age of 65 years

Cancer ◽  
2015 ◽  
Vol 121 (22) ◽  
pp. 4062-4070 ◽  
Author(s):  
Arnold L. Potosky ◽  
Suzanne C. O'Neill ◽  
Claudine Isaacs ◽  
Huei-Ting Tsai ◽  
Calvin Chao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Adjuvant Chemotherapy ◽  
Gene Expression Profiling ◽  
Cancer Patients ◽  
Expression Profiling ◽  
Population Based ◽  
Breast Cancer Patients ◽  
Population Based Study

Gene Expression Profiling within the Context of JAK Inhibitor Therapy for Myelofibrosis: Correlation with Treatment Effect and Anemia Response

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1751-1751
Author(s):  
Animesh Pardanani ◽  
Rebecca R. Laborde ◽  
Terra L Lasho ◽  
Christy Finke ◽  
Alexey A. Leontovich ◽  
...  
Keyword(s):  
Gene Expression ◽  
Clinical Trial ◽  
Immune Response ◽  
Gene Expression Profiling ◽  
Pathway Analysis ◽  
Treatment Effect ◽  
Expression Profiling ◽  
Phase 1 ◽  
Hemoglobin Level ◽  
Jak Inhibitors

Abstract Abstract 1751 Background: JAK inhibitors have significant palliative benefit in myelofibrosis (MF), mainly in the form of improved constitutional symptoms and reduced splenomegaly. Preliminary data suggests that CYT387, a JAK-1/2 inhibitor, also has the ability to produce anemia responses (ASH Annual Meeting, 2011). In general, the mechanism(s) underlying treatment effects of JAK inhibitors remain unclear but likely represent a drug-specific balance between anti-clonal activity and modulation of immuno cellular-cytokine pathways. We conducted a gene expression profiling (GEP) study using primary cells from MF patients undergoing therapy with CYT387 followed by correlation with clinical data. Methods: Study subjects were enrolled in the Phase-1/2 study of CYT387 treatment in patients with primary (PMF), post-polycythemia vera (PPMF) or post-essential thrombocythemia (PTMF) myelofibrosis. Paired research samples were collected; the time points were pre-study and 12 weeks after commencing study treatment. PBMCs were purified from whole blood by Ficoll separation; RNA was isolated from this cell fraction for GEP analysis. Gene expression profiles were generated using Illumnia Human HT-12 v4 microarray. Pair wise analysis was conducted using the Wilcoxon signed-rank test with a p-value cutoff of 0.05 to generate lists of differentially expressed genes between assigned groups. Pathway analysis was conducted to identify relevant pathways enriched for differentially expressed genes. Comprehensive plasma cytokine profiling was performed using Multiplex Bead-Based Luminex technology (Invitrogen, Carlsbad, CA). Results: Seventeen patients were studied based on sample availability; 11 (65%) mere male with median age of 66 years (range 53–85). Twelve (71%) were JAK2V617F mutation positive and the DIPSS-plus risk categorization was 10 (59%) high and 7 (41%) intermediate-2. All patients were evaluable for anemia response; 14 (82%) were red cell transfusion dependent at study start. Nine (53%) patients achieved anemia response by IWG-MRT criteria; of these, 8 patients achieved transfusion independence (minimum non-transfused hemoglobin level of 8 g/dL maintained for at least 12 weeks) and 1 had a sustained >2 g/dL increase in hemoglobin level above baseline. The initial pair wise analysis to identify differential patterns of gene expression compared pre- and post-treatment groups (Figure 1A). This revealed a cluster of significantly (p <0.05) down-regulated genes (minimum 2-fold; median 17-fold) following treatment (displayed in green; upper left quadrant). Pathway enrichment analysis revealed significant associations of these genes with cytokine regulation of immune response, cell proliferation, chemotaxis and cytoskeleton remodeling. We then conducted a pair wise analysis of anemia responders versus non-responders; this revealed a predominance of over expressed gene targets (median 35-fold) in the anemia responder group (Figure 1B) (displayed in red; upper right quadrant). Similar pathway analysis identified enrichment for genes involved in immune system function in this cluster. Conclusions: The current preliminary analysis suggests that genes relevant to immune response-cytokine pathways are significantly over expressed in patients who achieve anemia response following CYT387 therapy. This further suggests a dominant immune component that underpins ineffective hematopoiesis in responding patients. On the basis of broad treatment-related changes in gene expression we suggest that an important component of CYT387's treatment effect is down regulation of these dysregulated pathways. Ongoing studies include validation of select gene targets which will be tested prospectively in future treatment protocols, as well as correlation of gene expression with circulating cytokine-chemokine levels. Disclosures: Pardanani: Bristol-Myers Squibb: Clinical trial support, Clinical trial support Other; YM BioSciences: Clinical trial support, Clinical trial support Other; Sanofi-Aventis: Clinical trial support Other. Off Label Use: Data from Phase −1/2 study of CYT387 use in myelofibrosis is mentioned.

MyPRSR Molecular Subtypes of Multiple Myeloma Represent All High-Risk FISH Translocations Included in the mSMART 2.0 and R-ISS Guidelines

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3264-3264 ◽  
Author(s):  
Ryan K Van Laar ◽  
Ivan Borrelo ◽  
David Jabalayan ◽  
Ruben Niesvizky ◽  
Aga Zielinski ◽  
...  
Keyword(s):  
Gene Expression ◽  
Multiple Myeloma ◽  
High Risk ◽  
Gene Expression Profiling ◽  
Expression Profiling ◽  
Research Funding ◽  
Plasma Cells ◽  
Molecular Subtypes ◽  
Risk Status ◽  
Significant Difference

Abstract Background: There is a global consensus that multiple myeloma patients with high-risk disease require additional monitoring and therapy compared to low/standard risk patients in order to maximize their chances of survival. Current diagnostic guidelines recommend FISH-based assessment of chromosomal aberrations to determine risk status (i.e. t(14;20), t(14;16), t(4;14) and/or Del17p), however, studies show FISH for MM may have a 20-30% QNS rate and is up to 15% discordant between laboratories, even when starting from isolated plasma cells. In this study we demonstrate that MyPRS gene expression profiling reproduces the key high risk translocations for MM risk stratification, in addition to having other significant advantages. Methods: Reproducibility studies show that MyPRS results are less than 1% discordant starting from isolated plasma cells and return successful results in up to 95% of cases. 270 MM patients from Johns Hopkins University (MD) and Weill Cornell Medicine (NY) had both FISH and MyPRS gene expression profiling performed between 2012 and 2016 using standard and previously published methodology, respectively. Results: Retrospective review of the matched FISH and MyPRS results showed: 25/28 (89%) patients wish FISH-identified t(4;14) were classified as MMSET (MS) subtype. 10/10 (100%) patients with t(14;16) or t(14;20) were classified as MAF-like (MF) subtype 62/67 (93%) patients with t(11;14) were assigned to the Cyclin D (1 or 2) subtype. Patients with FISH hyperdiploidy status were classified as the Hyperdiploid (HY) subtype or had multiple gains detected by the separate MyPRS Virtual Karyotype (VK) algorithm, included in MyPRS. TP53del was seen in patients with multiple molecular subtypes, predominantly Proliferation (PR) and MMSET (MS). Assessment of TP53 function by gene expression is a more clinically relevant prognostic marker than TP53del, as dysregulation of the tumor suppressor is affected by mutations as well as deletions. Analysis of the TP53 expression in the 39 patients with delTP53 showed a statistically significant difference, compared to patients without this deletion (P<0.0001). Conclusion: Gene expression profiling is a superior and more reliable method for determining an individual patients' prognostic risk status. The molecular subtypes of MM, as reported by Signal Genetics MyPRS assay, are driven by large-scale changes in gene expression caused by or closely associated with chromosomal changes, including translocations. Physicians who are managing myeloma patients and wishing to base their assessment of risk on R-ISS or mSMART Guidelines may obtain the required data points from either FISH or MyPRS, with the latter offering lower QNS rates, higher reproducibility, assessment of a larger number of cells and a substantially lower price point ($5,480 vs. $1,912; 2016 CMS data). A larger cohort study is now underway to further validate these observations. Figure GEP-based TP53 expression in patients with and without Del17p. P<0.0001 Figure. GEP-based TP53 expression in patients with and without Del17p. P<0.0001 Disclosures Van Laar: Signal Genetics, Inc.: Employment. Borrelo:Sidney Kimmel Cancer Institute: Employment. Jabalayan:Weill Cornell Medical Center: Employment. Niesvizky:Celgene: Consultancy, Research Funding, Speakers Bureau; Takeda: Consultancy, Research Funding, Speakers Bureau; Onyx: Consultancy, Research Funding, Speakers Bureau. Zielinski:Signal Genetics, Inc.: Employment. Leigh:Signal Genetics, Inc.: Employment. Brown:Signal Genetics, Inc.: Employment. Bender:Signal Genetics, Inc.: Employment.

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