Reduction of Tumor Burden Rather Than Off-Target Effects Drives Changes in T-Cell Number and Profile during Prolonged Ibrutinib Treatment in Relapsed or Refractory Chronic Lymphocytic Leukemia Patients
In this study, we analyzed the changes occurring in the peripheral blood mononuclear cells (PBMC) during long-term treatment with the Bruton's tyrosine kinase inhibitor ibrutinib in relapsed or refractory (R/R) chronic lymphocytic leukemia (CLL) patients (pts). PBMC populations were assessed by flow-cytometry including CLL cells, Natural Killer (NK) cells, T-cell memory subsets, helper subpopulations (Ths) and regulatory T cell (Tregs) subsets. Peripheral blood samples were collected before start of treatment and at week (wk) 4, 10, 16, 22 and at 8, 12, 24 and 36 months (mo) of treatment.Eleven pts were included in the stu...
Source: Blood - November 21, 2018 Category: Hematology Authors: Palma, M., Heimersson, K., Mulder, T. A., Nasman-Glaser, B., Osterborg, A., Mellstedt, H. Tags: 642. CLL: Therapy, excluding Transplantation: Poster III Source Type: research

Dual Inhibition of PI3K-{delta} and PI3K-{gamma} By Duvelisib Eliminates CLL B Cells, Impairs CLL-Supporting Cells, and Overcomes Ibrutinib Resistance in a Patient-Derived Xenograft Model
In conclusion, DUV inhibits the in vivo survival and proliferation of leukemic B cells from CLL patients, including those who have progressed on ibrutinib. Dual PI3K- and - inhibition is more effective at inhibiting CLL B cells in vivo than PI3K- inhibition alone. Moreover, PI3K- inhibition shifts macrophage polarization away from a CLL-supportive M2 phenotype. Thus, DUV exerts inhibitory effects on CLL B cells and on CLL-supporting T and myeloid cells. Overall, these findings elucidate the non-redundant roles of PI3K- and - in CLL and demonstrate the potent antitumor activity of dual PI3K isoform inhibition by DUV in ibru...
Source: Blood - November 21, 2018 Category: Hematology Authors: Chen, S.-S., Kutok, J. L., Ferrer, G., Ravichandran, P., Ibrahim, M., Kieso, Y., Barrientos, J. C., Weaver, D. T., Pachter, J. A., Rai, K. R., Chiorazzi, N. Tags: 642. CLL: Therapy, excluding Transplantation: Poster III Source Type: research

Tocilizumab to Prevent Infusion-Related Events in Patients with Chronic Lymphocytic Leukemia and Co-Morbidities Treated with Obinutuzumab and Chlorambucil: Results from the Randomized Phase Ib GALACTA Trial
Conclusions: Preliminary results suggest that use of a single 8mg/kg dose of TCZ prior to the first dose of G was feasible, but did not appear to prevent IRRs in this pt population. The study was primarily designed to assess the safety of the combination, and was underpowered to detect meaningful differences between groups in IRR severity. TCZ-treated pts who developed IRRs had higher baseline risk than those who did not, and the TCZ dose may have been insufficient, resulting in the lack of efficacy. Whether inhibition of this pro-survival cytokine enhances the cytotoxic potential of the regimen is not yet determined; upda...
Source: Blood - November 21, 2018 Category: Hematology Authors: Freeman, C. L., Bottcher, S., De la Serna, J., Delgado, J., Falzetti, F., Gobbi, M., Lejniece, S., Di Bernardo, M. C., Mallalieu, N. L., Nielsen, T., Knapp, A., Gribben, J. G. Tags: 642. CLL: Therapy, excluding Transplantation: Poster III Source Type: research

Factors That Influence Treatment Decision-Making: Perspectives of 1147 Chronic Lymphocytic Leukemia (CLL) Patients in the United States
Introduction: Given the availability of several active treatment (tx) options for CLL, providers frequently make tx recommendations based on their interpretation of objective data from consensus criteria and clinical trials. There are limited data describing patient (pt) experience, values, and insights when encountering multiple tx choices. The CLL Society, a pt-driven, physician-curated nonprofit organization focused on the unmet needs of the CLL community, sought to explore how CLL pts make tx decisions.Methods: A 64 question survey was distributed online and in paper to CLL pts from Oct-Dec 2017. The survey was develop...
Source: Blood - November 21, 2018 Category: Hematology Authors: Koffman, B., Dennison, B., Kennard, K., Byrd, J. C., Furman, R. R., Pagel, J. M., Davids, M. S., Nabhan, C., Kay, N. E., Siddiqi, T., Brander, D. M., Wierda, W. G., Stephens, D. M., Hill, B. T., Pinilla Ibarz, J., Cheson, B., Rosen, S. T., Awan, F. T., Ch Tags: 641. CLL: Biology and Pathophysiology, excluding Therapy: Poster III Source Type: research

Adverse Events, Patterns of Tumor Lysis Syndrome Prophylaxis and Management, and Dosing Patterns in a Large Cohort of Venetoclax Treated CLL Patients in Community and Academic Settings
This study represents a collaboration between US centers, CLL Collaborative Study of Real World Evidence (CORE), and UK CLL Forum. Demographics, baseline disease characteristics, Ven dosing, TLS risk (per FDA Ven label) and prophylaxis, and AEs were collected. Lab vs. clinical TLS was defined by Howard criteria. PFS was estimated by Kaplan Meier methodology. All comparisons were descriptive.Results: Of the 297 pts examined, median age at Ven initiation was 67 (range 37-91). The group was 69% male, 96% had R/R CLL, and 45% had del17p. Baseline characteristics stratified by practice setting are included in Table 1. 80% recei...
Source: Blood - November 21, 2018 Category: Hematology Authors: Roeker, L. E., Fox, C. P., Eyre, T. A., Allan, J. N., Schuster, S. J., Nabhan, C., Hill, B. T., Shah, N. N., Lansigan, F., Yazdy, M., Lamanna, N., Cheson, B., Singavi, A. K., Coombs, C. C., Barr, P., Skarbnik, A. P., Shadman, M., Tuncer, H. H., Ujjani, C. Tags: 641. CLL: Biology and Pathophysiology, excluding Therapy: Poster III Source Type: research

Serum IgM/Fcmr Interactions Inhibit BCR Signaling and Influence the Cinical Course of CLL
CLL cases display heterogeneous responses to B cell receptor (BCR) engagement which correlate with clinical course and survival. Typically, cases with more aggressive disease show greater activation of downstream signaling molecules, such as the kinases SYK, AKT and ERK, upon BCR engagement. The heterogeneous BCR signaling responses have been attributed to varying levels of anergy occurring as a consequence of chronic antigen engagement in the absence of T cell help. However, an alternative explanation for the anergic phenotype is that it is induced by binding of serum IgM to the high-affinity Fcμ receptor (FCMR), which...
Source: Blood - November 21, 2018 Category: Hematology Authors: Gobessi, S., Laurenti, L., Porro, F., Martines, C., Fazio, R., Xerxa, E., Innocenti, I., Zucchetto, A., Chen, S.-S., Yan, X.-J., Chiorazzi, N., Gattei, V., Efremov, D. G. Tags: 641. CLL: Biology and Pathophysiology, excluding Therapy: Poster III Source Type: research

Activated CLL B Cells Variably Modulate microRNA-155 Levels in Naive CD4+ T Cells, and the Direction and Magnitude of microRNA-155 Change Correlates with Th17 Levels and Clinical Course
T-helper 17 (Th17) cells constitute a subset of T cells that characteristically secrete IL-17. In addition to their normal adaptive immune functions, Th17 cells also play roles in supporting dysfunctional immune responses found in autoimmunity and cancer. Several studies suggest that Th17 cells play a protective role in chronic lymphocytic leukemia (CLL). For example, CLL patients exhibit varied levels of circulating Th17 cells, and elevated levels positively correlate with better clinical outcome regardless of IGHV-mutation status. To understand this relationship and elucidate the cellular and molecular mechanisms of Th17...
Source: Blood - November 21, 2018 Category: Hematology Authors: Jung, B., Ferrer, G., Chiu, P. Y., Aslam, R., Palacios, F., Sherry, B., Chiorazzi, N. Tags: 641. CLL: Biology and Pathophysiology, excluding Therapy: Poster III Source Type: research

Variable Bruton Tyrosine Kinase (BTK) Resynthesis across Patients with Chronic Lymphocytic Leukemia (CLL) on Acalabrutinib Therapy Affect Target Occupancy and Reactivation of B-Cell Receptor (BCR) Signaling
Inhibitors of B-cell receptor (BCR) signaling, in particular of Bruton tyrosine kinase (BTK), are effective in patients with chronic lymphocytic leukemia (CLL). Acalabrutinib is a highly selective, covalent BTK inhibitor with rapid absorption and fast elimination (Barf et al., J Pharmacol Exp Ther 2017; 363:240-252). In a previous clinical trial of patients with relapsed/refractory CLL, acalabrutinib therapy was well tolerated and efficacious and had high target occupancy (Byrd et al., N Engl J Med 2016; 374:323-21). Here, we report on BTK occupancy, BTK resynthesis rates, and the relationship between BTK occupancy and BCR...
Source: Blood - November 21, 2018 Category: Hematology Authors: Alsadhan, A. A., Cheung, J., Gulrajani, M., Cook, E. M., Pittaluga, S., Davies-Hill, T., Izumi, R., Sun, C. C., Covey, T., Wiestner, A., Herman, S. E. M. Tags: 641. CLL: Biology and Pathophysiology, excluding Therapy: Poster III Source Type: research

Dynamic BH3 Profiling Predicts Patient Response and MRD Status in Chronic Lymphocytic Leukemia (CLL) Patients Undergoing Frontline Treatment with Kinase Inhibitor Plus FCR (KI+FCR)
ConclusionsEx vivo treatment of CLL cells with IBR or DUV leads to increased BCL-2 dependence, and the level of in vivo delta-priming for BCL-2 dependence predicts depth of response to KI+FCR based frontline therapy in CLL. Additional experiments are ongoing to better define the mechanism underlying the altered anti-apoptotic dependencies seen with KI therapy in CLL cells. DBP should be further evaluated for its potential as a clinical decision-making tool to identify those young, fit CLL patients who are the best candidates for frontline KI+FCR therapy and who may have a more favorable risk/benefit ratio from a novel agen...
Source: Blood - November 21, 2018 Category: Hematology Authors: Lehmberg, T. Z., Valentin, R., Fernandes, S. M., Brown, J. R., Davids, M. S. Tags: 641. CLL: Biology and Pathophysiology, excluding Therapy: Poster III Source Type: research

The Fully Human Anti-CD47 Antibody SRF231 Has Dual-Mechanism Antitumor Activity Against Chronic Lymphocytic Leukemia (CLL) Cells and Increases the Activity of Both Rituximab and Venetoclax
BackgroundCD47 is over-expressed by many tumor types and protects tumor cells from destruction via tumor-intrinsic and -extrinsic means. The fully human anti-CD47 monoclonal antibody (mAb) SRF231 has previously been shown to block the "don't eat me" CD47/signal regulatory protein alpha (SIRPα) interaction and induce macrophage-mediated phagocytic uptake of CD47-expressing tumor cells, either alone or in the presence of anti-CD20 mAb. Furthermore, SRF231 inhibited tumor growth in preclinical models of aggressive non-Hodgkin lymphoma (Holland P, et al. ASH 2016). Here, we explored the activity of SRF231 again...
Source: Blood - November 21, 2018 Category: Hematology Authors: Valentin, R., Peluso, M. O., Lehmberg, T. Z., Adam, A., Zhang, L., Armet, C. M., Guerriero, J. L., Lee, B. H., Palombella, V. J., Holland, P. M., Paterson, A. M., Davids, M. S. Tags: 641. CLL: Biology and Pathophysiology, excluding Therapy: Poster III Source Type: research

Correlations between Pre-Transplant Treatment and Bone Marrow Response with Post-Transplant Outcomes in Patients with Myelodysplastic Syndrome Undergoing Allogeneic Stem Cell Transplantation
Conclusions: Achievement of CR or hematological improvement (HI) prior to allogeneic transplant was associated with superior survival post-transplant, while marrow CR and cytogenetic response did not impact post-transplant survival any different than going into allogeneic transplant with stable disease/no response. IPSS R score at diagnosis was associated with inferior post-transplant survival. The presence of mutations in ASXL1, ETV6, EZH2, RUNX1 or TP53 genes prior to transplant did not appear to impact OS or RFS post-transplant, but the total numbers were small. Although CR or HI after pre-transplant treatment improved ...
Source: Blood - November 21, 2018 Category: Hematology Authors: Desai, P., Alshaibani, A., Wu, X., Lee, S., Hsu, J., Ritchie, E. K., Samuel, M., Mayer, S. A., Phillips, A. A., Gergis, U., Shore, T. B., Van Besien, K., Roboz, G. J. Tags: 637. Myelodysplastic Syndromes-Clinical Studies: Poster III Source Type: research

Prognostic Value of a New Clinically-Based Classification System in Patients with CMML Undergoing Allogeneic Hematopoietic Stem Cell Transplantation: A Retrospective Analysis of the EBMT Chronic Malignancies Working Party
Conclusions: Although performed on a limited number of patients, in this retrospective analysis we show that CMML patients categorized as MD-CMML according to the new clinically-based classification underwent allo-HSCT with a significantly higher proportion of CR and had a significantly better PFS in comparison to patients with overlap or proliferative characteristics.DisclosuresFinke: Neovii: Consultancy, Honoraria, Other: travel grants, Research Funding; Novartis: Consultancy, Honoraria, Other: travel grants, Research Funding; Riemser: Consultancy, Honoraria, Research Funding; Medac: Consultancy, Honoraria, Other: travel...
Source: Blood - November 21, 2018 Category: Hematology Authors: Onida, F., Sbianchi, G., Koster, L., Iacobelli, S., Dreger, P., Bornhauser, M., Kroger, N., Sierra, J., Socie, G., Cornelissen, J. J., Poire, X., Faber, E., Bourhis, J.-H., Finke, J., Passweg, J. R., Salmenniemi, U., Schouten, H. C., Beguin, Y., Martin, S Tags: 637. Myelodysplastic Syndromes-Clinical Studies: Poster III Source Type: research

Analysis of Genomic Predispositions to Sporadic Myeloid Neoplasms Mediated By DDX41 in Japan
In conclusion, we identified DDX41 germline risk variants among the Japanese population. Germline DDX41 variants were seen in a substantial fraction of Japanese patients with sporadic myeloid neoplasms. Found in the general Japanese population at very low frequencies, these risk alleles account for the largest germline risk for myeloid neoplasms. Somatic DDX41 mutations were common with a prominent mutational hotspot, almost exclusive found in patients with DDX41 risk alleles. Given the high prevalence of DDX41 germline variants and the late onset of associated MDS and sAML, their detection may help better manage patients ...
Source: Blood - November 21, 2018 Category: Hematology Authors: Takeda, J., Yoshida, K., Yoshizato, T., Shiraishi, Y., Okuno, Y., Kon, A., Kataoka, K., Chiba, K., Tanaka, H., Sanada, M., Ishiyama, K., Chiba, S., Asou, N., Miyazaki, Y., Naoe, T., Usuki, K., Miyawaki, S., Kamatani, Y., Momozawa, Y., Nagasaki, M., Miyano Tags: 637. Myelodysplastic Syndromes-Clinical Studies: Poster III Source Type: research

Pattern of Immune-Mediated Toxicities in Patients with Myelodysplastic Syndrome (MDS) Treated with Nivolumab and Ipilimumab
Conclusions: The toxicities observed in patients with MDS treated with nivolumab and ipilimumab are consistent with those previously reported with these agents in other patient populations. Therapy combining nivolumab and ipilimumab led to higher rates of dermatologic, hepatic, and cardiovascular toxicities. Patients treated in the combination arm more frequently required prolonged courses of systemic corticosteroids (>28 days), and only those who received ipilimumab required additional immunosuppressant therapy.DisclosuresDaver: Karyopharm: Consultancy; BMS: Research Funding; Sunesis: Consultancy; Sunesis: Research Fun...
Source: Blood - November 21, 2018 Category: Hematology Authors: Rausch, C. R., Paul, S., Montalban Bravo, G., Jabbour, E. J., Daver, N. G., Alvarado, Y., DiNardo, C. D., Ravandi, F., Borthakur, G., Bose, P., Pemmaraju, N., Naqvi, K., Kornblau, S. M., Cortes, J. E., Kadia, T. M., Konopleva, M. Y., Ohanian, M. N., Pierc Tags: 637. Myelodysplastic Syndromes-Clinical Studies: Poster III Source Type: research

Planned Interim Analysis of a Phase 2 Study Evaluating the Combination of Pracinostat, a Histone Deacetylase Inhibitor (HDACi), and Azacitidine in Patients with High/Very High-Risk Myelodysplastic Syndrome (MDS)
Conclusions:The interim analysis of this study evaluating the efficacy and safety of pracinostat + azacitidine in patients with IPSS-R high-/very high-risk MDS revealed a discontinuation rate and an efficacy response rate meeting the predefined thresholds to allow for expansion of the study. These findings suggest that a reduced dose of pracinostat may allow patients to remain on treatment longer, thus increasing the likelihood of a treatment response. Based on these data, the study IDMC approved expansion of this study to enroll 60 evaluable patients. Updated data, including 6 months efficacy data on the initial cohort, w...
Source: Blood - November 21, 2018 Category: Hematology Authors: Keng, M. K., Khaled, S. K., Cooper, B., Warlick, E. D., Ramies, D., Mappa, S., Atallah, E. L. Tags: 637. Myelodysplastic Syndromes-Clinical Studies: Poster III Source Type: research

The Role of PPM1D Mutations in Lenalidomide Resistance and Progression in Patients with MDS and Deletion of Chromosome 5q
Conclusion: PPM1D mutations are recurrently found in MDS del(5q) patients at a frequency of 5.3% and may be coexpressed with TP53 mutations in 5q- MDS/AML cells. Frequency at resistance/AML progression was 18% for PPM1D and 53% for TP53 mutated patients, respectively. Our findings indicate an association of PPM1D mutations in addition to the previously described TP53 mutations with lenalidomide resistance and AML progression.DisclosuresMeggendorfer: MLL Munich Leukemia Laboratory: Employment. Krönke: Celgene: Honoraria. Haferlach: MLL Munich Leukemia Laboratory: Employment, Equity Ownership. Thiede: Novartis: Honorari...
Source: Blood - November 21, 2018 Category: Hematology Authors: Panagiota, V., Meggendorfer, M., Kubasch, A. S., Gabdoulline, R., Kronke, J., Shahswar, R., Mies, A., Kandziora, C., Klement, P., Schiller, J., Gohring, G., Haferlach, C., Ganster, C., Shirneshan, K., Gutermuth, A., Thiede, C., Germing, U., Schroeder, T., Tags: 637. Myelodysplastic Syndromes-Clinical Studies: Poster III Source Type: research

The Impact of Clonal Hematopoiesis of Indeterminate Potential on Survival in Patients with Newly Diagnosed Acute Myeloid Leukemia
Introduction:Clearance of detected somatic mutations at complete response by next-generation sequencing is a prognostic marker for survival in patients with acute myeloid leukemia (AML). However, the impact of allelic burden and persistence of clonal hematopoiesis of indeterminate potential (CHIP)-associated mutations on survival remains unclear. The aim of this study is to evaluate the prognostic impact of allelic burden of CHIP mutations at diagnosis, and their persistence within 6 months of therapy.Methods:From February 1, 2012 to May 26, 2016, we reviewed 562 patients with newly diagnosed AML. Next-generation sequencin...
Source: Blood - November 21, 2018 Category: Hematology Authors: Sasaki, K., Kanagal-Shamanna, R., Montalban-Bravo, G., Assi, R., Naqvi, K., Alfonso Pierola, A., Yilmaz, M., Short, N. J., Jabbour, E. J., Ravandi, F., Kadia, T. M., Pierce, S. A., Takahashi, K., DiNardo, C. D., Nogueras Gonzalez, G. M., Abaza, Y., Devend Tags: 637. Myelodysplastic Syndromes-Clinical Studies: Poster III Source Type: research

SLAMF7high CD16negative Monocytes Increase in Peripheral Blood of Patients with Myelofibrosis in Correlation with JAK2V617F Mutation
IntroductionMyelofibrosis (MF) occurrence can be attributed to various pathogenic mechanisms. A recent study showed that the neoplastic clone of fibrocytes (spindle shaped, fibroblast-like blood cells derived from monocyte lineage) was essential in primary MF pathogenesis; moreover, serum amyloid P (PRM-151), which suppresses fibrocyte differentiation, markedly improved survival and MF in a murine xenograft model (J Exp Med 2016; 213: 1723). Using a romiplostim-induced murine MF model, direct induction of fibrocyte differentiation using TPO receptor activation, leading to MF progression, was demonstrated (Leukemia 2017; 31...
Source: Blood - November 21, 2018 Category: Hematology Authors: Maekawa, T., Kato, S., Okada, Y., Tachi, N., Teramoto, M., Kawamura, T., Osawa, Y., Kobayashi, S., Sato, K., Hashimoto, M., Suzu, S., Usuki, K., Morishita, S., Araki, M., Komatsu, N., Kimura, F. Tags: 635. Myeloproliferative Syndromes: Basic Science: Poster III Source Type: research

Myeloproliferative Neoplasm (MPN) Driver Mutations Are Enriched during Hematopoietic Stem Cell Differentiation in Patterns That Correlate with Clinical Phenotype and Treatment Response
Conclusion. The pattern of clonal enrichment of an MPN stem cell during hematopoiesis is unique to individual pts and varies significantly among the 3 major WHO subtypes of PV, ET, and PMF. This pattern also differs in relation to the disease stage, and is informative of treatment effects. WB VAF does not predict the proportion of immature HSPC harboring driver mutation. For these reasons, evaluating the clonal heterogeneity of MPN driver mutations, particularly those in HSPCs, may provide a useful surrogate measure to qualify response to novel agents in pre-clinical and clinical studies in MPNs. This is currently being te...
Source: Blood - November 21, 2018 Category: Hematology Authors: Abu-Zeinah, G., Di Giandomenico, S., Sosner, C., Savage, N., Krichevsky, S., Ritchie, E. K., Kermani, P., Silver, R. T., Scandura, J. Tags: 635. Myeloproliferative Syndromes: Basic Science: Poster III Source Type: research

Impact of Myeloproliferative Neoplasms (MPNs) on Health-Related Quality of Life (HRQOL) and Medical Resource Utilization: Results from the MERGE Registry
BackgroundThe Philadelphia chromosome–negative classical MPNs (myelofibrosis [MF], polycythemia vera [PV], and essential thrombocythemia [ET]) are associated with a pronounced symptom burden, including fatigue, night sweats, itching, and inactivity that may affect patients' HRQOL. There is a limited real-world evidence from many of the Asian countries, including Middle East, regarding the impact of MPNs on HRQOL, or the economic burden associated with these diseases. MERGE is a multinational, multicenter, nonintervention study conducted in adult patients with MPNs in Asia, including Middle East, Turkey, and Algeria. ...
Source: Blood - November 21, 2018 Category: Hematology Authors: Taher, A., Yassin, M. A., Xiao, Z., Hou, H.-A., Tuglular, T., Mathews, V., Rippin, G., Sadek, I., Siddiqui, A., Wong, R. S. Tags: 634. Myeloproliferative Syndromes: Clinical: Poster III Source Type: research

Increased Frequency of IDH1/2 Mutations in Extramedullary Acute Myeloid Leukemia
ConclusionOverall, EM-AML patients had targetable mutations (i.e. IDH1/IDH2/FLT3) in 40% of cases with an increased frequency of IDH1/2 mutations (31%) in comparison to the general AML population. IDH mutant EM-AML patients achieved clinical benefit to specific inhibitors. These data support mutational analysis of EM-AML patients in order to personalize therapeutic options for our patients.Figure 1.DisclosuresBhagat: Genoptix: Employment. Watts: Takeda: Research Funding; Jazz Pharma: Consultancy, Speakers Bureau. Sweet: Novartis: Consultancy, Honoraria, Speakers Bureau; Novartis: Consultancy, Honoraria, Speakers Bureau; Ja...
Source: Blood - November 21, 2018 Category: Hematology Authors: Knepper, T. C., Deutsch, Y. E., Bhagat, C. K., Watts, J. M., Bradley, T. J., Samra, W., Hussaini, M. O., Sweet, K. L., Talati, C., Padron, E., Komrokji, R. S., Lancet, J. E., Sallman, D. A. Tags: 617. Acute Myeloid Leukemia: Biology, Cytogenetics, and Molecular Markers in Diagnosis and Prognosis: Poster I Source Type: research

EZH2 Mutations and Impact on Clinical Outcome Analyzed in 1604 Patients with Acute Myeloid Leukemia
ConclusionEZH mutations are recurrent alterations in patients with AML. The association with certain clinical factors and typical mutations such as RUNX1 and ASXL1 points to the fact that these mutations are associated with secondary AML. Our data do not indicate that EZH2 mutations represent an independent prognostic factor.DisclosuresMiddeke: Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees. Rollig: Bayer: Research Funding; J...
Source: Blood - November 21, 2018 Category: Hematology Authors: Stasik, S., Middeke, J. M., Kramer, M., Rollig, C., Kramer, A., Scholl, S., Hochhaus, A., Crysandt, M., Brummendorf, T. H., Naumann, R., Steffen, B., Kunzmann, V., Einsele, H., Schaich, M., Burchert, A., Neubauer, A., Schafer-Eckart, K., Schliemann, C., K Tags: 617. Acute Myeloid Leukemia: Biology, Cytogenetics, and Molecular Markers in Diagnosis and Prognosis: Poster I Source Type: research

Molecular Detection of Minimal Residual Disease Precedes Morphological Relapse and Could be Used to Identify Relapse in Pediatric and Young Adult B-Cell Acute Lymphoblastic Leukemia Patients Treated with Tisagenlecleucel
ConclusionsTo examine the comparability of flow cytometry and Ig NGS methods in assessing MRD, baseline and post-treatment samples were tested. Baseline samples, which had a high disease burden, showed 100% MRD concordance between both assays. However, post-treatment, where the leukemic burden was dramatically reduced, Ig NGS detected a greater number of MRD positive samples compared to FC, at each sensitivity level tested (10-4, 10-5 and 10-6). At the highest sensitivity level of 10-6, Ig NGS was able to detect 18% more MRD positive post-treatment samples. Importantly, Ig NGS was able to detect MRD positivity 1-4 months a...
Source: Blood - November 21, 2018 Category: Hematology Authors: Pulsipher, M. A., Han, X., Quigley, M., Kari, G., Rives, S., Laetsch, T. W., Myers, G. D., Hiramatsu, H., Yanik, G. A., Qayed, M., Driscoll, T., Boyer, M. W., Stefanski, H., Buchner, J., Baruchel, A., Bader, P., Yi, L., Kalfoglou, C., Robins, H., Yusko, E Tags: 618. Acute Lymphoblastic Leukemia: Biology, Cytogenetics, and Molecular Markers in Diagnosis and Prognosis: Poster I Source Type: research

Ultrasensitive Duplex Sequencing of Pretreatment ABL1 Kinase Domain Mutations in Patients with Newly Diagnosed Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia
Conclusions: DS identified very low level pretreatment ABL1 KD mutations in a majority of pts with newly diagnosed Ph+ ALL but these appear inconsequential. Ninety percent of mutations identified have not been described as resistance mutations, suggesting that they may be either synonymous or functionally neutral amino acid changes resulting from normal aging. There was no apparent association of these mutations and risk of relapse, even in the minority of cases in which known resistance mutations were detected at baseline. These data suggest that pretreatment testing for ABL1 KD mutations in Ph+ ALL is unlikely to affect ...
Source: Blood - November 21, 2018 Category: Hematology Authors: Short, N. J., Kantarjian, H. M., Sasaki, K., Ravandi, F., Cortes, J. E., Konopleva, M. Y., Issa, G. C., Kanagal-Shamanna, R., Kornblau, S. M., Garcia-Manero, G., Rivera, V., Garris, R. E., Salk, J., Prichard, J., Radich, J. P., Jabbour, E. J. Tags: 618. Acute Lymphoblastic Leukemia: Biology, Cytogenetics, and Molecular Markers in Diagnosis and Prognosis: Poster I Source Type: research

ZNF384-Fusion Proteins Have High Affinity to EP300, Which Increases Their Transcriptional Activities
ZNF384 fusion (Z-fusion) genes are recently identified recurrent fusion genes of B-acute lymphoblastic leukemia (ALL) and cause differentiation block of B-cells; however, its molecular mechanisms have yet to be clarified. Common structural character of Z-fusion proteins is that fusion partners are fused to the N-terminal end of full-length ZNF384 (Figure 1A), suggesting that protein-fusions confer specific transcriptional targets on ZNF384. We searched Z-fusion-specific transcriptional targets that could cause differentiation block of B-cells by analyzing the data of gene expression profile of 54 primary B-ALL samples cont...
Source: Blood - November 21, 2018 Category: Hematology Authors: Yamamoto, H., Hayakawa, F., Yasuda, T., Minamikawa, Y., Tange, N., Hirano, D., Kojima, Y., Morishita, T., Tsuzuki, S., Mano, H., Naoe, T., Kiyoi, H. Tags: 618. Acute Lymphoblastic Leukemia: Biology, Cytogenetics, and Molecular Markers in Diagnosis and Prognosis: Poster I Source Type: research

Prognostic Factors, Outcomes and Clinical Characteristics in Patients with Transformed Follicular Lymphoma (t-FL): Cohort Study of 172 Patients
In this study we have analysed the clinical characteristics, prognostic factors, treatments and survival outcome of pts with pathologically confirmed t-FL.Methods: We reviewed pts with low grade lymphoma who developed a subsequent aggressive B-cell lymphoma at MDACC from 7/1998 to 07/2017. Transformation was defined as development of an aggressive lymphoma in the setting of a prior diagnosis of low grade NHL. Pts with composite histology or grade IIIb FL at dx were excluded. We identified a total of 273 pts who transformed from a low grade lymphoma, including 172 with an initial diagnosis of FL (63%), MZL (18%), and SLL (1...
Source: Blood - November 21, 2018 Category: Hematology Authors: Jain, P., Nastoupil, L. J., Kanagal-Shamanna, R., Nogueras Gonzalez, G. M., Noorani, M., Romaguera, J. E., Fayad, L., Samaniego, F., Westin, J. R., Medeiros, L. J., Neelapu, S., Wang, M., Fowler, N. H. Tags: 623. Mantle Cell, Follicular, and Other Indolent B-Cell Lymphoma-Clinical Studies: Poster I Source Type: research

Clinical and Genomic Characteristics in De Novo Blastoid/Pleomorphic (dnMCL) and Transformed Blastoid/Pleomorphic (t-MCL) Mantle Cell Lymphoma (MCL) in the Ibrutinib Era: Comprehensive Analysis of 168 Patients
Introduction: Patients (pts) with histologically aggressive MCL (HA-MCL; blastoid or pleomorphic) including [de novo (dnMCL) or those transformed from classic morphology (t-MCL)], exhibit a poor prognosis. This analysis provides a comprehensive assessment of so far the largest patient cohort with HA-MCL treated with various modalities.Methods: We included all HA-MCL pts [blastoid (n=142) or pleomorphic morphology (n=26)] at MD Anderson Cancer Center from 12/1997 to 07/2018. Among the 168 pts, 99 were dn-MCL and 69 were t-MCL. Pt characteristics were collected at the time of initial diagnosis in dnMCL and at transformation ...
Source: Blood - November 21, 2018 Category: Hematology Authors: Jain, P., Kanagal-Shamanna, R., Zhang, S., Ok, C. Y., Nogueras Gonzalez, G. M., Ahmed, M., Omarya, G.-P., Ghorab, A., Boddu, P. C., Chen, W., Lee, H. J., Badillo, M., Nomie, K., Fayad, L., Nastoupil, L. J., Champlin, R. E., Neelapu, S. S., Patel, K., Mede Tags: 623. Mantle Cell, Follicular, and Other Indolent B-Cell Lymphoma-Clinical Studies: Poster I Source Type: research

Obinutuzumab-Based Immunochemotherapy Prolongs Progression-Free Survival and Time to Next Anti-Lymphoma Treatment in Patients with Previously Untreated Follicular Lymphoma: Four-Year Results from the Phase III GALLIUM Study
Conclusions: In line with the PA, the results from this updated analysis of the GALLIUM study, with a median follow-up of almost 5 years, reinforce that G-chemo provides clinically meaningful improvements in outcomes relative to R-chemo in previously untreated FL pts. OS data remain immature, with additional follow-up needed to draw conclusions. Safety data are consistent with those reported in the PA.Figure 1.DisclosuresTownsend: Gilead: Consultancy; Roche: Consultancy. Buske: Roche: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Bayer: Research Funding. Cartron: Roche: Consultancy, Honoraria; Sanofi: ...
Source: Blood - November 21, 2018 Category: Hematology Authors: Townsend, W., Buske, C., Cartron, G., Cunningham, D., Dyer, M. J., Gribben, J. G., Hess, G., Ishikawa, T., Keller, U., Kneba, M., Malladi, R., Neidhart, J. D., Rusconi, C., Zhu, J., Catalani, O., Knapp, A., Zeuner, H., Herold, M., Hiddemann, W., Marcus, R Tags: 623. Mantle Cell, Follicular, and Other Indolent B-Cell Lymphoma-Clinical Studies: Poster I Source Type: research

Comparison of Efficacy and Safety of Biosimilar CT-P10 to Rituximab in Patients with Previously Untreated Low Tumor Burden Follicular Lymphoma (LTBFL): A Randomized Phase III Study
Background: CT-P10 is the first biosimilar to innovator rituximab (RTX) approved for all indications by the European Medicines Agency. The pharmacokinetics (PK) equivalence and non-inferior efficacy of CT-P10 compared with RTX in patients with newly diagnosed advanced follicular lymphoma (FL) was previously demonstrated when used with combination chemotherapy of cyclophosphamide, vincristine and prednisone (CVP) (Kim WS et al. 2017).Objectives: This is an ongoing, phase 3, randomized, double blind, active controlled study to demonstrate similarity of efficacy and safety between CT-P10 and RTX as monotherapy in patients wit...
Source: Blood - November 21, 2018 Category: Hematology Authors: Ogura, M., Sancho, J. M., Cho, S.-G., Nakazawa, H., Suzumiya, J., Tumyan, G., Kim, J. S., Lennard, A., Mariz, J. M., Ilyin, N., Jurczak, W., Martinez, A. L., Samoilova, O., Zhavrid, E., Ruiz, E. Y., Trneny, M., Popplewell, L., Coiffier, B., Buske, C., Kim Tags: 623. Mantle Cell, Follicular, and Other Indolent B-Cell Lymphoma-Clinical Studies: Poster I Source Type: research

Long-Term Efficacy and Safety from the Copanlisib CHRONOS-1 Study in Patients with Relapsed or Refractory Indolent B-Cell Lymphoma
Conclusions: Analysis of the 2-year follow up of patients with relapsed or refractory indolent B-cell lymphoma treated with copanlisib demonstrated a deepening of the responses with a conversion of 7 patients from PR to CR, durable responses and manageable AEs. Moreover, the benefit/risk ratio for copanlisib treatment remains favorable with no evidence of worsening of AEs for patients treated long-term.DisclosuresDreyling: Mundipharma: Consultancy, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Roche: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Acerta: ...
Source: Blood - November 21, 2018 Category: Hematology Authors: Dreyling, M., Santoro, A., Mollica, L., Leppa, S., Follows, G. A., Lenz, G., Kim, W. S., Nagler, A., Panayiotidis, P., Demeter, J., Ozcan, M., Kosinova, M., Bouabdallah, K., Morschhauser, F., Stevens, D., Trevarthen, D., Rodrigues, L., Hiemeyer, F., Wang, Tags: 623. Mantle Cell, Follicular, and Other Indolent B-Cell Lymphoma-Clinical Studies: Poster I Source Type: research

Seven Year Follow up and Comparison of Dosing Strategies from the Pivotal Phase II Clinical Trial of Lenalidomide Plus Rituximab (R2) in Previously Untreated Follicular Lymphoma
Conclusions: A combination of lenalidomide with rituximab produced durable responses in pts with FL. At a follow up of 7 years, the majority of pts remain in remission and patients who achieved CR had the best outcomes. Five year PFS may be longer in pts who received 12mo of therapy, but will need larger analysis to confirm. Further studies are ongoing to analyze mutation dynamics and genomic profile to identify molecular biomarkers.DisclosuresFowler: Janssen: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding. Nastoupil: Novartis: Honoraria; Juno: Honoraria; Gilead: Honoraria; TG Therappeutics: Re...
Source: Blood - November 21, 2018 Category: Hematology Authors: Fowler, N. H., Jain, P., Nastoupil, L. J., Hagemeister, F. B., Forbes, S. G., Lagrone, L., Fayad, L., Lee, H. J., Davis, R. E., Westin, J. R., Wang, M., Neelapu, S. S., Samaniego, F. Tags: 623. Mantle Cell, Follicular, and Other Indolent B-Cell Lymphoma-Clinical Studies: Poster I Source Type: research

Five-Year Outcomes of SWOG S1106: A Randomized Phase II US Intergroup Study of R-HCVAD Vs. R-Bendamustine Followed By Autologous Stem Cell Transplant for Patients with Mantle Cell Lymphoma
Conclusion: The optimal induction regimen prior to ASCT in the initial management of MCL is a source of significant debate. Our initial findings supported RB as an effective platform with the ability to achieve MRD negativity. Long-term results of this study continue to demonstrate excellent response rates, 5-yr PFS and 5-yr OS with either RH or RB without any new toxicity signal. The 5-yr outcomes with RB compare favorably to more aggressive cytarabine-based induction regimens. Thus, R-Bendamustine could be an excellent backbone for induction therapy in transplant eligible patients and needs to be tested in larger phase I...
Source: Blood - November 21, 2018 Category: Hematology Authors: Kamdar, M., Li, H., Chen, R. W., Rimsza, L. M., Leblanc, M. L., Fenske, T. S., Barr, P., Phillips, T. J., Leonard, J. P., Kahl, B. S., Friedberg, J. W., Smith, S. M. Tags: 623. Mantle Cell, Follicular, and Other Indolent B-Cell Lymphoma-Clinical Studies: Poster I Source Type: research

Updated Safety and Activity of the Investigational Bruton Tyrosine Kinase Inhibitor Zanubrutinib (BGB-3111) in Patients with Mantle Cell Lymphoma
Conclusions: Zanubrutinib monotherapy was demonstrated to be highly active in patients with relapsed/refractory MCL, with a safety profile consistent with that of previous reports of zanubrutinib.DisclosuresTam: Pharmacyclics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; BeiGene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory ...
Source: Blood - November 21, 2018 Category: Hematology Authors: Tam, C. S., Wang, M., Simpson, D., Opat, S., Cull, G., Munoz, J., Phillips, T. J., Kim, W.-S., Hilger, J., Huang, J., Novotny, W., Trotman, J. Tags: 623. Mantle Cell, Follicular, and Other Indolent B-Cell Lymphoma-Clinical Studies: Poster I Source Type: research

The Absolute Count of Lymphocytes Is a Strong Predictive Factor for Relapse/Regrowth Events and Outcomes in Patients with Regressive Methotrexate-Associated Lymphoproliferative Disorders
Conclusion] Our data suggest that the ALC is one of the predictive factors for R/R and OS in patients with regressive MTX-LPDs.DisclosuresTokuhira: Mitsubishi Tanabe Pharma Corporation: Speakers Bureau; AYUMI Pharmaceutical Corporation: Speakers Bureau; Bristol-Myers Squibb: Speakers Bureau; Chugai: Speakers Bureau. Tamaru: Nichirei Bioscience INC.: Research Funding; Takeda Pharmaceutical Company Limited: Speakers Bureau. Kizaki: Nippon Shinyaku,: Research Funding, Speakers Bureau; Celgene: Research Funding, Speakers Bureau; Bristol-Myers Squibb: Research Funding, Speakers Bureau; Novartis: Speakers Bureau. (Source: Blood)
Source: Blood - November 21, 2018 Category: Hematology Authors: Tokuhira, M., Kimura, Y., Tanaka, Y., Takahashi, Y., Tomikawa, T., Watanabe, J., Anan-Nemoto, T., Sagawa, M., Momose, S., Higashi, M., Takayuki, T., Nakaseko, R., Tamaru, J.-i., Kizaki, M. Tags: 622. Lymphoma Biology-Non-Genetic Studies: Poster I Source Type: research

Genomics of Limited-Stage Diffuse Large B-Cell Lymphoma Developing Late Relapse: Analysis of Gene Alterations in Paired Primary and Late Relapsed Tumors By Target Sequencing
Conclusions:Common characteristics shared in a subgroup of pts with limited-stage DLBCL who developed LR were as follows: non-GCB type, CD79B and/or MYD88 mutations, and extranodal disease at primary manifestation. The mechanisms of LR from the viewpoint of gene alterations were considered heterogeneous.DisclosuresMaruyama: Asahi Kasei Pharma: Honoraria; Takeda: Honoraria, Research Funding; Bristol-Myers Squibb: Honoraria; Dai-ichi-Sankyo: Honoraria; Dai-Nippon-Sumitomo: Honoraria; MSD: Honoraria, Research Funding; Chugai Pharma: Honoraria, Research Funding; Eisai: Honoraria, Research Funding; Fujifilm: Honoraria, Research...
Source: Blood - November 21, 2018 Category: Hematology Authors: Suzuki, T., Fukuhara, S., Nomoto, J., Yamashita, S., Maeshima, A. M., Ito, Y., Hatta, S., Yuda, S., Makita, S., Munakata, W., Suzuki, T., Maruyama, D., Taniguchi, H., Ushijima, T., Izutsu, K., Tobinai, K., Kobayashi, Y. Tags: 621. Lymphoma-Genetic/Epigenetic Biology: Poster I Source Type: research

The Presence of Defective Epstein-Barr Virus (EBV) Infection in Patients with EBV-Associated Hematological Malignancy
DiscussionAlthough the essential roles of several latency-associated genes, such as LMP-1 and EBNA-2, in EBV-mediated immortalization and transformation of human lymphocytes have long been discussed, our finding raises the possibility that lytic cycle-associated genes also contribute to lymphomagenesis. This agrees with reports that lytic cycle-associated genes are expressed in Burkitt lymphoma, DLBCL, and chronic active EBV infection, and that BZLF1-deficient lymphoblastoid cells exhibit significantly impaired tumorigenicity in mice. In addition, essential gene deletions lead to the protection of EBV-infected cells from l...
Source: Blood - November 21, 2018 Category: Hematology Authors: Okuno, Y., Murata, T., Sato, Y., Muramatsu, H., Ito, Y., Watanabe, T., Okuno, T., Murakami, N., Yoshida, K., Sawada, A., Inoue, M., Kawa, K., Seto, M., Ohshima, K., Shiraishi, Y., Chiba, K., Tanaka, H., Miyano, S., Narita, Y., Yoshida, M., Goshima, F., Ka Tags: 621. Lymphoma-Genetic/Epigenetic Biology: Poster I Source Type: research

Diverse Landscape of TET2 Variants in MDS and AML
INTRODUCTIONThe TET2 (Ten-Eleven Translocation 2) gene, located at chromosome 4q24.1, belongs to TET family of proteins that possesses the capacity of catalyzing the conversion of 5-methylcytosine into 5-hydroxymethylcytosine. It is considered to be a putative tumor suppressor gene during cancer initiation and development. TET2 mutations are extensively studied and reported in a variety of human hematological malignancies including acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), suggesting a crucial role of TET2 in the pathogenesis of blood cancers. The landscape of rare TET2 variants which may be of poten...
Source: Blood - November 21, 2018 Category: Hematology Authors: Tallis, E., Benton, C. B., Khan, A., Assi, R., DiNardo, C. D., Hornbaker, M. J., Major, C. K., Boddu, P., Kanagal-Shamanna, R., Patel, K. P., Daver, N. G., Takahashi, K., Montalban-Bravo, G., Kadia, T. M., Konopleva, M. Y., Andreeff, M., Kantarjian, H. M. Tags: 617. Acute Myeloid Leukemia: Biology, Cytogenetics, and Molecular Markers in Diagnosis and Prognosis: Poster I Source Type: research

Longitudinal Monitoring of AML Tumors with High-Throughput Single-Cell DNA Sequencing Reveals Rare Clones Prognostic for Disease Progression and Therapy Response
AML (acute myeloid leukemia) is increasingly being treated with precision medicine. To better inform treatment, the mutational content of patient samples must be determined. However, current tumor sequencing paradigms are inadequate to fully characterize many instances of the disease. A major challenge has been the unambiguous identification of potentially rare and genetically heterogeneous neoplastic cell populations, capable of critically impacting tumor evolution and the acquisition of therapeutic resistance. Standard bulk population sequencing is unable to identify rare alleles and definitively determine whether mutati...
Source: Blood - November 21, 2018 Category: Hematology Authors: Eastburn, D. J., McMahon, C. M., Durruthy-Durruthy, R., Carroll, M., Smith, C. C., Perl, A. E. Tags: 617. Acute Myeloid Leukemia: Biology, Cytogenetics, and Molecular Markers in Diagnosis and Prognosis: Poster I Source Type: research

Clinical Characteristics and Outcome in IDH1/2 Mutant AML Patients - Analysis of 3898 Newly Diagnosed Patients with Acute Myeloid Leukemia
PurposeMutations of the isocitrate dehydrogenase-1 (IDH1) and IDH2 genes are one of the most frequent alterations in acute myeloid leukemia (AML) and can be found in ~20% of patients at diagnosis. Several IDH inhibitors are currently in late stage clinical development with Enasidenib, an IDH2 inhibitor, being recently approved by the FDA. Previous analyses have reported differential impact on response to chemotherapy and outcome, depending on the IDH-mutation type, co-occurring mutations and cytogenetic abnormalities, as well as the variant allele frequency (VAF) of IDH mutations. In order to better understand its prognost...
Source: Blood - November 21, 2018 Category: Hematology Authors: Middeke, J. M., Rollig, C., Kramer, M., Kramer, A., Bochtler, T., Scholl, S., Hochhaus, A., Jost, E., Brummendorf, T. H., Naumann, R., Steffen, B., Kunzmann, V., Einsele, H., Schaich, M., Burchert, A., Neubauer, A., Schafer-Eckart, K., Schliemann, C., Kra Tags: 617. Acute Myeloid Leukemia: Biology, Cytogenetics, and Molecular Markers in Diagnosis and Prognosis: Poster I Source Type: research

Identification of TIM-3/Gal-9 Autocrine Loop As a Novel Wnt-Ligands Independent Machinery for the Constitutive Activation of Canonical Wnt Pathway in AML-LSCs
We originally identified T-cell immunoglobulin mucin-3 (TIM-3) as a leukemic stem cells (LSCs)-specific surface molecule and a useful marker for discriminating LSCs from hematopoietic stem cells (HSCs). Furthermore, we recently identified an unique autocrine loop composed of TIM-3 and its ligand galectin-9 (Gal-9). This TIM-3/Gal-9 autocrine loop enhances self-renewal capacity of AML-LSCs and contributes to leukemia progression(Kikushige et al., Cell Stem Cell 2015).To clarify the molecular mechanism how TIM-3 signaling enhances stem cell properties of AML-LSCs, we performed shRNA-mediated knock-down(KD) of TIM-3 in KASUMI...
Source: Blood - November 21, 2018 Category: Hematology Authors: Sakoda, T., Kikushige, Y., Miyamoto, T., Akashi, K. Tags: 617. Acute Myeloid Leukemia: Biology, Cytogenetics, and Molecular Markers in Diagnosis and Prognosis: Poster I Source Type: research

Impact of Minimal Residual Disease and Achievement of Complete Remission/Complete Remission with Partial Hematologic Recovery (CR/CRh) on Overall Survival Following Treatment with Gilteritinib in Patients with Relapsed/Refractory (R/R) Acute Myeloid Leukemia (AML) with FLT3 Mutations
Background: Gilteritinib, a highly selective fms-like tyrosine kinase 3 (FLT3)/AXL inhibitor, demonstrated strong antileukemic activity at doses ≥80 mg/day in patients with R/R AML with FLT3 mutations (FLT3mut+) enrolled in the CHRYSALIS phase 1/2 study (NCT02014558). We analyzed the impact of minimal residual disease (MRD) and achievement of complete remission/complete remission with partial hematologic recovery (CR/CRh) on overall survival (OS) in patients with FLT3mut+ R/R AML from the CHRYSALIS study.Methods: Minimal residual disease was assessed by next-generation sequencing (NGS) using an Illumina® sequencing ...
Source: Blood - November 21, 2018 Category: Hematology Authors: Levis, M. J., Perl, A. E., Altman, J. K., Cortes, J. E., Smith, C. C., Baer, M. R., Claxton, D. F., Jurcic, J. G., Ritchie, E. K., Strickland, S. A., Tibes, R., Hill, J. E., Rosales, M., Bahceci, E. Tags: 616. Acute Myeloid Leukemia: Novel Therapy, excluding Transplantation: Poster I Source Type: research

Intratumoral Injection of CpG-ODN Plus Systemic Ibrutinib Induces an Anti-Tumor Immune Response Affecting T Cell Subsets in the Microenvironment of Both Injected and Non-Injected Tumor Sites in Patients with Low-Grade Lymphoma
CONCLUSION: CpG is known to activate antigen-presenting cells such as dendritic cells and macrophages. Ibrutinib is a small molecule that has been shown to have direct anti-tumor effects in B cell lymphoma and may skew an immune response towards that of a TH1 type. Here we show that together, they can effect changes in the tumor microenvironment in both treated and in untreated sites of disease.This clinical trial is ongoing and open to accrual.DisclosuresKhodadoust: Innate Pharma: Research Funding. (Source: Blood)
Source: Blood - November 21, 2018 Category: Hematology Authors: Czerwinski, D. K., Frank, M. J., Shree, T., Khodadoust, M. S., Long, S. R., Levy, R. Tags: 623. Mantle Cell, Follicular, and Other Indolent B-Cell Lymphoma-Clinical Studies: Poster I Source Type: research

Outcomes for Patients with Pre-Existing Diabetes or Hypertension Treated with Copanlisib from the CHRONOS-1 Study in Patients with Relapsed or Refractory Indolent B-Cell Lymphoma
Conclusions: These results support use of copanlisib in indolent lymphoma patients with well-controlled diabetes or hypertension. In particular, the transient hyperglycemia in diabetic patients did not exacerbate metabolic status as reflected in HbA1c values. Thus, patients with these pre-existing conditions should not be precluded treatment a priori.DisclosuresZinzani: Celltrion: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Merck: Honoraria, Membership on an entity's Board of Directors or advisory committees; TG Pharmaceuticals: Honoraria, Membership on an entity's Board...
Source: Blood - November 21, 2018 Category: Hematology Authors: Zinzani, P. L., Santoro, A., Mollica, L., Leppa, S., Follows, G. A., Lenz, G., Kim, W. S., Nagler, A., Panayiotidis, P., Demeter, J., Morschhauser, F., Rodrigues, L., Reeves, J., Hiemeyer, F., Miriyala, A., Garcia-Vargas, J., Childs, B. H., Dreyling, M. H Tags: 623. Mantle Cell, Follicular, and Other Indolent B-Cell Lymphoma-Clinical Studies: Poster I Source Type: research

Similar Efficacy and Safety of CT-P10 and Reference Rituximab in Patients with Advanced Stage Follicular Lymphoma: Updated Phase III Study Results
Conclusion: At the median follow-up duration of 23 months, the updated efficacy data in advanced FL patients demonstrated comparable PFS, sustained response and OS between CT-P10 and RTX. CT-P10 was also well tolerated and its safety profile was similar to that of RTX. The updated safety results did not reveal any trends or new signals noted in the patients treated with CT-P10.DisclosuresKim: Mundipharma: Research Funding; Novartis: Research Funding; Kyowa-Kirin: Research Funding; Celltrion: Research Funding; Roche: Research Funding; J&J: Research Funding; Takeda: Research Funding. Buske: Roche: Honoraria, Research Fun...
Source: Blood - November 21, 2018 Category: Hematology Authors: Kim, W.-S., Buske, C., Kwak, L. W., Ogura, M., Coiffier, B., Lee, S., Kim, S. Tags: 623. Mantle Cell, Follicular, and Other Indolent B-Cell Lymphoma-Clinical Studies: Poster I Source Type: research

Efficacy of Mogamulizumab By Prior Systemic Therapy in Patients with Previously Treated Cutaneous T-Cell Lymphoma: Post Hoc Analysis from the Phase 3 Mavoric Study
Aims: Patients with the cutaneous T-cell lymphoma subtypes mycosis fungoides (MF) and Sézary syndrome (SS) often require multiple lines and types of systemic therapy. The phase 3 MAVORIC study (NCT01728805) showed that mogamulizumab (MOGA), a monoclonal antibody directed against C-C chemokine receptor 4 (CCR4), is superior to vorinostat (VORI) in median progression-free survival (PFS; 7.7 vs 3.1 months, P
Source: Blood - November 21, 2018 Category: Hematology Authors: Zinzani, P. L., Horwitz, S. M., Kim, Y. H., Moskowitz, A. J., Porcu, P., Scarisbrick, J., Leoni, M., Dwyer, K., Sun, W., Nikonova, E., Bagot, M. Tags: 624. Hodgkin Lymphoma and T/NK Cell Lymphoma-Clinical Studies: Poster I Source Type: research

Preliminary Results of the Stapled Peptide ALRN-6924, a Dual Inhibitor of MDMX and MDM2, in Two Phase IIa Dose Expansion Cohorts in Relapsed/Refractory TP53 Wild-Type Peripheral T-Cell Lymphoma
Conclusion: ALRN-6924 has shown activity against PTCL and has an acceptable safety profile across QW and TIW dosing. The potential for pseudoprogression was not initially recognized, hence raising the possibility that the true response rate for QW may be higher. These early data support continued development of ALRN-6924 for the treatment of PTCL.DisclosuresShustov: Seattle Genetics: Research Funding. Horwitz: Celgene: Consultancy, Research Funding; Forty Seven: Consultancy, Research Funding; Infinity/Verastem: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; Mundipharma: Consultancy; Kyowa-H...
Source: Blood - November 21, 2018 Category: Hematology Authors: Shustov, A. R., Horwitz, S. M., Zain, J., Patel, M. R., Goel, S., Sokol, L., Meric-Bernstam, F., Shapiro, G., Dwivedy Nasta, S., Janakiram, M., Weinstock, D. M., Korn, R., Payton, M., Annis, D. A., Pinchasik, D., Aivado, M., Mehta, A. Tags: 624. Hodgkin Lymphoma and T/NK Cell Lymphoma-Clinical Studies: Poster I Source Type: research

Circulating Lymphoma Cells in Mycosis Fungoides/Sezary Syndrome Show Heterogeneity of the Cell-of-Origin and Variable PD-1 Expression By Flow Cytometric Analysis
Conclusions: Lymphoma cells in MF/SS show marked heterogeneity of expression of PD-1 including clear subset arising from TFH. This suggests MF/SS may represent multiple biological entities. Further studies will be necessary to investigate the clinical significance of cell-of-origin of MF/SS.DisclosuresYabe: Y-mAbs Therapeutics: Consultancy. Moskowitz: ADC Therapeutics: Research Funding; Incyte: Research Funding; Bristol Myers-Squibb: Consultancy, Research Funding; Takeda: Honoraria; Merck: Research Funding; Seattle Genetics: Consultancy, Honoraria, Research Funding. Horwitz: Infinity/Verastem: Consultancy, Research Funding...
Source: Blood - November 21, 2018 Category: Hematology Authors: Yabe, M., Lewis, N., Gao, Q., Sigler, A., Baik, J., Pulitzer, M., Myskowski, P., Moskowitz, A. J., Horwitz, S. M., Dogan, A., Roshal, M. Tags: 624. Hodgkin Lymphoma and T/NK Cell Lymphoma-Clinical Studies: Poster I Source Type: research

Checkpoint Blockade Therapy May Sensitize Hodgkin Lymphoma to Subsequent Therapy
Background: Relapsed or refractory (R/R) Hodgkin lymphoma (HL) remains a significant clinical problem. Recently checkpoint blockade therapy (CBT) has shown striking activity in this setting, but the complete response (CR) rate is modest. Patients who relapse after CBT have limited therapeutic options. A prior, retrospective study showed that after anti-PD-1 therapy the objective response rate to chemotherapy alone was 61% (Rossi et al 2017). We investigated the effect of treatment subsequent to CBT in a large international multicenter retrospective analysis.Methods: Seventeen centers across the US and Canada are participat...
Source: Blood - November 21, 2018 Category: Hematology Authors: Carreau, N. A., Pail, O., Armand, P., Merryman, R. W., Advani, R. H., Spinner, M. A., Herrera, A. F., Chen, R. W., Tomassetti, S., Ramchandren, R., Hamid, M., Assouline, S., Santiago, R., Wagner-Johnston, N. D., Paul, S., Svoboda, J., Bair, S. M., Barta, Tags: 624. Hodgkin Lymphoma and T/NK Cell Lymphoma-Clinical Studies: Poster I Source Type: research

Argx-110 for Treatment of CD70-Positive Advanced Cutaneous T-Cell Lymphoma in a Phase 1/2 Clinical Trial
ConclusionsARGX-110 was safe and well tolerated at both dose levels (1 and 5 mg/kg) in advanced CD70-expressing CTCL patients. Clinical anti-tumor activity in patients with various types of CTCL was observed after treatment with ARGX-110, indicating ARGX-110 as a safe and promising treatment option for advanced CTCL.DisclosuresBagot: Kyowa Kirin: Membership on an entity's Board of Directors or advisory committees; Actelion: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Innate Pharma: Consultancy, Equity Ownership, Membership...
Source: Blood - November 21, 2018 Category: Hematology Authors: Bagot, M., Maerevoet, M., Zinzani, P. L., Offner, F., Morschhauser, F., Michot, J.-M., Ribrag, V., Battistella, M., Moins, H., Calleri, A., Dalle, S., Beylot-Barry, M., Zwaenepoel, K., De Winnie, K., Marie-Cardine, A., Cayuela, J.-M., Tabanelli, V., Motta Tags: 624. Hodgkin Lymphoma and T/NK Cell Lymphoma-Clinical Studies: Poster I Source Type: research

The Odyssee Study: Prevention of Dysbiosis Complications with Autologous Fecal Microbiota Transfer (FMT) in Acute Myeloid Leukemia (AML) Patients Undergoing Intensive Treatment: Results of a Prospective Multicenter Trial
Introduction. AML standard intensive induction chemotherapy ("3+7" or equivalent) combined with wide spectrum antibiotics can dramatically alter the composition of the gut microbiota, leading to dysbiosis which is characterized by loss of microbial diversity. Such dysbiosis status can promote a pathological condition involving uncontrolled local immune responses, systemic inflammation and increased incidence of adverse events. The development of FMT-based drugs to restore microbial communities could offer novel therapeutic possibilities to reduce such adverse events and potentially improve outcomes in AML. We the...
Source: Blood - November 21, 2018 Category: Hematology Authors: Mohty, M., Malard, F., Vekhoff, A., Lapusan, S., Isnard, F., D'Incan, E., Rey, J., Saillard, C., Thomas, X., Ducastelle-Lepretre, S., Paubelle, E., Larcher, M. V., Rocher, C., Recher, C., Tavitian, S., Huguet, F., Michallet, A.-S., Gilis, L., Peterlin, P. Tags: 616. Acute Myeloid Leukemia: Novel Therapy, excluding Transplantation: Poster I Source Type: research