Sequential Combination of Low-Intensity Chemotherapy (Mini-hyper-CVD) Plus Inotuzumab Ozogamicin with or without Blinatumomab in Patients with Relapsed/Refractory Philadelphia Chromosome-Negative Acute Lymphoblastic Leukemia (ALL): A Phase 2 Trial
Conclusion: The combination of inotuzumab ozogamicin plus/minus blinatumomab with low-intensity mini-hyper-CVD chemotherapy is effective and shows encouraging results in patients with relapsed/refractory ALL. The risk of VOD can be minimized with fractionated inotuzumab ozogamicin dosing.DisclosuresSasaki: Otsuka Pharmaceutical: Honoraria. Ravandi: Xencor: Research Funding; Amgen: Honoraria, Research Funding, Speakers Bureau; Jazz: Honoraria; Seattle Genetics: Research Funding; Seattle Genetics: Research Funding; Abbvie: Research Funding; Sunesis: Honoraria; Astellas Pharmaceuticals: Consultancy, Honoraria; Sunesis: Honora...
Source: Blood - November 21, 2018 Category: Hematology Authors: Sasaki, K., Kantarjian, H. M., Ravandi, F., Short, N. J., Kebriaei, P., Huang, X., Rytting, M. E., Jain, N., Konopleva, M. Y., Garcia-Manero, G., Champlin, R. E., Kadia, T. M., Cortes, J. E., Estrov, Z. E., Takahashi, K., Mace, M., Khouri, M., Nasnas, P., Tags: 614. Acute Lymphoblastic Leukemia: Therapy, excluding Transplantation: Targeted Therapy in ALL: Immunotherapy and Beyond Source Type: research

Blinatumomab for Minimal Residual Disease (MRD) in Adults with B-Cell Precursor Acute Lymphoblastic Leukemia (BCP-ALL): Median Overall Survival (OS) Is Not Reached in Complete MRD Responders at a Median Follow-up of 53.1 Months
Conclusions: In this multinational study of adults with BCP-ALL in hematologic complete remission with persistent MRD or MRD relapse at baseline, median OS was 36.5 months after blinatumomab treatment, with median long-term follow-up of 53.1 months, and OS reached a plateau. Median OS was not estimable (ie, not reached) among the patients who had achieved a complete MRD response after cycle 1 of blinatumomab treatment, or among the subsets of patients who had achieved a complete MRD response with blinatumomab either in CR1 or with subsequent HSCT in CCR. These results provide further support for the long-term benefits in O...
Source: Blood - November 21, 2018 Category: Hematology Authors: Goekbuget, N., Dombret, H., Zugmaier, G., Bonifacio, M., Graux, C., Faul, C., Topp, M. S., Bruggemann, M., Taylor, K., Bargou, R. Tags: 614. Acute Lymphoblastic Leukemia: Therapy, excluding Transplantation: Targeted Therapy in ALL: Immunotherapy and Beyond Source Type: research

Checkpoint Inhibitors Augment CD19-Directed Chimeric Antigen Receptor (CAR) T Cell Therapy in Relapsed B-Cell Acute Lymphoblastic Leukemia
We report our single institution experience of the use of PD-1 inhibitors in patients with relapsed or refractory B lymphoblastic malignancies treated with CD19-directed CAR T cell therapy.Methods: Patients treated with CD19-directed CAR T cell therapy (murine CTL019 or humanized CTL119) at the Children's Hospital of Philadelphia who demonstrated repeated early CAR T cell loss or partial/no response to CAR T cell therapy received a PD-1 inhibitor starting no sooner than 14 days after CAR T cell infusion and after resolution of cytokine release syndrome (CRS) symptoms, with the possibility of repeated doses up to every 3 we...
Source: Blood - November 21, 2018 Category: Hematology Authors: Li, A. M., Hucks, G. E., Dinofia, A. M., Seif, A. E., Teachey, D. T., Baniewicz, D., Callahan, C., Fasano, C., McBride, B., Gonzalez, V., Nazimuddin, F., Porter, D. L., Lacey, S. F., June, C. H., Grupp, S. A., Maude, S. L. Tags: 614. Acute Lymphoblastic Leukemia: Therapy, excluding Transplantation: Targeted Therapy in ALL: Immunotherapy and Beyond Source Type: research

Ivosidenib or Enasidenib Combined with Induction and Consolidation Chemotherapy in Patients with Newly Diagnosed AML with an IDH1 or IDH2 Mutation Is Safe, Effective, and Leads to MRD-Negative Complete Remissions
CONCLUSION: Ivosidenib or enasidenib in combination with induction and consolidation therapy has an acceptable safety profile with robust remission rates, MRD-negative CRs, and mutation clearance in a population of older, high-risk patients with mIDH AML. The clinical benefit of adding ivosidenib or enasidenib to induction, consolidation and maintenance therapy for patients with newly diagnosed mIDH AML will be further evaluated in a randomized phase 3 trial.DisclosuresStein: Celgene: Consultancy; Agios: Consultancy; Daiichi Sankyo: Consultancy; Bayer: Consultancy; Pfizer: Consultancy; Novartis: Consultancy. DiNardo: Karyo...
Source: Blood - November 21, 2018 Category: Hematology Authors: Stein, E. M., DiNardo, C. D., Fathi, A. T., Mims, A. S., Pratz, K. W., Savona, M. R., Stein, A. S., Stone, R. M., Winer, E. S., Seet, C. S., Dohner, H., Pollyea, D. A., McCloskey, J. K., Odenike, O., Lowenberg, B., Ossenkoppele, G. J., Patel, P. A., Rosha Tags: 616. Acute Myeloid Leukemia: Novel Therapy, excluding Transplantation: Targeted Therapy Source Type: research

Ivosidenib (AG-120) Induced Durable Remissions and Transfusion Independence in Patients with IDH1-Mutant Untreated AML: Results from a Phase 1 Dose Escalation and Expansion Study
CONCLUSION: Ivosidenib monotherapy was well tolerated in patients with untreated mIDH1 AML, and induced durable remissions and transfusion independence in a molecularly defined, poor prognosis, elderly patient population with high rates of secondary AML, and prior hypomethylating agent exposure. These results support the role of ivosidenib as an effective, oral, targeted treatment for patients with untreated mIDH1 AML who are not eligible for intensive chemotherapy.DisclosuresRoboz: Argenx: Consultancy; Orsenix: Consultancy; Jazz Pharmaceuticals: Consultancy; Cellectis: Research Funding; Sandoz: Consultancy; Aphivena Thera...
Source: Blood - November 21, 2018 Category: Hematology Authors: Roboz, G. J., DiNardo, C. D., Stein, E. M., de Botton, S., Mims, A. S., Prince, G. T., Altman, J. K., Arellano, M. L., Donnellan, W. B., Erba, H. P., Mannis, G. N., Pollyea, D. A., Stein, A. S., Uy, G. L., Watts, J. M., Fathi, A. T., Kantarjian, H. M., Ta Tags: 616. Acute Myeloid Leukemia: Novel Therapy, excluding Transplantation: Targeted Therapy Source Type: research

Efficacy and Safety of Single-Agent Quizartinib (Q), a Potent and Selective FLT3 Inhibitor (FLT3i), in Patients (pts) with FLT3-Internal Tandem Duplication (FLT3-ITD)-Mutated Relapsed/Refractory (R/R) Acute Myeloid Leukemia (AML) Enrolled in the Global, Phase 3, Randomized Controlled Quantum-R Trial
Conclusions: This report confirms the survival benefit observed with single-agent Q compared with SC in pts with R/R FLT3-ITD AML and the favorable Q safety profile, providing evidence of meaningful clinical benefit in pts who have few options. These results are paradigm changing in the R/R FLT3-ITD AML treatment setting.DisclosuresCortes: Pfizer: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Daiichi Sankyo: Consultancy, Research Funding; Astellas Pharma: Consultancy, Research Funding; Arog: Research Funding. Khaled: Juno: Other: Travel Funding; Daiichi: Consultancy; Alexion: Consultancy, Speakers...
Source: Blood - November 21, 2018 Category: Hematology Authors: Cortes, J. E., Khaled, S. K., Martinelli, G., Perl, A. E., Ganguly, S., Russell, N. H., Kramer, A., Dombret, H., Hogge, D., Jonas, B. A., Leung, A. Y.- H., Mehta, P., Montesinos, P., Radsak, M. P., Sica, S., Arunachalam, M., Holmes, M., Kobayashi, K., Nam Tags: 616. Acute Myeloid Leukemia: Novel Therapy, excluding Transplantation: Targeted Therapy Source Type: research

Updated Results from a Phase 1 Study of Gilteritinib in Combination with Induction and Consolidation Chemotherapy in Subjects with Newly Diagnosed Acute Myeloid Leukemia (AML)
Conclusions: Gilteritinib can be safely combined with intensive chemotherapy, and given as single-agent maintenance therapy in subjects with newly diagnosed AML. Treatment was well tolerated. High response rates were observed in FLT3mut+ subjects after treatment with either idarubicin or daunorubicin in combination with two different gilteritinib administration schedules.DisclosuresPratz: Millenium/Takeda: Research Funding; AbbVie: Consultancy, Research Funding; Agios: Research Funding; Astellas: Consultancy, Research Funding; Boston Scientific: Consultancy. Altman: Astellas Pharma: Other; Agios: Other: Payment to the inst...
Source: Blood - November 21, 2018 Category: Hematology Authors: Pratz, K. W., Cherry, M., Altman, J. K., Cooper, B., Cruz, J. C., Jurcic, J. G., Levis, M. J., Lin, T. L., Perl, A. E., Podoltsev, N. A., Schiller, G. J., Liu, C., Bahceci, E. Tags: 616. Acute Myeloid Leukemia: Novel Therapy, excluding Transplantation: Targeted Therapy Source Type: research

Patterns of Care of Diffuse Large B Cell Lymphoma Patients 80 Years and Older: Worse Outcomes after Treatment without Increased Relapse
Introduction: Very advanced age (≥80 years) DLBCL patients have worse prognosis. These unfavorable outcomes are largely considered to be a result of the combined effects of increased comorbidities, frailty, diminished tolerance and access to effective chemoimmunotherapy. It is not clear yet whether DLBCL patients of very advanced age have disease that is intrinsically more aggressive.Methods: We accessed the Stem Cell Transplant and Hematologic Malignancies database of University Hospitals Seidman Cancer Center for DLBCL patients diagnosed between 2000 and 2016. Information collected included demographic characteristics...
Source: Blood - November 21, 2018 Category: Hematology Authors: Keenan, M., Boughan, K. M., Cooper, B., Gallogly, M. M., Gerson, S. L., Lazarus, H. M., Malek, E., Metheny, L., Otegbeye, F., Tomlinson, B. K., Moore, E., Oduro, K. A., Beck, R., Meyerson, H., de Lima, M., Caimi, P. F. Tags: 627. Aggressive Lymphoma (Diffuse Large B-Cell and Other Aggressive B-Cell Non-Hodgkin Lymphomas)-Results from Retrospective/Observational Studies: Outcomes Of Lymphoma In The Elderly Source Type: research

Results of the Myeloproliferative Neoplasms - Research Consortium (MPN-RC) 112 Randomized Trial of Pegylated Interferon Alfa-2a (PEG) Versus Hydroxyurea (HU) Therapy for the Treatment of High Risk Polycythemia Vera (PV) and High Risk Essential Thrombocythemia (ET)
ConclusionThe final analysis of MPN-RC 112 revealed that the CR rates in pts with high risk ET/PV treated with PEG and HU at 12 and 24 months were similar. PEG was associated with a higher rate of grade 3/4 toxicity. Each drug appeared equally capable of modifying the natural history of high risk ET/PV based upon their effects on spleen size, karyotypic abnormalities, histopathological parameters and the low incidence of thrombotic complications and disease evolution in both arms.DisclosuresMascarenhas: Novartis: Research Funding; Promedior: Research Funding; Celgene: Membership on an entity's Board of Directors or advisor...
Source: Blood - November 21, 2018 Category: Hematology Authors: Mascarenhas, J., Kosiorek, H. E., Prchal, J. T., Rambaldi, A., Berenzon, D., Yacoub, A., Harrison, C. N., McMullin, M. F., Vannucchi, A. M., Ewing, J., O'Connell, C. L., Kiladjian, J.-J., Mead, A. J., Winton, E. F., Leibowitz, D. S., De Stefano, V., Arcas Tags: 634. Myeloproliferative Syndromes: Clinical: Interferon Therapy and Mutational Analysis in the MPNs Source Type: research

Anti-CD20 Monoclonal Antibodies Hijack the B-Cell Receptor Signaling Cascade Thereby Activating the NOTCH1 Signaling Pathway
NOTCH1 is a cell surface receptor, regulation of which depends on the integrity and subsequent cleavage of its inhibitory domain. Subtle mechanical forces transmitted after ligand-binding [Wang et al., 2013] or removal of Ca2+-ions [Rand et al., 2000] make the site accessible for cleavage, resulting in release of the transcription factor NICD1. Mutations in NOTCH1 that prolong NICD1 activity have been found in chronic lymphocytic leukemia (CLL) with enrichment in up to 30% of Richter transformation (RT). Clinical trials have revealed that NOTCH1 mutant CLL derives no benefit from the addition of type I anti-CD20 monoclonal...
Source: Blood - November 21, 2018 Category: Hematology Authors: Edelmann, J., Britton, D. J., Vilventhraraja, E., Dokal, A., Holzmann, K., Cragg, M. C., Braun, A., Cutillas, P., Gribben, J. G. Tags: 641. CLL: Biology and Pathophysiology, excluding Therapy: Mechanisms of Action and Resistance to Targeted Agents Source Type: research

HDP101, a Novel B-Cell Maturation Antigen (BCMA)-Targeted Antibody Conjugated to {alpha}-Amanitin, Is Active Against Myeloma with Preferential Efficacy Against Pre-Clinical Models of Deletion 17p
Background:Deletion (del) of 17p involving the p53 tumor suppressor (TP53) remains an adverse prognostic factor in multiple myeloma (MM) despite the use of novel agents as well as high-dose chemotherapy with autologous stem cell rescue. Genomic TP53 deletion can cause haploinsufficiency of nearby genes, such as RNA polymerase II subunit A (POLR2A), which ia also located on 17p13.1. We therefore hypothesized that del 17p could reduce POLR2A expression and enhance sensitivity to a-Amanitin, a potent and specific inhibitor of POLR2A and RNA polymerase III.Methods:Pre-clinical studies were performed using HDP101, a monoclonal ...
Source: Blood - November 21, 2018 Category: Hematology Authors: Singh, R. K., Jones, R. J., Hong, S., Shirazi, F., Wang, H., Kuiatse, I., Pahl, A., Orlowski, R. Z. Tags: 652. Myeloma: Pathophysiology and Pre-Clinical Studies, excluding Therapy: Development of Novel Immunotherapeutic Approaches in Multiple Myeloma Source Type: research

Results of the Pivotal STORM Study (Part 2) in Penta-Refractory Multiple Myeloma (MM): Deep and Durable Responses with Oral Selinexor Plus Low Dose Dexamethasone in Patients with Penta-Refractory MM
Introduction: Selinexor is a novel, oral Selective Inhibitor of Nuclear Export (SINE) compound that blocks exportin 1 (XPO1). Selinexor treatment results in nuclear accumulation and activation of tumor suppressor proteins, inhibition of NF-kB, and translational suppression of several oncoprotein mRNAs (e.g., c-myc, cyclin D).Multiple myeloma (MM) remains incurable, and most patients (pts) eventually progress through standard drug classes of proteasome inhibitors (PIs), immunomodulatory drugs (IMiDs), anti-CD38 mAbs and others. The increased use of combinations in MM treatment, (PIs/IMiDs/mAbs), has led to a growing number ...
Source: Blood - November 21, 2018 Category: Hematology Authors: Chari, A., Vogl, D. T., Dimopoulos, M. A., Nooka, A. K., Huff, C. A., Moreau, P., Cole, C. E., Richter, J., Dingli, D., Vij, R., Tuchman, S. A., Raab, M. S., Weisel, K., Delforge, M., Kaminetzky, D., Cornell, R. F., Stewart, A. K., Hoffman, J., Godby, K. Tags: 653. Myeloma: Therapy, excluding Transplantation: Antibodies and Targeted Therapies Source Type: research

Children and Adults with Steroid-Refractory Acute Graft-Versus-Host Disease Respond to Treatment with the Mesenchymal Stroma Cell Preparation "MSC-FFM": Treatment Results for 92 Consecutive Patients
Conclusion: MSC-FFM emanates as a highly efficacious treatment for severe pediatric and adult advanced GvHD, with OR in excess of 80% and survival rates approximating those of patients without GvHD. The very low relapse mortality may suggest that severe GvHD effectively suppresses leukemic recurrence. Better and faster responses of SR- vs. MR-GvHD make a case for early treatment with MSC-FFM.DisclosuresBader: Medac: Patents & Royalties, Research Funding; Cellgene: Consultancy; Neovii: Research Funding; Riemser: Research Funding; Novartis: Consultancy, Speakers Bureau. Kuci: Medac: Patents & Royalties. Kuci: Medac: ...
Source: Blood - November 21, 2018 Category: Hematology Authors: Bader, P., Kuci, S., Kuci, Z., Bakhtiar, S., Basu, O., Bug, G., Dennis, M., Greil, J., Barta, A., Kallay, K., Lang, P., Lucchini, G., Pol, R., Schulz, A., Sykora, K.-W., Teichert von Luettichau, I., Herter-Sprie, G., Uddin, M. A., Jenkin, P., Alsultan, A. Tags: 722. Clinical Allogeneic Transplantation: Acute and Chronic GVHD, Immune Reconstitution: GVHD Treatment and Prevention Strategies Source Type: research

Results of a Prospective, Multicenter, Phase I/II Clinical Study in Pediatric and Adult Patients Using TCR Alpha/Beta and CD19 Depleted Haploidentical Hematopoietic Stem Cell Grafts Following Reduced-Intensity Conditioning
Conclusion:The transplantation of TCRαβ and CD19 depleted haploidentical hematopoietic stem cell grafts was safe and feasible. Decentralized production using the CliniMACS System was feasible and reliably resulted in grafts containing sufficient numbers of stem cells with only minimal numbers of co-infused TCRαβ T cells. None of the patients developed grade III-IV aGVHD and incidence of cGVHD was acceptable. Given the heterogeneous patient cohort with respect to age, disease, remission status and number of previous transplants, the outcome of patients after 2 years follow-up is promising.DisclosuresLa...
Source: Blood - November 21, 2018 Category: Hematology Authors: Lang, P., Handgretinger, R., Meisel, R., Mielke, S., Niederwieser, D., Schlegel, P. G., Greil, J., Schulz, A., Bader, P., Brecht, A., Bunjes, D., Kuball, J., Schumm, M., Eyrich, M. K., Vucinic, V., Wiesneth, M., Bonig, H., Westinga, K., Karitzky, S., Holt Tags: 722. Clinical Allogeneic Transplantation: Acute and Chronic GVHD, Immune Reconstitution: GVHD Treatment and Prevention Strategies Source Type: research

A Phase 1b Study of Intravenous Vedolizumab Plus Standard of Care for Graft-Versus-Host Disease Prophylaxis in Subjects Undergoing Allogeneic Hematopoietic Stem Cell Transplantation for Hematologic Malignancies: 6-Month Results
ConclusionsIn subjects receiving vedolizumab in addition to standard GvHD prophylaxis, there were no DLTs or engraftment failures at 6 months after HCT, and the TEAEs observed have been as expected in this population. The low cumulative incidences of grade II-IV and grade III-IV aGvHD are promising; there were no cases of lower GI aGvHD greater than stage 1. Intravenous vedolizumab 300 mg added to standard GvHD prophylaxis for the prevention of GI aGvHD merits further study.DisclosuresChen: Takeda Pharmaceuticals: Consultancy; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees; Magenta...
Source: Blood - November 21, 2018 Category: Hematology Authors: Chen, Y.-B., Shah, N. N., Renteria, A. S., Cutler, C. S., Jansson, J., Akbari, M., Chen, C., Quadri, S., Parfionovas, A., Devine, S. Tags: 722. Clinical Allogeneic Transplantation: Acute and Chronic GVHD, Immune Reconstitution: GVHD Treatment and Prevention Strategies Source Type: research

Low-Dose Interleukin-2 Therapy Enhances Cytotoxicity of CD56bright NK Cells in Patients with Chronic Gvhd
Conclusion: Single cell mass cytometry revealed that daily low dose IL-2 therapy induces selective expansion, activation and increased expression of activating NK receptors in CD56bright NK cells. CD56dim NK cells were not affected by IL-2 therapy. In vitro assays revealed that cytolytic activity of CD56bright NK cells increased during IL-2 treatment and exceeded the cytotoxicity of CD56dim NK cells. CD56bright NK cells, traditionally considered to be minimally tumor-responsive, are effectively stimulated by daily low dose IL-2 exposure to enable potent cytotoxicity in response to tumor targets. In patients receiving low-d...
Source: Blood - November 21, 2018 Category: Hematology Authors: Kubo, T., Romee, R., Koreth, J., Belizaire, R., Kamihara, Y., Liu, H., Asano, T., Whangbo, J., Hirakawa, M., Nikiforow, S., Gooptu, M., Ho, V. T., Cutler, C. S., Alyea, E. P., Antin, J. H., Soiffer, R. J., Ritz, J. Tags: 722. Clinical Allogeneic Transplantation: Acute and Chronic GVHD, Immune Reconstitution: GVHD Treatment and Prevention Strategies Source Type: research

Clinical Impact of Clonal Hematopoiesis after Autologous Stem Cell Transplantation for Lymphoma: A National Population-Based Cohort Study
Background:Somatic driver mutations in hematopoietic cells may lead to clonal hematopoiesis of indeterminate potential (CHIP). In patients with lymphoma CHIP has been associated with increased risk of therapy-related myeloid neoplasms (tMN) and inferior survival after autologous stem cell transplantation as demonstrated in a large single center study and in a case-control study (Gibson CJ et al., JCO 2017 and Berger G et al., Blood 2018). Here, we investigated the clinical impact of clonal hematopoiesis in a nation-wide population-based cohort of Danish lymphoma patients undergoing autologous transplant with prospective da...
Source: Blood - November 21, 2018 Category: Hematology Authors: Husby, S., Francesco, F., Nielsen, C., Sorensen, B., Baech, J., Hansen, J. W., Gonzalez, G. G. R., Arboe, B., Andersen, L. P., Hastrup, E. K., Fischer-Nielsen, A., Saekmose, S. G., Hansen, P. B., Christiansen, I., Clasen-Linde, E., Knudsen, L. M., Grell, Tags: 731. Clinical Autologous Transplantation: Results: Autologous Transplantation: Clonal Hematopoiesis, Microbiota, AML, NHL, and Autoimmune Diseases Source Type: research

FLT3 and NPM1 Are Powerful Determinants of Outcome in Acute Myeloid Leukemia Patients Treated with Autologous Stem Cell Transplantation: An Analysis By the Acute Leukemia Working Party of the EBMT
Background: While intensive consolidation therapy with autologous stem cell transplantation (ASCT) can secure a remission in selected Acute Myeloid Leukemia (AML) patients with intermediate-risk cytogenetics, a substantial proportion will ultimately relapse. Knowledge of the mutational status of FMS like tyrosine kinase 3 internal tandem duplication (FLT3-ITD) and nucleophosmin (NPM) 1 and their possible combinations could further refine a subset of intermediate cytogenetic risk patients who may benefit from ASCT. However, data are limited. We, therefore, set out to evaluate the impact of FLT3-ITD and NPM1 in a large cohor...
Source: Blood - November 21, 2018 Category: Hematology Authors: Shouval, R., Labopin, M., Bomze, D., Baerlocher, G. M., Foa, R., Blaise, D., Haenel, M., Forcade, E., Huynh, A., Saccardi, R., Milone, G., Zuckerman, T., Remenyi, P., Esteve, J., Gorin, N. C., Mohty, M., Nagler, A. Tags: 731. Clinical Autologous Transplantation: Results: Autologous Transplantation: Clonal Hematopoiesis, Microbiota, AML, NHL, and Autoimmune Diseases Source Type: research

Phase I Study of Yttrium-90 Labeled ANTI-CD25 (aTac) Monoclonal Antibody PLUS BEAM for Autologous Hematopoietic CELL Transplantation (AHCT) in Patients with Mature T-CELL NON-Hodgkin Lymphoma, the "a-TAC-BEAM Regimen"
Conclusion: aTac- BEAM appears to be safe as an ASCT conditioning regimen for PTCL with no increased toxicity as compared to the historical toxicities seen with BEAM alone in this patient population (D'Amore 2012 J of Clin Onc). The dose level 0.6mCi/kg will likely be the recommended phase II dose. An expanded phase is planned to evaluate the efficacy of this regimen followed by a randomized trial of BEAM alone plus a combination of aTac- BEAM.Figure 1.DisclosuresHerrera: Seattle Genetics: Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; Immune Design: Researc...
Source: Blood - November 21, 2018 Category: Hematology Authors: Zain, J., Simpson, J., Palmer, J., Wong, J., Dandapani, S., Colcher, D., Karras, N., Herrera, A. F., Salhotra, A., Nademanee, A. P., Nakamura, R., Smith, E. P., Tsai, N.-C., Yamauchi, D., Poku, K., Biglang-awa, V., Shively, J. E. Tags: 731. Clinical Autologous Transplantation: Results: Autologous Transplantation: Clonal Hematopoiesis, Microbiota, AML, NHL, and Autoimmune Diseases Source Type: research

Resource Utilization Early after Chimeric Antigen Receptor (CAR) T Cell Infusion for Hematologic Malignancies
Conclusion: While providing potential clinical benefit, CAR T cell therapy utilizes resources across the therapeutic spectrum, and increasing use of this therapeutic modality can create challenges in institutional resource capacity. Identifying these resources will allow for better care delivery and allocation of funds. Further refinement of CAR T cell products and improvements in CAR T cell-related toxicity management may permit safer delivery of this therapy and reduce costs per patient. Additional analysis of resource utilization among patients treated with commercial CAR T cell products, as well as comparison with alte...
Source: Blood - November 21, 2018 Category: Hematology Authors: Shah, G. L., Park, J. H., Sauter, C. S., Duck, E., Halton, E., Palomba, M. L., Batlevi, C. L., Younes, A., Geyer, M. B., Smith, E. L., Mailankody, S., Mead, E., Santomasso, B., Perales, M.-A., Sabbatini, P., Giralt, S., Brentjens, R. J., Bach, P. Tags: 902. Health Services Research-Malignant Diseases: Overuse, Costs, and Utilization of Health Services Source Type: research

Association between Transplant Volumes and 30-Day Readmissions Following Allogeneic Hematopoietic Cell Transplantation (allo-HCT) in the US
Background: Readmissions within 30 days after index hospitalization is a quality and cost-containment metric. Financial penalties to hospitals with high rates of risk-adjusted readmissions have been expanded beyond medical conditions like heart failure and pneumonia. Published data show significant heterogeneity in readmission rates and recent data from elderly Medicare beneficiaries reported a 17.8% readmission rate for targeted conditions. Allo-HCT is a widely used therapeutic strategy in the management of various hematologic disorders like acute myelogenous (AML) and lymphoblastic leukemia (ALL). However, allo-HCT readm...
Source: Blood - November 21, 2018 Category: Hematology Authors: Dhakal, B., Giri, S., Levin, A., Lisa, R., Fenske, T. S., Chhabra, S., Shah, N. N., Szabo, A., D'Souza, A., Pasquini, M. C., Hari, P., Hamadani, M. Tags: 902. Health Services Research-Malignant Diseases: Overuse, Costs, and Utilization of Health Services Source Type: research

Results from a Phase 3, Multicenter, Non-Inferiority Study of Ravulizumab (ALXN1210) Versus Eculizumab in Adult Patients with Paroxysmal Nocturnal Hemoglobinuria Currently Treated with Eculizumab
IntroductionRavulizumab, an innovative complement C5 inhibitor given every 8 weeks (q8w), was recently demonstrated in a large phase 3 study of patients (pts) with paroxysmal nocturnal hemoglobinuria (PNH) and naïve to complement inhibitor therapy to be non-inferior to eculizumab given every 2 weeks (q2w) across all endpoints that measured different aspects of PNH disease (transfusion avoidance [TA], lactate dehydrogenase normalization [LDH-N], percent LDH reduction, breakthrough hemolysis [BTH], Functional Assessment of Chronic Illness Therapy [FACIT]-Fatigue, and hemoglobin stabilization [HGB-S]) (Lee JW et al. EHA ...
Source: Blood - November 21, 2018 Category: Hematology Authors: Kulasekararaj, A. G., Hill, A., Rottinghaus, S. T., Langemeijer, S., Wells, R. A., Gonzalez-Fernandez, F. A., Gaya, A., Lee, J.-W., Ojeda Gutierrez, E., Piatek, C. I., Szer, J., Risitano, A. M., Nakao, S., Bachman, E., Shafner, L., Damokosh, A. I., Ortiz, Tags: 101. Red Cells and Erythropoiesis, Structure and Function, Metabolism, and Survival, Excluding Iron: Inherited and Acquired Anemias Source Type: research

Sorafenib As Maintenance Therapy Post Allogeneic Stem Cell Transplantation for FLT3-ITD Positive AML: Results from the Randomized, Double-Blind, Placebo-Controlled Multicentre Sormain Trial
Conclusion: Sorafenib maintenance therapy after allo-SCT is feasible and significantly reduces the risk of relapse or death in patients with FLT3-ITD positive AML. OS results will be presented at the meeting.Figure 1.DisclosuresBurchert: Bristol Myers Squibb: Honoraria, Research Funding; Bayer: Research Funding; Pfizer: Honoraria; AOP Orphan: Honoraria, Research Funding; Novartis: Research Funding. Bug: Amgen: Honoraria; Neovii: Other: Travel Grant; Novartis Pharma: Honoraria, Research Funding; Astellas Pharma: Other: Travel Grant; Jazz Pharmaceuticals: Other: Travel Grant; Celgene: Honoraria; Janssen: Other: Travel Grant....
Source: Blood - November 21, 2018 Category: Hematology Authors: Burchert, A., Bug, G., Finke, J., Stelljes, M., Rollig, C., Wasch, R., Bornhauser, M., Berg, T., Lang, F., Ehninger, G., Serve, H., Zeiser, R., Wagner, E.-M., Kroeger, N., Wolschke, C., Schleuning, M., Elmaagacli, A., Gotze, K. S., Schmid, C., Jost, E., W Tags: 613. Acute Myeloid Leukemia: Clinical Studies: Maintenance after Allogeneic Stem Cell Transplant and Management of Refractory/Relapsed AML Source Type: research

Outcomes with Subsequent FLT3-Inhibitor (FLT3i) Based Therapies in FLT3-Mutated (mu) Patients (pts) Refractory/Relapsed (R/R) to One or More Prior FLT3 Inhibitor Based Therapies: A Single Center Experience
Conclusions: ORRs dropped from 49% to 27% to 17% with first, second, and third FLT3i-based therapies. Combining FLT3is with low or high intensity chemotherapy appeared superior to single agent in all exposure groups. LIT (HMA and LDAC)-based combinations had encouraging ORRs of 46% and 29% in the second and third FLT3i exposure, likely because many pts received CCT-based combinations as initial therapy. Quizartinib and gilteritinib were effective with ORR of 35-40% even when used as a second FLT3i. This is a first attempt at identifying benchmark response rates for second and third FLT3i exposures, for developing novel FLT...
Source: Blood - November 21, 2018 Category: Hematology Authors: Alfayez, M., Kantarjian, H. M., Ravandi, F., Konopleva, M. Y., Garcia-Manero, G., Kadia, T. M., Jabbour, E. J., Borthakur, G., DiNardo, C. D., Estrov, Z. E., Pemmaraju, N., Pierce, S. A., Yilmaz, M. E., Short, N. J., Takahashi, K., Assi, R., Andreeff, M., Tags: 613. Acute Myeloid Leukemia: Clinical Studies: Maintenance after Allogeneic Stem Cell Transplant and Management of Refractory/Relapsed AML Source Type: research

Outcomes of Relapsed/Refractory Patients with IDH1/2 Mutated AML Treated with Non-Targeted Therapy: Results from the NCRI AML Trials
Introduction: The increasing delineation of acute myeloid leukemia (AML) has identified a number of genetic mutations which may be amenable to targeted therapies. However, such mutations typically only occur in a minority of patients, and this relative paucity presents challenges in drug development. Even for more common mutations such as FLT3 ITD, randomised trials can take many years to complete, and there is the issue of how to deal with patients who are tested but not eligible. Earlier phase trials therefore tend to be single arm studies, and often recruit in the relapsed/refractory population, where eligibility is kno...
Source: Blood - November 21, 2018 Category: Hematology Authors: Hills, R. K., Gale, R., Linch, D. C., Huntly, B. J. P., Papaemmanuil, E., Vyas, P., Burnett, A. K., Russell, N. H. Tags: 613. Acute Myeloid Leukemia: Clinical Studies: Maintenance after Allogeneic Stem Cell Transplant and Management of Refractory/Relapsed AML Source Type: research

Clinical Responses to CAR.CD30-T Cells in Patients with CD30+ Lymphomas Relapsed after Multiple Treatments Including Brentuximab Vedotin
We present here the results of a phase 1b/2 trial of CD30.CAR-Ts administered after lymphodepleting chemotherapy in pts with r/r CD30+ Hodgkin (HL) and Non-Hodgkin lymphoma (NHL).Methods:The primary objective of the phase 1b portion of the study was to determine the recommended phase 2 dose level (RP2DL) of CD30.CAR-Ts using a standard 3+3 design. Two dose levels were tested: 1 x 108 CAR-Ts/m2 (DL1) and 2 x 108 CAR-Ts/m2 (DL2). For lymphodepletion, the first 8 pts (including the first 3 pts treated at DL1) received 2 days of bendamustine (benda) 90 mg/m2, while the 10 remaining pts received 3 days of benda 70 mg/m2 and flu...
Source: Blood - November 21, 2018 Category: Hematology Authors: Grover, N. S., Park, S. I., Ivanova, A., Eldridge, P., McKay, K., Cheng, C. J. A., Laing, S., Covington, D., West, J., Sharf, S. E., Morrison, J. K., Scott, S., Crecelius, E., Shelley, D., Alexander, M., Buchanan, F. B., Kassam, E. H., McElfresh, M., Pint Tags: 624. Hodgkin Lymphoma and T/NK Cell Lymphoma-Clinical Studies: Immunotherapy and Targeted Strategies Source Type: research

The Combination of Duvelisib, a PI3K-{delta},{gamma} Inhibitor, and Romidepsin Is Highly Active in Relapsed/Refractory Peripheral T-Cell Lymphoma with Low Rates of Transaminitis: Results of Parallel Multicenter, Phase 1 Combination Studies with Expansion Cohorts
Conclusion: Duvelisib in combination with romidepsin is highly active in pts with PTCL with tolerable side effects. Duvelisib can be safely combined with romidepsin at a 3-fold higher dose than with bortezomib (75 mg BID vs 25 mg BID) with much lower rate of Gr 3-4 transaminitis than single-agent duvelisib at the same dose. The high response rates and safety of Arm A (Duvelisib + Romidepsin) in PTCL appears to be a potential therapeutic advance and warrants further evaluation in a larger study.DisclosuresHorwitz: Portola: Consultancy; Innate Pharma: Consultancy; Forty Seven: Consultancy, Research Funding; Kyowa-Hakka-Kirin...
Source: Blood - November 21, 2018 Category: Hematology Authors: Horwitz, S. M., Moskowitz, A. J., Jacobsen, E. D., Mehta-Shah, N., Khodadoust, M. S., Fisher, D. C., Myskowski, P., Wang, E. B. K., Tawa, M., Davey, T., Blouin, W., Hancock, H., Ganesan, N., Galasso, N., Marzouk, E., Bahgat, A., Jester, H., Fong, S., Butt Tags: 624. Hodgkin Lymphoma and T/NK Cell Lymphoma-Clinical Studies: Immunotherapy and Targeted Strategies Source Type: research

IPH4102; An Anti-KIR3DL2 Monoclonal Antibody in Refractory Sezary Syndrome: Results from a Multicenter Phase 1 Trial
Conclusions: IPH4102 is highly effective in patients with refractory SS. It induces meaningful clinical activity and improves quality of life placing it as an encouraging treatment option for these patients. Further development in SS and other T-cell malignancies is underway.DisclosuresBagot: Actelion: Membership on an entity's Board of Directors or advisory committees; Innate Pharma: Consultancy, Equity Ownership, Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Kyowa Kirin: Membership on an entity's Board of Directors or advi...
Source: Blood - November 21, 2018 Category: Hematology Authors: Bagot, M., Porcu, P., William, B. M., Battistella, M., Vermeer, M., Whittaker, S., Ram-Wolff, C., Khodadoust, M. S., Sicard, H., Azim, H. A., Kim, Y. H. Tags: 624. Hodgkin Lymphoma and T/NK Cell Lymphoma-Clinical Studies: Immunotherapy and Targeted Strategies Source Type: research

Imetelstat Is Effective Treatment for Patients with Intermediate-2 or High-Risk Myelofibrosis Who Have Relapsed on or Are Refractory to Janus Kinase Inhibitor Therapy: Results of a Phase 2 Randomized Study of Two Dose Levels
Conclusions: Imetelstat at 9.4 mg/kg IV every 3 weeks has demonstrated clinical activity in int-2 or high-risk MF patients who are relapsed/refractory to JAKi, notably in observed OS. Though no formal study has reported survival for patients who are truly relapsed/refractory to JAKi, median OS of patients who were previously treated with JAKi has been reported to be 12-14 mo (Kuykendall Ann Hematol 2018; Newberry Blood 2017). The safety profile for imetelstat was considered acceptable for this poor-prognosis population. Imetelstat at 9.4 mg/kg IV every 3 weeks is a promising agent for JAKi-pretreated MF patients and warran...
Source: Blood - November 21, 2018 Category: Hematology Authors: Mascarenhas, J., Komrokji, R. S., Cavo, M., Martino, B., Niederwieser, D., Reiter, A., Scott, B. L., Baer, M. R., Hoffman, R., Odenike, O., Bussolari, J., Zhu, E., Huang, F., Rose, E., Sherman, L., Dougherty, S., Feller, F. M., Kiladjian, J.-J. Tags: 634. Myeloproliferative Syndromes: Clinical: Emerging Therapies and Prognostic Scoring in Myelofibrosis and Other MPNs Source Type: research

PRM-151 in Myelofibrosis: Efficacy and Safety in an Open Label Extension Study
Introduction: PRM-151, a recombinant human pentraxin-2 molecule, has been shown to prevent and reverse fibrosis in animal models of myelofibrosis (MF) by postulated targeting differentiation of fibrocytes (essential cells in fibrotic process) from monocytes. In the first stage of a two-stage trial, 27 patients (pts) with primary myelofibrosis (PMF), post-essential thrombocythemia/polycythemia vera (post-ET/PV) MF, and Grade 2 or 3 bone marrow fibrosis (BMF) received PRM-151 10 mg/kg IV ± ruxolitinib (RUX) for 6 cycles (24 weeks). A reduction in BMF, decrease in symptoms (MPN-SAF Total Symptom Score [TSS]), and a red...
Source: Blood - November 21, 2018 Category: Hematology Authors: Verstovsek, S., Hasserjian, R. P., Pozdnyakova, O., Veletic, I., Mesa, R. A., Foltz, L., Mascarenhas, J., Ritchie, E. K., Palmer, J., Silver, R. T., Kremyanskaya, M., van den Blink, B., Gupta, R., Manshouri, T., Yin, C. C., Estrov, Z. E., Gotlib, J. R. Tags: 634. Myeloproliferative Syndromes: Clinical: Emerging Therapies and Prognostic Scoring in Myelofibrosis and Other MPNs Source Type: research

Alisertib (MLN8237), an Oral Selective Inhibitor of Aurora Kinase a, Has Clinical Activity and Restores GATA1 Expression in Patients with Myelofibrosis
Conclusions: Alisertib is safe and well tolerated in patients with myelofibrosis with prolonged administration up to 1.7 years. In addition to providing clinical benefit, alisertib restored normal morphology and GATA1 expression in atypical megakaryocytes and reduced marrow fibrosis and mutant allele burdens. These findings demonstrate that AURKA inhibition should be further explored as a therapeutic option in myelofibrosis.Figure 1.DisclosuresSwords: AbbVie: Employment. Watts: Jazz Pharma: Consultancy, Speakers Bureau; Takeda: Research Funding. Frankfurt: Celgene, Jazz, Agios: Membership on an entity's Board of Directors ...
Source: Blood - November 21, 2018 Category: Hematology Authors: Gangat, N., Stein, B. L., Marinaccio, C., Swords, R., Watts, J. M., Gurbuxani, S., Frankfurt, O., Altman, J. K., Wen, J. Q., Farnoud, N., Famulare, C., Patel, A., Tapia, R., Handlogten, A., Dinh, Y. T., Englund, K., Patel, S., Nobrega, J. C., Tejera, D., Tags: 634. Myeloproliferative Syndromes: Clinical: Emerging Therapies and Prognostic Scoring in Myelofibrosis and Other MPNs Source Type: research

Ibrutinib + Obinutuzumab Versus Chlorambucil + Obinutuzumab As First-Line Treatment in Patients with Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma (CLL/SLL): Results from Phase 3 iLLUMINATE
Background: Ibrutinib (ibr), a first-in-class, once-daily inhibitor of Bruton's tyrosine kinase, is approved in the US and EU for patients (pts) with CLL and allows for treatment without chemotherapy. Standard of care for first-line CLL in older pts or those with comorbidities includes single-agent ibr and chemoimmunotherapy (CIT) with chlorambucil (clb) plus anti-CD20 therapy. As the addition of obinutuzumab (G) to clb provides superior efficacy over clb alone or rituximab-G, we investigated the potential for improved efficacy with addition of G to single-agent ibr vs clb-G in an international, open-label, randomized phas...
Source: Blood - November 21, 2018 Category: Hematology Authors: Moreno, C., Greil, R., Demirkan, F., Tedeschi, A., Anz, B., Larratt, L., Simkovic, M., Samoilova, O., Novak, J., Ben-Yehuda, D., Strugov, V., Gill, D., Gribben, J. G., Hsu, E., Zhou, C., Clow, F., James, D. F., Styles, L., Flinn, I. W. Tags: 642. CLL: Therapy, excluding Transplantation: Advances in Frontline Therapy of CLL Source Type: research

Acalabrutinib in Treatment-Naive (TN) Chronic Lymphocytic Leukemia (CLL): Updated Results from the Phase 1/2 ACE-CL-001 Study
Conclusion: Acalabrutinib monotherapy produced high response rates and demonstrated an acceptable safety profile in patients with TN CLL.DisclosuresFurman: Gilead: Consultancy; Loxo Oncology: Consultancy; Acerta: Consultancy, Research Funding; Genentech: Consultancy; Pharmacyclics LLC, an AbbVie Company: Consultancy; Sunesis: Consultancy; TG Therapeutics: Consultancy; Verastem: Consultancy; Incyte: Consultancy, Other: DSMB; Janssen: Consultancy; AbbVie: Consultancy. Martin: Gilead: Consultancy; Janssen: Consultancy; Bayer: Consultancy; Seattle Genetics: Consultancy; AstraZeneca: Consultancy; Kite: Consultancy. O'Brien: Jan...
Source: Blood - November 21, 2018 Category: Hematology Authors: Byrd, J. C., Woyach, J. A., Furman, R. R., Martin, P., O'Brien, S. M., Brown, J. R., Stephens, D. M., Barrientos, J. C., Devereux, S., Hillmen, P., Pagel, J. M., Chen, D.-Y., Hamdy, A., Izumi, R., Patel, P., Wang, M. H., Jain, N., Wierda, W. G. Tags: 642. CLL: Therapy, excluding Transplantation: Advances in Frontline Therapy of CLL Source Type: research

Ibrutinib, Fludarabine, Cyclophosphamide, and Obinutuzumab (iFCG) for Firstline Treatment of Patients with CLL with Mutated IGHV and without TP53 Aberrations
Conclusions: iFCG achieves high rate of U-MRD in previously-untreated patients with CLL with IGHV-M CLL. No patient has progressed and all patients who have stopped ibrutinib maintain U-MRD status.DisclosuresJain: Verastem: Research Funding; BMS: Research Funding; Abbvie: Research Funding; Astra Zeneca: Research Funding; Pfizer: Research Funding; Novimmune: Honoraria, Membership on an entity's Board of Directors or advisory committees; Servier: Research Funding; Pharmacyclics: Research Funding; Pharmacyclics: Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene:...
Source: Blood - November 21, 2018 Category: Hematology Authors: Jain, N., Thompson, P. A., Burger, J. A., Ferrajoli, A., Borthakur, G., Bose, P., Estrov, Z. E., Kadia, T. M., Takahashi, K., Garg, N., Wang, X., Kanagal-Shamanna, R., Patel, K., Lopez, W., Ayala, A., Plunkett, W., Gandhi, V., Kantarjian, H. M., O'Brien, Tags: 642. CLL: Therapy, excluding Transplantation: Advances in Frontline Therapy of CLL Source Type: research

Long-Term Remission of CLL Sustained By Pauciclonal Anti-CD19 Chimeric Antigen Receptor T (CTL019) Cell Clones
We recently demonstrated that sustained remission in 41 CLL patients treated with the CD19-specific, 4-1BB/CD3zeta-signaling chimeric antigen receptor (CAR19) T-cells correlated strongly with the expansion and persistence of the engineered T cells and that important pathways such as T cell exhaustion, glycolysis and T cell differentiation segregated responders from non-responders (Fraietta et al., 2018, Nature Medicine). We here report two advanced, chemotherapy-resistant CLL patients with the longest (7 years) follow-up on any trial of CART19 cells. Both patients had received five therapies before being treated at the Uni...
Source: Blood - November 21, 2018 Category: Hematology Authors: Melenhorst, J. J., Porter, D. L., Tian, L., Lacey, S. F., Nobles, C. L., Fraietta, J. A., Frey, N. V., Kulikovskaya, I., Gupta, M., Young, R. M., Ambrose, D. E., Siegel, D. L., Bushman, F. D., June, C. H. Tags: 703. Adoptive Immunotherapy: In Vitro, Correlative, and Early Phase Studies to Improve Safety and Efficacy of CAR-T Cells Source Type: research

A Phase I/Ib Study of Nivolumab for Relapsed Hematologic Malignancies after Allogeneic Hematopoietic Cell Transplantation (alloHCT)
CONCLUSIONS: In this first prospective clinical trial of an anti-PD1 antibody for relapsed HM post-alloHCT, severe GVHD and irAEs occurred, even at the lower dose of nivo 0.5 mg/kg, leading to early closure due to toxicity. Modest anti-tumor activity was observed mainly in lymphoid malignancies known already to be responsive to anti-PD1 therapy, which may justify further exploration of anti-PD1 therapy in those populations in trials with strategies to mitigate toxicity; however, given the more favorable safety and efficacy profile of anti-CTLA-4 therapy in other HM, our future studies focus on combining ipilimumab with nov...
Source: Blood - November 21, 2018 Category: Hematology Authors: Davids, M. S., Kim, H. T., Costello, C. L., Herrera, A. F., Locke, F. L., Maegawa, R. O., Savell, A., Mazzeo, M., Avigan, D. E., Chen, Y.-B., Nikiforow, S., Ho, V. T., Cutler, C. S., Alyea, E. P., Bachireddy, P., Wu, C. J., Streicher, H., Ball, E. D., Bas Tags: 723. Clinical Allogeneic and Autologous Transplantation: Late Complications and Approaches to Disease Recurrence: Therapy of Post-Transplantation Relapse Source Type: research

PD-1 Blockade for Diffuse Large B-Cell Lymphoma after Autologous Stem Cell Transplantation
Conclusions: Pembrolizumab administered after ASCT in patients with R/R DLBCL is feasible with toxicity similar to its use in the R/R setting for other hematological malignancies. The high rate of neutropenia on this study, which is not a common AE of pembro in other settings, may be related to the burden of prior therapy or possibly to an accentuated toxicity of pembro in this specific patient population. The 18-month progression-free rate did not meet the protocol-specified primary objective, and therefore does not support a larger confirmatory study. Future studies in this setting should likely focus on specific subsets...
Source: Blood - November 21, 2018 Category: Hematology Authors: Chen, Y.-B., Armand, P., Redd, R. A., Bsat, J., Merryman, R. W., Coleman, K., Herrera, A. F., Dahi, P. B., Nieto, Y., LaCasce, A. S., Fisher, D. C., Ng, S. Y., Odejide, O. O., Freedman, A. S., Kim, A. I., Crombie, J. L., Jacobson, C. A., Jacobsen, E. D., Tags: 723. Clinical Allogeneic and Autologous Transplantation: Late Complications and Approaches to Disease Recurrence: Therapy of Post-Transplantation Relapse Source Type: research

Post-Transplant Sorafenib Improves Overall Survival in FLT3 Mutated AML: A Report from the EBMT Acute Leukemia Working Party
Rationale: FLT3 in mutated in 30% of AML and is associated with poor prognosis. Allogeneic hematopoietic cell transplantation (allo-HCT) in first complete remission (CR) is recommended in FLT-3 ITD AML. However frequent and early post-transplant relapse leads to poor outcome. Several small studies suggested the efficacy of sorafenib as prophylactic or preemptive therapy or as treatment for relapse post allo-HCT. The purpose of this study was to assess the impact of sorafenib on outcomes of FLT3 mutated AML post allo-HCT.Patients and Methods: We identified 462 adult patients (51% males) with FLT3 mutated AML (FLT3 ITD-95%) ...
Source: Blood - November 21, 2018 Category: Hematology Authors: Bazarbachi, A., Labopin, M., Battipaglia, G., Djabali, A., Forcade, E., Arcese, W., Socie, G., Blaise, D., Passweg, J. R., Cornelissen, J. J., Chevallier, P., Maertens, J., Schaap, N., Hashaishi, K., Elcheikh, J., Malard, F., Esteve, J., Nagler, A., Mohty Tags: 723. Clinical Allogeneic and Autologous Transplantation: Late Complications and Approaches to Disease Recurrence: Therapy of Post-Transplantation Relapse Source Type: research

Phase 1/2 Study of Brentuximab Vedotin in Combination with Nivolumab in Patients with Relapsed or Refractory Classic Hodgkin Lymphoma: Part 3 (Concurrent Dosing) Results and Updated Progression-Free Survival Results from Parts 1 and 2 (Staggered Dosing)
ConclusionA concurrent dosing schedule of BV + Nivo was well tolerated with a high CR rate of 80%. Biomarkers evaluated in Part 3 indicate immune activation in the periphery following BV + Nivo. Cumulatively, the results in Part 3, along with the durable remissions noted in Parts 1 & 2, support BV + Nivo combination as an encouraging first salvage therapy prior to ASCT in pts with R/R cHL.DisclosuresAdvani: Forty Seven: Research Funding; Infinity: Research Funding; Seattle Genetics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Participated in an advisory board, Research Fundi...
Source: Blood - November 21, 2018 Category: Hematology Authors: Advani, R. H., Moskowitz, A. J., Bartlett, N. L., Vose, J. M., Ramchandren, R., Feldman, T. A., LaCasce, A. S., Christian, B. A., Ansell, S. M., Moskowitz, C. H., Fenton, K., Ogden, C. A., Taft, D., Zak, D. E., Sacchi, M., Galderisi, F., Herrera, A. F. Tags: 624. Hodgkin Lymphoma and T/NK Cell Lymphoma-Clinical Studies: Poster I Source Type: research

Phase 1 Study of MDR1 Inhibitor Plus Brentuximab Vedotin in Relapsed/Refractory Hodgkin Lymphoma
Conclusion:Addition of CsA to BV is safe and feasible at the MTD. The MTD was determined to be 1.8 mg/kg BV every 21 days plus 5 mg/kg of CsA PO BID on D 1-5. The ORR of 67% and CR of 33 % is very encouraging in a primary BV refractory population. The study has opened the expansion phase.Table 1.DisclosuresChen: Millennium Pharmaceuticals: Consultancy, Research Funding; Merck & Co., Inc.: Consultancy, Research Funding, Speakers Bureau; Genentech Inc.: Consultancy; Affimed: Research Funding; Seattle Genetics: Consultancy, Honoraria, Research Funding, Speakers Bureau; Pharmacyclics: Consultancy, Research Funding; Bristol...
Source: Blood - November 21, 2018 Category: Hematology Authors: Chen, R. W., Chen, L., Herrera, A. F., Mei, M., McBride, K., Abary, R., Siddiqi, T., Popplewell, L., Forman, S. J., Rosen, S. T., Kwak, L. W. Tags: 624. Hodgkin Lymphoma and T/NK Cell Lymphoma-Clinical Studies: Poster I Source Type: research

Extranodal Natural Killer/T-Cell Lymphoma Nasal Type in 87 Cases from Spain: Clinical Presentation, Treatment and Prognostic Factors. Study from the Geltamo Group
Conclusion: This is the largest series reported of Caucasian patients with ENKTL-NT. Patients are young at diagnosis and one fourth had a previous history of chronic sinusitis. This population has a poor outcome, being progression the main cause of death. Poor clinical condition at diagnosis (high ECOG PS and low albumin level) is the main factor related with poor survival. Therapies with high dose L-Asparaginase improve the survival in this western population compared with the classical CHOP regimen.DisclosuresGonzález-Barca: Roche: Speakers Bureau; Celtrion: Consultancy; Gilead: Consultancy; janssen: Consultancy, ...
Source: Blood - November 21, 2018 Category: Hematology Authors: Gonzalez-Barca, E., Martin, A., Bello, J. L., Bergua Burgues, J. M. M., Panizo, C., Encuentra, M., Monter Rovira, A., Cordoba, R., Bastos, M., Sanchez Blanco, J. J., Gomez, P., Marin Niebla, A., Gonzalez de Villambrosia, S., Sayas, M. J., Luzardo Henrique Tags: 624. Hodgkin Lymphoma and T/NK Cell Lymphoma-Clinical Studies: Poster I Source Type: research

In Situ Hybridization of HBZ and Tax in FFPE Samples from ATLL Patients and Its Association with Clinicopathological Characteristics
IntroductionAdult T-cell leukemia/lymphoma (ATLL) is a mature T-cell neoplasm caused by human T-cell leukemia virus type 1 (HTLV-1). Many studies on HTLV-1-related mRNA including HTLV-1 bZIP factor (HBZ) and Tax have been performed, mainly using cell lines, patient-derived cells, and mice. However, there are scant data concerning HTLV-1-related mRNA in formalin-fixed, paraffin-embedded (FFPE) tissue samples. We detected HBZ and Tax mRNA on FFPE tissue samples using in situ hybridization (ISH), and investigated the association with clinicopathological characteristics.Materials and methodsEighty-seven biopsy samples from new...
Source: Blood - November 21, 2018 Category: Hematology Authors: Yamada, K., Miyoshi, H., Takeuchi, M., Asano, N., Shimono, J., Arakawa, F., Nakashima, K., Sato, K., Seto, M., Ohshima, K. Tags: 624. Hodgkin Lymphoma and T/NK Cell Lymphoma-Clinical Studies: Poster I Source Type: research

Possibility of a Risk-Adapted Treatment Strategy for Untreated Aggressive Adult T-Cell Leukemia-Lymphoma (ATL) Based on the ATL Prognostic Index: A Supplementary Analysis of the JCOG9801 Study
ConclusionsGiven the very poor prognosis of ATL, our findings suggest that despite higher toxicities, mLSG15 is more suitable for the intermediate-risk group of age-adjusted ATL-PI, whereas its benefits appear modest in the low-risk group. This supplementary analysis is exploratory; therefore, a further prospective study of aggressive ATL is necessary to confirm these results.DisclosuresTsukasaki: Daiich-Sankyo: Consultancy; Ono Pharma: Consultancy; HUYA: Consultancy, Research Funding; Chugai Pharma: Honoraria, Research Funding; Eisai: Research Funding; Celgene: Honoraria; Mundy Pharma: Honoraria; Kyowa-hakko/Kirin: Honora...
Source: Blood - November 21, 2018 Category: Hematology Authors: Toyoda, K., Tsukasaki, K., Machida, R., Kadota, T., Fukushima, T., Ishitsuka, K., Maruyama, D., Nagai, H. Tags: 624. Hodgkin Lymphoma and T/NK Cell Lymphoma-Clinical Studies: Poster I Source Type: research

Superior Clinical Benefit of Brentuximab Vedotin in Mycosis Fungoides Versus Physician's Choice Irrespective of CD30 Level or Large Cell Transformation Status in the Phase 3 ALCANZA Study
Background:A histologic finding of large cell transformation (LCT) in Mycosis fungoides (MF) is often associated with an aggressive clinical course and inferior prognosis (Arulogun et al. Blood 2008). In patients (pts) with advanced MF (stage IIB-IV), LCT has been established as an independent prognostic factor (Scarisbrick et al. JCO 2015). Although CD30 expression is observed more frequently in MF with LCT vs without LCT, a wide range of CD30 expression levels is observed in LCT lesions and the level of expression lacks prognostic value for MF (Vergier et al. Blood. 2000). The ALCANZA study (NCT01578499) demonstrated sig...
Source: Blood - November 21, 2018 Category: Hematology Authors: Kim, Y. H., Prince, H. M., Whittaker, S., Horwitz, S. M., Duvic, M., Bechter, O., Sanches, J. A., Stadler, R., Scarisbrick, J., Quaglino, P., Zinzani, P. L., Wolter, P., Eradat, H., Pinter-Brown, L. C., Ortiz-Romero, P. L., Akilov, O. E., Trotman, J., Tay Tags: 624. Hodgkin Lymphoma and T/NK Cell Lymphoma-Clinical Studies: Poster I Source Type: research

Chronic Lymphocytic Leukemia (CLL) Transformed into Hodgkin Lymphoma (HL): Clinical Characteristics and Outcomes from a Large Multi-Center Collaboration
ConclusionsIn this retrospective analysis, we describe the largest reported series of pts with HT from CLL. Two-yr survival in pts with HT was shorter than what is historically expected in patients with de novo HL, but longer than what is expected in CLL pts who transform to diffuse large B-cell lymphoma. Pts with HT who have received prior CLL-directed therapies (specifically purine-analogue-based treatments) are estimated to have a shorter 2-yr OS, likely due to underlying immunosuppression. The majority of pts (61%) only received 1 line of HL therapy and only 20% went on to receive SCT (7% while in CR1), indicating that...
Source: Blood - November 21, 2018 Category: Hematology Authors: Stephens, D. M., Boucher, K., Kander, E., Parikh, S. A., Parry, E., Shadman, M., Pagel, J. M., Cooperrider, J., Rhodes, J., Mato, A. R., Winter, A. M., Hill, B. T., Gaballa, S., Danilov, A. V., Phillips, T. J., Brander, D. M., Smith, S. M., Davids, M. S., Tags: 624. Hodgkin Lymphoma and T/NK Cell Lymphoma-Clinical Studies: Poster I Source Type: research

Tax-Targeting Dendritic Cell Therapy for ATL: A Phase Ia/Ib Clinical Study
Conclusions: ATL-DC-101 was well tolerated and successfully maintained CR more than 2 years in 5/6 patients irrespective of additional mogamulizumab, indicating that this therapy could be a safe and effective long-lasting maintenance therapy even for elderly ATL patients. Currently, we are preparing Phase II trial to confirm anti-tumor effects of ATL-DC-101 monotherapy.DisclosuresShiratsuchi: Kyowa Hakko Kirin Co.Ltd: Research Funding; Chugai Pharmaceutical Co.Ltd: Research Funding; Daiichi Sankyo Co.Ltd: Research Funding. Fukuda: Chugai Pharmaceutical: Speakers Bureau. Ishida: Kyowa Hakko Kirin Co.Ltd: Honoraria, Research...
Source: Blood - November 21, 2018 Category: Hematology Authors: Shiratsuchi, M., Fukuda, T., Iino, T., Hasegawa, A., Yasunaga, J.-i., Watanabe, K., Hirata, A., Utsunomiya, H., Ohno, H., Ishida, T., Akashi, K., Matsuoka, M., Kannagi, M., Suehiro, Y. Tags: 624. Hodgkin Lymphoma and T/NK Cell Lymphoma-Clinical Studies: Poster I Source Type: research

PD-1 Blockade with Pembrolizumab for Classical Hodgkin Lymphoma after Autologous Stem Cell Transplantation
Conclusions: Pembrolizumab administered after ASCT in patients with R/R cHL has a safety profile that appears similar to its use in the R/R setting, although possibly with a higher rate of neutropenia. The 18-month progression-free rate in this high-risk cohort compares favorably with previous published studies, and supports the hypothesis that PD-1 blockade in this setting may increase the efficacy of ASCT. This should be tested in a randomized trial.Figure.DisclosuresArmand: Pfizer: Consultancy; Affimed: Consultancy, Research Funding; Otsuka: Research Funding; Merck: Consultancy, Research Funding; Infinity: Consultancy; ...
Source: Blood - November 21, 2018 Category: Hematology Authors: Armand, P., Chen, Y.-B., Redd, R. A., Joyce, R. M., Bsat, J., Merryman, R. W., Coleman, K., Dahi, P. B., Nieto, Y., LaCasce, A. S., Fisher, D. C., Ng, S. Y., Odejide, O. O., Freedman, A. S., Kim, A. I., Crombie, J. L., Jacobson, C. A., Jacobsen, E. D., Wo Tags: 624. Hodgkin Lymphoma and T/NK Cell Lymphoma-Clinical Studies: Poster I Source Type: research

Adct-301 (Camidanlumab Tesirine), a Novel Pyrrolobenzodiazepine-Based CD25-Targeting Antibody Drug Conjugate, in a Phase 1 Study of Relapsed/Refractory Non-Hodgkin Lymphoma Shows Activity in T-Cell Lymphoma
Conclusions: In pts with R/R NHL, active doses of Cami-T with acceptable safety profiles were identified for both B-cell and T-cell lymphoma during dose escalation of this study. Five out of the 10 pts on study with T-cell lymphoma treated in the 60, 80, or 100 µg/kg cohorts responded. Subtype-specific cohorts in the dose escalation portion of this study are underway to better define the recommended dose for expansion.Study sponsored by ADC Therapeutics. http://clinicaltrials.gov/show/NCT02432235.DisclosuresCollins: MSD: Consultancy, Honoraria; ADC Therapeutics: Consultancy, Honoraria, Research Funding; Roche: Consul...
Source: Blood - November 21, 2018 Category: Hematology Authors: Collins, G. P., Horwitz, S. M., Davies, A., Karnad, A., Samaniego, F., Spira, A. I., Fields, P. A., Menne, T., Boni, J., Cruz, H., Feingold, J., He, S., Wuerthner, J., Hamadani, M. Tags: 624. Hodgkin Lymphoma and T/NK Cell Lymphoma-Clinical Studies: Poster I Source Type: research

A Novel Patient-Derived Xenograft Model of Secondary CD20- CNS Lymphoma for Mechanistic and Therapeutic Exploration
IntroductionThe majority of secondary central nervous system (CNS) lymphoma cases are derived from histologically high-grade systemic lymphomas such as diffuse-large B cell lymphoma (DLBCL) and Burkitt's lymphoma. These CNS lymphomas are associated with poor prognosis and a low likelihood of long-term survival, especially rituximab-ineffective CD20- lymphoma. To investigate the biological features and potential therapeutic targets of CNS-involved CD20- lymphoma, we established the first known patient-derived xenograft (PDX) model using cerebrospinal fluid (CSF).MethodsSix- to 8-week-old male NSG mice (Jackson Laboratory) w...
Source: Blood - November 21, 2018 Category: Hematology Authors: Zhang, L., Zhang, H., Guo, H., Sun, Y., Feng, N., Marszalek, J. R., Ahmed, M., Nomie, K., Wang, M. Tags: 625. Lymphoma: Pre-Clinical-Chemotherapy and Biologic Agents: Poster I Source Type: research

Efficacy and Toxicity of JCAR014 in Combination with Durvalumab for the Treatment of Patients with Relapsed/Refractory Aggressive B-Cell Non-Hodgkin Lymphoma
ConclusionThe combination of JCAR014 with durvalumab for the treatment of adult pts with aggressive B-cell NHL appears safe; however, dose escalation is ongoing. Complete responses were observed both at initial restaging after JCAR014 infusion, and also subsequently in pts continuing durvalumab therapy after initially failing to achieve CR.DisclosuresHirayama: DAVA Oncology: Honoraria. Hay: DAVA Oncology: Honoraria. Till: Mustang Bio: Patents & Royalties, Research Funding. Kiem: Homology Medicine: Consultancy; Magenta: Consultancy; Rocket Pharmaceuticals: Consultancy. Shadman: Verastem: Consultancy; Beigene: Research F...
Source: Blood - November 21, 2018 Category: Hematology Authors: Hirayama, A. V., Gauthier, J., Hay, K. A., Sheih, A., Cherian, S., Chen, X., Pender, B. S., Hawkins, R. M., Vakil, A., Steinmetz, R. N., Phi, T.-D., Chapuis, A. G., Till, B. G., Kiem, H.-P., Shadman, M., Cassaday, R. D., Acharya, U. H., Riddell, S. R., Ma Tags: 626. Aggressive Lymphoma (Diffuse Large B-Cell and Other Aggressive B-Cell Non-Hodgkin Lymphomas)-Results from Prospective Clinical Trials: Poster I Source Type: research