FDA Approves CAR T-Cell Therapy for Kids and Young Adults with Acute Lymphoblastic Leukemia

On August 30, 2017, the United States Food and Drug Administration (FDA) approved the cell-based gene therapy Kymriah for treatment of children and young adults with a certain form of acute lymphoblastic leukemia (ALL), the most common childhood cancer in America. The approval greenlights the first gene therapy to be made available in the United States.

Each dose of Kymriah is customized to the individual patient by way of an emerging form of immunotherapy called chimeric antigen receptor (CAR) T-cell therapy. T-cells are extracted from the patient’s blood and genetically modified in the laboratory to produce chimeric antigen receptors, surface-level proteins that enable the T-cells to recognize and fight leukemia cells that possess the antigen CD19. The newly engineered T-cells are then infused back into the patient’s body. The goal of Kymriah and other forms of immunotherapy is to target and attack the cancer cells that they are programmed to destroy.

This historic approval follows clinical trials demonstrating durable safety and efficacy in children and young adults up to age 25 with relapsed or refractory B-cell precursor ALL.

Weill Cornell Medicine and NewYork-Presbyterian Hosptial has ongoing clinical trials evaluating CAR T-cell therapy in adults with certain forms of leukemia. To learn more, visit: https://jcto.weill.cornell.edu/.


New Classifications for Myelodysplastic Syndromes (MDS)

Dr. Ellen Ritchie recently participated in an OncLive discussion on the latest modifications to the World Health Organization (WHO) classification of Myelodysplastic Syndromes (MDS). WHO classification is the standard diagnostic system utilized by medical institutions worldwide, including here at Weill Cornell Medicine. Recent advances in our understanding of the biological course of MDS have warranted revision to its WHO classification, which was last updated in 2008. In particular, mutational and cytogenetic analyses have to led to refinement of diagnostic terms for MDS. These modifications include a distinction between single versus multilineage dysplasia and elimination of the term “cytopenia.”

The OncLive discussion centered on implications of the new classification on the prognosis and treatment of MDS. While the WHO classification is just one of many factors to consider when evaluating the prognosis of the disorder, the panelists agree that the new modifications will make it easier to determine an appropriate course of treatment for their patients. To learn more, click here or watch the video below.


Weill Cornell Leukemia Program Abstracts @ ASH 2016

December is an exciting month here at the Leukemia Program, as each year, our doctors and researchers are invited to attend and present their work at the annual meeting of the American Society of Hematology (ASH). This important meeting provides the opportunity to network with thousands of hematology specialists from all over the world.

This year, the 58th ASH Annual Meeting & Exposition is being held December 3-6 in San Diego, California. We are very proud to play an integral role in research that is changing the way leukemia is diagnosed, tracked and treated. The below abstracts are being presented in oral or poster sessions by the Leukemia Program’s physicians, researchers, and collaborators.

AML

#98. Results of a Clinical Study of Pevonedistat (Pev), a First-in-Class NEDD8-Activating Enzyme (NAE) Inhibitor, Combined with Azacitidine (Aza) in Older Patients (Pts) with Acute Myeloid Leukemia

#226. A Randomized Phase II Study of Low-Dose Decitabine Versus Azacitidine in Patients with Low- or Intermediate-1-Risk Myelodysplastic Syndromes: A Report on Behalf of the MDS Clinical Research Consortium

#433. Cooperative Epigenetic Remodeling By TET2 Loss and NRAS Mutation Drives Myeloid Transformation and MEK Inhibitor Sensitivity

#438. BCL6 Is Critical to Overcome Oncogene-Induced Senescence in RAS-Mediated B Cell Transformation

#582. Acute Myeloid Leukemia Cells Resist Chemotherapy through a Reversible Senescence-like State Maintaining Repopulation Potential

#599. Changes of the Mutational Landscape in Relapsed Acute Myeloid Leukemia

#765. Allogeneic Tcrα/β Deficient CAR T-Cells Targeting CD123 Prolong Overall Survival of AML Patient-Derived Xenografts

#902. Analysis of Efficacy By Age for Patients Aged 60–75 with Untreated Secondary Acute Myeloid Leukemia (AML) Treated with CPX-351 Liposome Injection Versus Conventional Cytarabine and Daunorubicin in a Phase III Trial Clinically Relevant Abstract

#903. Durable Overall Survival Benefit in Patients ≥ 60 Years with Relapsed or Refractory AML Treated with Vosaroxin/Cytarabine Vs Placebo/Cytarabine: Updated Results from the Valor Trial

#904. Long Term Survival and Clinical Complete Responses of Various Prognostic Subgroups in 103 Relapsed/Refractory Acute Myeloid Leukemia (r/r AML) Patients Treated with Guadecitabine (SGI-110) in Phase 2 Studies

#906. Survival Following Allogeneic Hematopoietic Cell Transplantation in Older High-Risk Acute Myeloid Leukemia Patients Initially Treated with CPX-351 Liposome Injection Versus Standard Cytarabine and Daunorubicin: Subgroup Analysis of a Large Phase III Trial

#1048. Cooperative Gene Repression By DNA Methylation and LSD1-Mediated Enhancer Inactivation in Acute Myeloid Leukemia

#1063. The Use of Hypomethylating Agents (HMAs) in Patients with Relapsed and Refractory Acute Myeloid Leukemia (RR-AML): Clinical Outcomes and Their Predictors in a Large International Patient Cohort

#1069. Final Results of the Chrysalis Trial: A First-in-Human Phase 1/2 Dose-Escalation, Dose-Expansion Study of Gilteritinib (ASP2215) in Patients with Relapsed/Refractory Acute Myeloid Leukemia

#1070. Determination of IDH1 Mutational Burden and Clearance Via Next-Generation Sequencing in Patients with IDH1 Mutation-Positive Hematologic Malignancies Receiving AG-120, a First-in-Class Inhibitor of Mutant IDH1

#1077. CD97 Is a Critical Regulator of Acute Myeloid Leukemia Stem Cell Function

#1553. PI3 Kinase p110 Delta Is Required for Leukemic Cell Survival and Self-Renewal in t(8;21) Acute Myeloid Leukemia

#1680. Genetic Determinants of Response to Guadecitabine (SGI-110) in AML

#1693. Selection and Characterization of Antibody Clones Are Critical for Accurate Flow Cytometry-Based Monitoring of CD123 in Acute Myeloid Leukemia

#2011. Comprehensive Analysis of Safety: Rigosertib in 557 Patients with Myelodysplastic Syndromes (MDS) and Acute Myeloid Leukemia

#2816. Thioguanine Combined with Decitabine Can Overcome Resistance to Hypomethylating Agents: Final Results of a Phase I Trial of a Pharmacodynamically-Conceived Thioguanine/Decitabine Combination in Patients with Advanced Myeloid Malignancies

#2888. Minimal Residual Disease Assessment of Common and Rare NPM1 Mutations Using a Single Massively Multiplex Digital PCR Assay

#3548. Current Diagnosis Patterns for Acute Myeloid Leukemia (AML) in Clinical Practice Compared with World Health Organization (WHO) 2008 Recommendations: Outcomes from the CONNECT® Myelodysplastic Syndromes (MDS) and AML Disease Registry

#4039. Pre-Clinical Studies of Anti-CD123 CAR-T Cells for the Treatment of Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN)

ALL

#279. The Pro-Tumorigenic Vascular Niche Sustains the T-Cell Acute Lymphoblastic Leukemia Phenotype and Fosters Resistance to Therapy

#907. Oncogenic Feedback Activation Between BCL6 and MLL Promotes Malignant Transformation in MLL-Rearranged Acute Lymphoblastic Leukemia

#1629. A Pediatric-Inspired Regimen Containing Multiple Doses of Intravenous Pegylated Asparaginase Appears Safe and Effective in Newly Diagnosed Adult Patients with Ph-Negative Acute Lymphoblastic Leukemia in Adults up to Age 60: Results of a Multi-Center Phase II Clinical Trial

#4088. CD25 Enables Oncogenic BCR Signaling and Represents a Therapeutic Target in Refractory B Cell Malignancies

CML

#3090. ENESTgoal Treatment-Free Remission Study: Updated Preliminary Results and Digital Polymerase Chain Reaction Analysis in Patients with Chronic Myeloid Leukemia in Chronic Phase Who Switched from Imatinib to Nilotinib

MPN

#479. Interim Analysis of the Myeloproliferative Disorders Research Consortium (MPD-RC) 112 Global Phase III Trial of Front Line Pegylated Interferon Alpha-2a Vs. Hydroxyurea in High Risk Polycythemia Vera and Essential Thrombocythemia

#4271. Impact on MPN Symptoms and Quality of Life of Front Line Pegylated Interferon Alpha-2a Vs. Hydroxyurea in High Risk Polycythemia Vera and Essential Thrombocythemia: Interim Analysis Results of Myeloproliferative Disorders Research Consortium (MPD-RC) 112 Global Phase III Trial

MDS

#112. Frequency and Prognostic Significance of Cytogenetic Abnormalities in 1269 Patients with Therapy-Related Myelodysplastic Syndrome – a Study of the International Working Group (IWG-PM) for Myelodysplastic Syndromes

#297. Is Serial Monitoring of Myeloid Mutations Clinically Relevant in Myelodysplastic Syndromes (MDS): A Report on Behalf of the MDS Clinical Research Consortium (CRC)

#343. Enasidenib (AG-221), a Potent Oral Inhibitor of Mutant Isocitrate Dehydrogenase 2 (IDH2) Enzyme, Induces Hematologic Responses in Patients with Myelodysplastic Syndromes

#964. Runx1 Deficiency and MDS-Associated U2af1 Mutation Cooperate for Leukemia Development in a New Mouse Model

#2011. Comprehensive Analysis of Safety: Rigosertib in 557 Patients with Myelodysplastic Syndromes (MDS) and Acute Myeloid Leukemia (AML)

#4321. Ring Sideroblasts and SF3B1 Mutations in Myelodysplastic Syndromes (MDS): Are They Two Faces of the Same Coin? a Study on Behalf of the MDS Clinical Research Consortium (MDS CRC)

#4322. Optimal Treatment Order of Lenalidomide and Hypomethylating Agents for Lower-Risk Myelodysplastic Syndromes: A Report on Behalf of the MDS Clinical Research Consortium

#4332. Importance of Complete Remission on Predicting Overall Survival in Patients with Lower-Risk Myelodysplastic Syndromes


Cancer Care: The Next Generation

Dr. Gail Roboz on ABC talks about “taking a chance on something new.” [go]

 

 

 

 

 


Treatment of minimal residual disease in AML patients

 

Gail Roboz, MD from Weill Cornell Medicine discusses minimal residual disease (MRD) found in acute myeloid leukemia (AML) patients. According to Dr Roboz the biology of the remaining leukemia cells may not be similar to the bulk disease that was eliminated with initial therapy. Currently there are efforts to characterize and quantify the remaining cells, with the hopes to determine whether existing or novel treatments can be used to lower their number to below the threshold level required for stem cell transplants. Furthermore, stem cell transplants are dramatically less effective if there is minimal residual disease detected so any therapy to reduce these cells may confer an advantage. Recorded at the 2016 Annual Meeting of the British Society of Haematology (BSH) and International Society of Hematology (ISH), in Glasgow, Scotland.

Original story posted to Video Journal of Hematological Oncology [go]


Dr. Pinkal Desai Discusses a Clinical Trial of SGI-110 for People with MDS/MPN and CMMoL

This clinical study is aimed at men and women with a diagnosis of: Chronic Neutrophilic Leukemia (CNL), Chronic Myelomonocytic Leuekmia (CMML), atypical Chronic Myeloid Leukemia (aCML), Juvenile Myelomonocytic Leukemia (JMML), and Myelodysplastic & Myeloproliferative Neoplasm Unclassifiable (MDS/MPN-U). Click here to learn more or see if you are eligible to participate.


Phase 3 Trial Shows CPX-351 (Vyxeos) Boosts Overall Survival in AML

Frontline treatment with CPX-351 (Vyxeos) significantly boosted overall survival (OS) for older patients with high-risk, secondary acute myeloid leukemia (AML) when compared with the current standard of care, cytarabine and daunorubicin, according to data from a phase III trial released by the drug’s developer, Celator Pharmaceuticals, Inc.
“These findings confirm that Vyxeos provides the first opportunity we’ve had in decades to extend survival for patients with high-risk AML,” added Gail Roboz, MD, Professor of Medicine and Director of the Leukemia Program at the Weill Medical College of Cornell University and the New York-Presbyterian Hospital in New York, said in a statement. “Also, more patients in remission means more who are eligible for potentially curative therapy.” To see the full article and data visit Targeted Oncology