In the summer of 2015, Weill Cornell Medical College and Cellectis, a French pharmaceutical company, announced a translational research collaboration for a new allogeneic chimeric antigen receptor T cell therapy called UCART123. This “off-the-shelf” product is a directed immunotherapy for patients with acute myeloid leukemia (AML), an aggressive blood cancer. T cells are harvested from healthy donors and engineered to target the CD123 antigen, which is found on AML blast and stem cells, as well as tumor cells in another aggressive malignancy, blastic plasmacytoid dendritic cell neoplasm (BPDCN).
The clinical trial of UCART123 in AML is being led by principal investigator Dr. Gail J. Roboz, Professor of Medicine and Director of the Leukemia Program at Weill Cornell Medicine and NewYork-Presbyterian. Translational scientific studies for the trial are being conducted in the laboratory of Dr. Monica Guzman, Associate Professor of Pharmacology in Medicine, also at Weill Cornell. Clinical research on UCART123 in BPDCN will be led by Dr. Naveen Pemmaraju and Dr. Hagop Kantarjian at the MD Anderson Cancer Center in Houston, Texas.
Stay tuned for more updates regarding the new phase 1 clinical trial for UCART123 to be initiated here at the Leukemia Program in the coming months.
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.
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.
#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
#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
#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
#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
#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
#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
#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
#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
#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
#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
#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
Earlier this week the U.S. News and World Report released their annual survey of “Best Hospitals”. NewYork-Presbyterian one of the country’s largest and most comprehensive hospitals was ranked New York’s No. 1 hospital for the 16th year in a row, and No. 6 ranked hospital in all of the United States. Dr. Augustine M.K. Choi, interim dean of Weill Cornell Medicine commented,
“Our esteemed physicians and scientists at Weill Cornell Medicine and NewYork-Presbyterian/Weill Cornell Medicine always put patients first, providing them with the finest, most comprehensive care so that they can live their healthiest lives. Together we create one of the top academic medical centers in the United States, motivated by a shared commitment: to drive excellence in healthcare and truly make a difference in New York and beyond.”
This commitment is shared by the physicians, researchers, and staff in the Leukemia Program.
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]
In many ways, it’s a science success story: 8-year-old boy with a rare form of brain cancer is treated by one of the world’s leading experts in the disease, who collaborates with a pioneering precision medicine institute to sequence his cancer and create a first-of-its-kind tumor model replica in the lab, allowing for further analysis and treatment testing without risk of harm to the child.
Upon analysis, the physician-scientist discovers a mutation previously not known to be linked to that type of cancer — and it happens to be in the protein that his colleague has spent a career studying. He contacts the colleague to ask if there is a drug to target the protein, and it arrives the next day. Applied to the tumor model, the drug effectively kills 80-90 percent of the diseased cells.
If only the story ended there.
Unfortunately, although the drug has been approved by the FDA, it cannot be used on the young patient because it has never been tested in children, and the pharmaceutical company controlling the drug is not willing to take the risk.
“We now start the gymnastics of trying to get permission from the FDA based on compassionate use,” said Jeffrey Greenfield, M.D., Ph.D. “We’ve done it before, and it takes anywhere from 3-6 months. This boy doesn’t have 3-6 months.”
Greenfield, a neurosurgeon at Weill Cornell Medicine and NewYork-Presbyterian, shared the anecdote at a special event held at Weill Cornell Medicine on June 29, one of 270 across the United States convened by Vice President Joe Biden in tandem with a national summit at Howard University in Washington, DC
Biden invited regional participants to discuss the goals of the “Cancer Moonshot” mission, announced in January by President Barack Obama as a way to accelerate cancer research, foster data sharing and collaboration, and improve patient access to care — all on a five-year timeline.
Greenfield said his story summed up some of the challenges the nation will face in trying to achieve such an ambitious goal.
“The promise of precision medicine, which is enormous and which we have all bought into, doesn’t deliver in this case,” Greenfield said. “We’ve done all the work that we’ve promised to do, and we still have hurdles. The science is great, the medicine is great, but we’ve got to figure out a way to bridge the chasm between academia, pharma and clinic.”
The future is now
Greenfield was joined at the event by more than a dozen other distinguished researchers and physicians, as well as a standing-room only crowd of around 100.
Participants heard that in many ways, the future of medicine is already here. Silvia Formenti, M.D., discussed how she uses radiation therapy to turn patients’ own tumors into internal “vaccines,” and Ching Tung, Ph.D., director of the Molecular Imaging Innovations Institute described new ways of “seeing” cancer.
Neurosurgeon Mark Souweidane, M.D., spoke about the importance of developing new forms of drug delivery and working with industry to be able to integrate research and technology into the operating room. His colleagues Susan Pannullo, M.D., and Michael Kaplitt, M.D., Ph.D., explained stereotactic radiosurgery and the use of ultrasound technology to poke holes in the blood-brain barrier.
“These are ways we can use novel non-invasive technologies that will put us as surgeons out of business, unfortunately, but will help heal the world,” Kaplitt said.
“The idea isn’t new, “Roboz said. “What’s new is that we can actually do it, we are able to finally do things that were Jetsons level before.”
“In 2016, we are at an amazing inflection point in cancer therapy,” added neurosurgeon Rohan Ramakrishna, M.D. “It’s one thing to say you want to accomplish big change in five years, it’s another to be able to do that.”
But he added that the time it takes to get discoveries from bench to bedside is still too long. We need to innovate, Ramakrishna said, and we need to incentivize high-risk research.
To read the full story [go]