City of Hope Physicians Present New CAR-T Cell Therapy Study Results and Other Research at 2017 American Society of Hematology Annual Meeting

Clinical trials for non-Hodgkin lymphoma, acute myeloid leukemia and myelofibrosis could improve outcomes for patients

(Note: Updated study results will be presented at the ASH meeting. Journalists are asked to honor ASH’s embargo policy, which states that data from these trials cannot be published or broadcast until presentation has taken place.)

DUARTE, Calif.--()--Research about clinical trials that lay the groundwork for novel non-Hodgkin lymphoma, acute myeloid leukemia and two rare blood cancers, myelofibrosis and blastic plasmacytoid dendritic cell neoplasm (BPDCN), will be among the highlights of the annual meeting of the American Society of Hematology (ASH) in Atlanta, Dec. 9 to 12. The trials, presented by City of Hope physicians and researchers, could ultimately lead to innovative therapeutic approaches that improve treatment options and quality of life for patients with blood cancers and other diseases.

The ASH meeting, which will host more than 25,000 hematology professionals focused on research and treatment for blood cancers and other diseases, encourages clinicians and scientists working both ends of the bench-to-bedside translational research spectrum to discuss the latest studies.

“By participating in the annual ASH meeting, City of Hope doctors and researchers highlight our leading-edge research efforts that can lead to more treatment options, including CAR-T cell therapy, against devastating blood cancers and other hematological diseases,” said Stephen J. Forman, M.D., leader of City of Hope’s Hematologic Malignancies and Stem Cell Transplantation Institute and the Francis & Kathleen McNamara Distinguished Chair in Hematology and Hematopoietic Cell Transplantation. “We are looking forward to sharing our latest research findings and continuing our commitment to advancing the most promising cures against cancers, including finding new targets in CAR-T cell therapy.”

“City of Hope’s work doesn’t stop there – we are working around the clock to continue to advance our evolving and pioneering work in such fields as stem cell and bone marrow transplantation,” Forman added.

Among the research presented by City of Hope scientists will be results of four clinical trials that lay the groundwork for new clinical treatments for patients with non-Hodgkin lymphoma, acute myeloid leukemia, myelofibrosis and BPDCN. Those studies address:

Remissions using CAR-T cell therapy for acute myeloid leukemia (AML), BPDCN

Patients whose AML has returned or is no longer responding to treatment have few therapeutic options; only a minority of those patients can receive an allogeneic hematopoietic stem cell transplantation, which can potentially cure AML. BPDCN is a rare blood cancer with a low median survival rate and no standard of care.

More treatment options for these patients are needed, and a new CAR-T cell therapy developed at City of Hope targets CD123 cells, which is overexpressed on AML blasts and BPDCN cells.

Led by Elizabeth Lihua Budde, M.D., Ph.D., assistant professor in City of Hope Department of Hematology & Hematopoietic Cell Transplantation, City of Hope patients are enrolled in the first-in-human phase 1 dose escalation clinical trial, whose primary objective is to test the safety and activity of escalating doses of CD123 CAR-T cells.

The study demonstrated that CD123 CAR-T cells are feasible and safe to use in both AML and BPDCN patients. Some of the AML patients had a complete response to the treatment, meaning their cancer regressed; this enabled them to continue with a transplant. Side effects for some patients included cytokine release syndrome (an elevated amount of cytokines are released into the body due to an overabundance of T cells, causing a high fever and other health complications). Cytokine release syndrome and other side effects were treatable.

A 74-year-old City of Hope patient with BPDCN achieved a complete response to the CAR-T cell therapy for at least 60 days and showed no serious side effects from the treatment.

Budde will report final results for the study on Monday, Dec. 11, at 4:30 p.m. EST; study results are embargoed until then.

JCAR017, CAR-T cell therapy for B cell non-Hodgkin lymphoma

Tanya Siddiqi, M.D., assistant clinical professor in City of Hope’s Department of Hematology & Hematopoietic Cell Transplantation, will report on patient characteristics and biomarkers in the first multicenter phase 1 trial of JCAR017, a CAR-T cell therapy that targets CD19 cells in refractory/relapsed aggressive B cell non-Hodgkin lymphoma (NHL). As previously reported, JCAR017 has demonstrated high complete remission rates, which indicates that the cancer has disappeared, and a low incidence of cytokine release syndrome (a severe hyper-inflammatory reaction to the therapy) and neurotoxicity (which affects the nervous system.)

Data from the trial was analyzed to help identify patients who might respond better to JCAR017 treatment and have fewer side effects.

Preliminary results demonstrate that patients whose NHL had progressed, causing a severe inflammatory state (infections and other health complications) and a high tumor burden (which refers to a high number of cancer cells or tumors) prior to JCAR017 treatment had an increased risk for toxicity after receiving the therapy.

Patients with both a low tumor burden and inflammatory state appear to have less toxicity and a positive, more sustained response to JCAR017.

These data suggest that treating patients earlier in their course of therapy, or using a panel of clinical and laboratory biomarkers to help identify patients for potential early intervention, is feasible and may help reduce health complications and potentially improve durability of response.

The trial included patients from City of Hope, Massachusetts General Hospital, Memorial Sloan Kettering Cancer Center, Northwestern University's Robert H. Lurie Comprehensive Cancer Center, University of Nebraska Medical Center, Harvard Medical School's Beth Israel Deaconess Medical Center, M.D. Anderson Cancer Center, University of Alabama at Birmingham and Fred Hutchinson Cancer Research Center.

Updated results from Siddiqi’s study will be presented at the ASH conference on Saturday, Dec. 9, at 2 p.m.; results from this trial are embargoed until then.

A study on treating myelofibrosis patients with the FluMel regimen

Assistant Clinical Professor Haris Ali, M.D., and Associate Chair David S. Snyder, M.D., both in City of Hope’s Department of Hematology & Hematopoietic Cell Transplantation, will present their team’s research on the largest single cancer center study examining the effects of the fludarabine/melphalan (FluMel) regimen, a chemotherapy, in City of Hope allogeneic transplant patients with myelofibrosis, a rare bone marrow cancer.

The overall survival rate after five years was nearly 65 percent for all patients in this study.

Patients with the best overall survival rates were those who received a stem cell donation from a related donor, or 80 percent. But even patients who had an unrelated donor fared well with a 65 percent survival rate after five years.

Updated findings from the study will be presented on Saturday, December 9, at 2 p.m.; study results are embargoed until then.

City of Hope research on a new CAR-T therapy, BAFF-R

There is an urgent need for improved novel CAR T-cell therapies directed at new targets. One potential target is the B cell activating factor receptor (BAFF-R), a protein which is primarily expressed on B cells and various subtypes of B cell non-Hodgkin lymphoma (NHL) and acute lymphoblastic leukemia (ALL). A recent Clinical Cancer Research journal article detailed how City of Hope researchers have developed a therapeutic BAFF-R antibody with strong anti-B cell tumor activity that has been tested in a preclinical study.

Led by Hong Qin, Ph.D., associate research professor in the City of Hope Department of Hematology & Hematopoietic Cell Transplantation, and Larry Kwak, M.D., Ph.D., Dr. Michael Friedman Professor in Translational Medicine and director of the Toni Stephenson Lymphoma Center, the study demonstrated that BAFF-R CAR-T cells had a high level of efficacy against B-cell malignancies.

Researchers compared different types of T cells for their growth and effectiveness in vivo. Naïve T cell starting products, which refers to the original T cells that were then duplicated, generated sufficient numbers of T cells central memory and T cells memory stem CAR-T cells for anti-tumor activity. The BAFF-R CAR-T cell treatment demonstrated long-term tumor free survival in animal models compared to the CD19 CAR-T cell treated cohort, which demonstrated delayed tumor growth.

Targeting BAFF-R, combined with a strategy to improve CAR-T cell persistence, potentially addresses unmet clinical needs in B cell NHLs and ALL, particularly in the setting of CD19 CAR-T-resistant or CD19-negative relapsed disease.

Qin will present final study results during a poster session on Sunday, Dec. 10, from 6 to 8 p.m.; study results are embargoed until then.

About City of Hope

City of Hope is an independent research and treatment center for cancer, diabetes and other life-threatening diseases. Designated as one of only 49 comprehensive cancer centers, the highest recognition bestowed by the National Cancer Institute, City of Hope is also a founding member of the National Comprehensive Cancer Network, with research and treatment protocols that advance care throughout the world. City of Hope is located in Duarte, California, just northeast of Los Angeles, with community clinics throughout Southern California. It is ranked as one of "America's Best Hospitals" in cancer by U.S. News & World Report. Founded in 1913, City of Hope is a pioneer in the fields of bone marrow transplantation, diabetes and numerous breakthrough cancer drugs based on technology developed at the institution. For more information about City of Hope, follow us on Facebook, Twitter, YouTube or Instagram.


City of Hope
Letisia Marquez

Release Summary

City of Hope research on blood cancers will be presented at the annual meeting of the American Society of Hematology (ASH).


City of Hope
Letisia Marquez