John Theurer Cancer Center Investigators Present Pioneering Research at the American Society of Hematology Annual Conference

Findings Continue to Change the Treatment of Blood Cancers

Newswise — Researchers from Hackensack Meridian Health John Theurer Cancer Center (JTCC), a part of the Georgetown Lombardi Comprehensive Cancer Center, will present updates on treatment advances in multiple myeloma, lymphoma, leukemia, and bone marrow transplantation at the 63rd American Society of Hematology (ASH) Annual Meeting and Exposition, to be held virtually and live at the Georgia World Congress Center in Atlanta from December 11-14, 2021.

"John Theurer Cancer Center is a world leader in the care of people with hematologic malignancies and a pioneer in clinical research related to blood cancers. The acceptance of 47 studies from our investigators demonstrates our expertise in this area and our commitment to improving outcomes not only for our own patients, but people affected by these diseases everywhere," said Andre Goy, MD, MS, chairman and executive director of the John Theurer Cancer Center.

This year's presentations will include a plenary session as the #2 ranked abstract for the entire conference with data that will change the paradigm in the treatment of relapsed aggressive lymphoma for the FIRST TIME in 40 years. Dr. Lori Leslie, MD, director of the Indolent Lymphoma and Chronic Lymphocytic Leukemia Research Programs at JTCC will be co-presenter of the phase III international ZUMA-7 clinical trial (abstract #2), which compared axicabtagene ciloleucel (axi-cel) CAR T-cell therapy with standard of care (SOC) in patients with relapsed / refractory diffuse large B-cell lymphoma (DLBCL) after initial therapy. For decades the SOC has been high dose therapy followed by autologous stem cell transplant (ASCT) – but patients with high risk disease and / or early relapse still do very poorly. Axi-cel is now used to treat DLBCL that have failed two prior regimens of treatment, including standard salvage chemoimmunotherapy (CIT) followed by ASCT. 

Bringing axi-cel earlier as second line therapy resulted in a 2.5-fold increase in median event-free survival (defined as the time without any cancer progression or any related complications)  and doubled the complete response rate (65% vs 32%).

"This study is the first to change the paradigm for relapsed and refractory DLBCL that was established decades ago, demonstrating significant and clinically meaningful improvements in outcome," said Dr. Leslie. "Axi-cel may replace chemoimmunotherapy and autologous stem cell transplantation as the standard of care for people with DLBCL that relapses or persists after initial treatment. It is a game-changer."

The JTCC presentations address new developments in the treatment of multiple myeloma, lymphoma, leukemia, and bone marrow transplantation, as well as a study assessing gene therapy for sickle cell disease in pediatric patients.

Multiple Myeloma Research

• Adding a PI3K inhibitor improved duration of CAR T-cell response. (Abstract #548, David S. Siegel, MD, PhD) In this phase I clinical trial, researchers showed that adding a PI3 kinase inhibitor called bb007 to bb2121 CAR T-cell therapy (forming a combined therapy called bb21217) in relapsed/refractory multiple myeloma (MM) patients who had three or more regimens of treatment resulted in a duration of response of 17 months (compared with 10 months for bb2121 alone in a prior study), and CAR T cells were detectable longer.
• Study shows feasibility of "off the shelf" donated CAR T cells. (Abstract #651, David S. Siegel, MD, PhD). Current CAR T-cell therapies involve expensive modification of a patient's own T cells. Allogeneic (donated) CAR T cells represent a potentially more accessible, less expensive option but carry the risk of rejection and complications such as graft-vs-host disease. The phase I UNIVERSAL study demonstrated the safety of donated anti-BCMA CAR T cells in heavily pretreated MM patients, with mild to moderate side effects as expected for this type of immunotherapy.
• Novel targeted MM therapies. Three abstracts provided additional data on novel targeted agents for relapsed/refractory MM. Selinexor was FDA approved in December 2020 and is being assessed in combination with other agents. A study of once-weekly oral selinexor with pomalidomide and dexamethasone (abstract #2748, Noa Biran, MD) showed an overall response rate of more than 60% in relapsed/refractory MM, including patients whose disease persisted after CAR T-cell therapy or after anti-CD38 antibody treatment. This is important because patients with MM after CAR T-cell therapy usually do not respond to additional treatment.
• Study shows patients fare better if treated in high-volume academic medical centers. (Abstract #2996, David Vesole, MD, PhD, with Lombardi Comprehensive Cancer Center researchers) An analysis of data from the National Cancer Database of nearly 175,000 patients with MM treated at all types of facilities showed that the median overall survival was 75.5 months at high-volume centers versus 50.2 months at low-volume centers. Academic/research cancer programs with high volumes have the best outcomes in MM and are more likely to use chemotherapy, immunotherapy, and autologous stem cell transplantation than low-volume centers, particularly community cancer centers.

Lymphoma Research

• Long-term data confirm durability of CAR T-cell benefit in indolent lymphoma. (Abstract #93, Lori Leslie, MD) An update of the pivotal ZUMA-5 clinical trial, which led to the approval of axi-cel CAR T-cell therapy for relapsed/refractory follicular lymphoma, confirmed continued benefit in patients with indolent lymphoma. In follicular lymphoma (most common subtype of indolent lymphoma), high response rates translated to durable responses, with a median duration of response of 38.6 months and 57% of patients free of cancer progression at last follow-up.
• Study confirms benefit of CAR T-cell therapy for mantle cell lymphoma (MCL). (Abstract #744, Andre Goy, MD) ZUMA-2 led to the first approval of CAR T-cell therapy for MCL. An analysis of real-world data of MCL patients who received this treatment, 73% of whom would not have been eligible for ZUMA-2, demonstrated similar effectiveness, with an overall response rate of 86% and 64% achieving a complete response. The results support the paradigm-shifting benefit of this therapy in a heavily pretreated patient population where the median overall survival would have otherwise been very poor.
• Molecular biomarkers predictive of CAR T-cell response. (Abstract #165, Andrew Ip, MD, Andre Goy, MD) Researchers performed whole exome and transcriptome sequencing to show that patients with DLBCL who had genetic signatures of high-risk disease with standard initial therapy do well with CAR T-cell therapy. Some mutations predicted good versus poor outcomes after CAR T-cell therapy—reflecting differences in the tumor or its microenvironment—and may provide the rationale for choosing the most appropriate treatment for each patient and augmenting the response to CAR T-cell therapy.
• Value of adding brentuximab to standard chemotherapy for peripheral T-cell lymphoma (Abstract #133, Tatyana Feldman, MD, Lori Leslie, MD) Non-anaplastic subtypes of T-cell lymphoma have poor outcomes and require new options. This study showed that adding brentuximab to conventional combination chemotherapy was tolerable and effective in patients with non-anaplastic CD30-positive peripheral T-cell lymphoma.
• Machine learning useful for stratifying lymphoma patients. (Abstract #2395, Andre Goy, MD) Using machine learning and data on 380 patients with DLBCL with expression levels of 180 genes, researchers used machine learning to develop a model to reliably stratify patients with DLBCL treated with R-CHOP combination therapy into four survival subgroups. The model can be used to identify which patients may not respond well to R-CHOP—a standard DLBCL treatment—and instead be considered for other therapies or clinical trials.
• Lymphoma/CLL adversely affects COVID-19 outcomes. (Abstract #184, Lori Leslie, MD) A study of electronic medical record data on 500 patients with lymphoma, chronic lymphocytic leukemia (CLL), or other lymphoid cancers who tested positive for SARS-CoV-2 showed that those with aggressive non-Hodgkin lymphoma and CLL and patients who had received recent cytotoxic chemotherapy or anti-CD20 antibody treatment (such as rituximab) may be at risk for poor COVID-19 outcomes. JTCC researchers are now working with investigators in the Center for Discovery and Innovation to study T-cell immunity in people with cancer.
• Other studies focused on adding ublituximab and umbralisib to ibrutinib in people with CLL (Abstract #395, Lori Leslie, MD) and assessing cerdulatinib as monotherapy for patients with relapsed/refractory peripheral T-cell lymphoma (Abstract #622, Tatayana Feldman, MD).

Leukemia Research

• Oral therapy for low-risk myelodysplastic syndrome (MDS) (Abstract #66, James McCloskey, MD) People with MDS are at risk for developing acute leukemia. Those with low-risk MDS may receive supportive care for low blood counts. Patients with high-risk MDS have received inconvenient injections with drugs such as azacitidine and decitabine. This study showed that oral decitabine and cedazuridine was pharmacokinetically equivalent to intravenous decitabine; in patients with low-risk MDS, the oral treatment was well tolerated with prolonged treatment and may be useful for preventing the progression of this disease to leukemia.
• Effectiveness of adding venetoclax to gilteritinib effective for FLT3-mutated acute leukemia (Abstract #691, James McCloskey, MD) Acute myeloid leukemia (AML) with FLT3 mutations initially responds to FLT3 inhibitors but frequently becomes resistant to these drugs. This study showed that giving venetoclax (a BCL2 inhibitor) with the FLT3 inhibitor gilteritinib was very effective, clearing the FLT3 mutation in most patients, and was associated with longer overall survival—even in patients with high-risk subtypes.
• Liquid biopsy for detecting molecular abnormalities in AML (Abstract #3463, Jamie Koprivnikar, MD, James McCloskey, MD, and others) This study assessed next-generation sequencing (NGS) to detect molecular abnormalities in AML using liquid biopsies. The data show that this approach is reliable for detecting structural chromosomal abnormalities in myeloid neoplasms. It could potentially replace the need for conventional cytogenetic testing, be much more convenient (replacing bone marrow biopsies for materials), and be more cost-effective.

Bone Marrow Transplantation Research

• Next-generation sequencing and liquid biopsy valuable for detecting early relapse after stem cell transplantation. (Abstract #1828, Scott Rowley, MD, Michele Donato, MD, Maher Albitar, MD, and others) Cell-free DNA was isolated from the peripheral blood post-allogeneic transplant in patients treated for AML, acute lymphocytic leukemia, chronic myelogenous leukemia, chronic myelomonocytic leukemia, MDS, MM, and lymphoma. Researchers showed that NGS and liquid biopsy are useful for detecting residual disease. The data suggest that this approach, which examines cancer DNA in peripheral blood rather than a sample from a bone marrow biopsy, may be effective for detecting and managing minimal residual disease (MRD)—the next frontier in oncology—enabling doctors to modify therapy to achieve MRD negative status or, during transplantation, to adjust immunosuppressors or use additional T cells to prevent relapse.
• Use of NGS and machine learning after transplant to predict graft-vs-host disease (GVHD) (Abstract #2892, Scott Rowley, MD, Michele Donato, MD, Maher Albitar, MD, and others) Using NGS RNA sequencing plus a machine learning approach, researchers looked at over 1,400 genes in 46 patients who had an allogeneic bone marrow transplant and developed a model based on 7 genes to predict acute GVHD, one of the most significant complications of receiving a transplant from a bone marrow donor. There are currently no valid ways to predict acute GVHD and intervene early until patients become symptomatic. The ability to identify molecular markers of this complication while patients are asymptomatic may allow for early intervention to prevent GVHD.

Sickle Cell Disease Research

• Sustained quality of life in patients receiving gene therapy for sickle cell disease (Abstract #7, Stacey Rifkin-Zenenberg, DO, Hackensack University Medical Center) LentiGlobin gene therapy (bb1111) has been under study in a clinical trial as a one-time treatment and cure for sickle cell disease. This study presented long-term quality of life data for one group in the study, demonstrating an improvement in hematologic parameters and complete resolution of veno-occlusive events and related pain as well as sustained and clinically meaningful improvement in quality of life 6 and 24 months post-treatment. Even patients with the worst baseline quality of life scores experienced a benefit. LentiGlobin is the first gene therapy for sickle cell disease and the results of this study are very promising, with the potential to change patient outcomes for this chronic debilitating disease.

The full set of ASH data presentations by JTCC researchers is as follows: 

For more information about the 63rd ASH Annual Meeting and Exposition or the research being presented, please visit: hematology.org/meetings/annual-meeting.