Hackensack Meridian John Theurer Cancer Center Researchers to Present Pivotal Investigations at Annual Meeting of the American Society of Hematology

Findings Have Potential to Change Standard of Care for Blood Cancers

Researchers from Hackensack Meridian John Theurer Cancer Center, a part of Georgetown Lombardi Comprehensive Cancer Center, are presenting the latest data from their investigations assessing new diagnostic and treatment approaches for hematologic malignancies — including lymphoma, leukemia, and multiple myeloma — at the 64th Annual Meeting of the American Society of Hematology, to be held virtually and live in New Orleans from December 10-13, 2022.

"While our cancer experts treat all types and stages of cancer, John Theurer Cancer Center is especially well known for our leadership in the management of people with blood cancers. We are proud to present so many studies at this year's meeting and demonstrate our commitment to improving outcomes and quality of life for people diagnosed with hematologic cancers," said Andre Goy, MD, MS, chairman and executive director of John Theurer Cancer Center.

The JTCC presentations address new therapies for lymphoma, leukemia, and multiple myeloma, as well as approaches to improving the effectiveness of treatments such as CAR T-cell therapy and bone marrow transplantation and novel diagnostics that use next-generation sequencing.

Non-Hodgkin and Hodgkin Lymphoma Research

• Real-world data used to optimize fludarabine dose before CAR T-cell therapy. (Abstract #657, Lori A. Leslie, MD) During CAR T-cell therapy, some of a patient's white blood cells are removed, modified in a lab to learn to recognize cancer cells, and returned to the patient to mount an immune response against cancer cells. Chemotherapy that includes fludarabine is given before CAR T-cell therapy to prepare the body to receive this immunotherapy and enhance its effectiveness. In this study, researchers from JTCC and Memorial Sloan Kettering Cancer Center collaborated on a model which applied real-world data to define the optimal dose of fludarabine for patients receiving axi-cel CAR T-cell therapy for aggressive B-cell non-Hodgkin lymphoma (NHL), achieving the highest overall survival rate, lowest rate of recurrence, and fewest side effects.
• Follow-up study confirms prior ZUMA-5 study data. (Abstract 4660, Lori A. Leslie, MD) A three-year phase 2 follow-up analysis in the ZUMA-5 study assessing axi-cel CAR T-cell therapy for recurrent and persistent indolent follicular lymphoma and marginal zone lymphoma (MZL) confirmed the durability of the two-year data, with high rates of overall response and complete response and no new side effects. Peak CAR T-cell levels were highest among those who continued to respond to treatment at the three-year mark. The results confirm the effectiveness of axi-cel in these patients.
• Brexu-cel CAR T-cell therapy may be most effective against mantle cell lymphoma when given early. (Abstract #4199, Andre Goy, MD) After three years of follow-up in the ZUMA-2 study, brexu-cel CAR T-cell therapy continued to be effective in 49% of patients with recurrent or persistent mantle cell lymphoma (MCL). Data on tumor burden, prior therapies, and overall health suggest the treatment may have the greatest benefit if given earlier in the course of the disease.
• Zilovertamab plus ibrutinib shows promising effectiveness. (Abstract #232, Lori A. Leslie, MD) A phase 1/2 study showed that combining zilovertamab (an inhibitor of the ROR1 protein) with ibrutinib (which blocks the BTK protein) achieved an overall response rate of 85% for a median duration of 34 months in patients with MCL, MZL, or chronic lymphocytic leukemia (CLL). Zilovertamab consists of an antibody linked with an anticancer drug; the antibody binds to the ROR1 protein and releases the chemotherapy drug, which enters and destroys the cancer cell. The study is ongoing and supports the promise of combining targeted therapies to achieve good outcomes against lymphoma with less toxicity.
• Real-world outcomes differ from clinical trial data for dual-drug lymphoma treatment. (Abstract #323, Lori A. Leslie, MD) A multicenter study assessing tafasitamab with lenalidomide for recurrent or persistent large B-cell lymphoma showed that patients receiving these drugs outside of the L-MIND clinical trial did not do as well as study participants, particularly if they had high-risk disease, more comorbidities, more prior regimens of treatment, and delays and dose-reductions in lenalidomide therapy. The findings may help physicians decide which patients may best benefit from this treatment combination.
• Epcoritamab with rituximab and lenalidomide could become new standard as initial follicular lymphoma treatment. (Abstract #611, Lori A. Leslie, MD) Epcoritamab is a bispecific antibody which helps engage T cells to fight cancer. In this phase 1/2 study, it was combined with rituximab and lenalidomide as initial therapy for people with follicular lymphoma. Early data show that 90% of patients responded to the treatment, including 69% who experienced a complete response (versus 49% for patients who received lenalidomide and rituximab alone), and with acceptable side effects. If confirmed in larger studies, this treatment could become a new standard as front-line therapy for follicular lymphoma.
• Brentuximab vedotin with immunotherapy and chemotherapy may transform initial treatment of Hodgkin lymphoma. (Abstracts #728 and 314, Tatyana Feldman, MD) For over 30 years, the standard treatment for Hodgkin lymphoma has been a combination of drugs abbreviated ABVD. Researchers are seeking treatments that involve less chemotherapy. In one study, they tailored a patient's medications to their disease status as determined by PET scanning, giving brentuximab vedotin and nivolumab immunotherapy after a shorter course of chemotherapy in patients with limited-stage Hodgkin disease and showing a 97% complete response rate after only three cycles of treatment. A second study reported that combining brentuximab vedotin and nivolumab with doxorubicin and dacarbazine chemotherapy achieved a 93% overall response rate and 83% complete response rate in patients with advanced Hodgkin lymphoma. While the results are early, the findings of both investigations could lead to a change in the initial treatment of early and advanced Hodgkin disease.

Multiple Myeloma Research

• Using precision medicine to tailor multiple myeloma treatment. (Abstract #1931, Noa Biran, MD)  Medicines targeting specific genetic abnormalities may help overcome the resistance patients with multiple myeloma develop to treatment. MyDRUG is a platform trial of patients with select genetic mutations. Researchers evaluated a backbone regimen of ixazomib, pomalidomide, and dexamethasone plus another agent based on next-generation sequencing of a patient's multiple myeloma cells — in this case, daratumumab. The overall response rate for patients with high-risk multiple myeloma who received these four medications was 92%, with manageable side effects. The study is ongoing but underscores the value of precision medicine for customizing cancer care.
• Gut health may influence outcome of stem cell transplantation. (Abstract #2112, Rena Feinman, PhD) Engraftment syndrome is an inflammatory complication often seen in patients with multiple myeloma receiving high-dose chemotherapy followed by autologous stem cell transplantation and causes symptoms such as diarrhea, fever, and skin rash. Investigators showed that a patient's microbiome influenced their chance of developing this complication, with people whose microbiomes were high in Enterococcus having an increased risk of engraftment syndrome. Microbiota-focused interventions have the potential to improve outcomes in patients undergoing autologous stem cell transplantation for multiple myeloma.
• Ide-cel CAR T-cell therapy is effective in people with high-risk multiple myeloma persisting after stem cell transplantation. (Abstract #3314, David Siegel, MD, PhD) Researchers showed that in people with high-risk multiple myeloma who have an inadequate response to autologous stem cell transplantation, ide-cel CAR T-cell therapy achieved an 87% overall response rate and 74% complete response, with fewer side effects. The findings suggest a role for ide-cel earlier in the course of the disease to promote deep, durable treatment responses.
• Nanoparticle therapy for multiple myeloma and lymphoma shows promise. (Abstract #2682, David Siegel, MD, PhD, Johannes Zakrzewski, MD) In a collaboration between JTCC and Hackensack Meridian Health Center for Discovery and Innovation, laboratory studies demonstrated the value of a nanotherapy called IT848, an inhibitor of a protein called nuclear factor kappa-beta, for slowing cancer cell growth and inducing cancer cell death. Nanoparticle therapy for cancer is considered a young field with much potential for delivering drugs directly and safely to cancer cells.

Leukemia Research

• V-MAST study shows value of combining CPX-351 with midostaurin for high-risk acute myeloid leukemia. (Abstract #1436, James McCloskey, MD) Acute myeloid leukemia (AML) that contains mutations in a gene called FLT3 is an aggressive cancer. CPX-351 is used to treat AML that has continued to grow despite treatment or has developed as a result of progressive myelodysplastic syndrome (MDS). In this study, researchers showed the value of giving CPX-351 with the chemotherapy agent midostaurin as initial treatment for FLT3-mutated AML, with 83% of patients achieving a complete response to the drug combination and acceptable side effects. The data are early but encouraging.
• TP-3654 is effective against myelofibrosis. (Abstract #240, James McCloskey, MD) Myelofibrosis is a scarring of the bone marrow that also causes an enlarged spleen and debilitating symptoms. TP-3654 is a drug that targets PIM-1, a protein that is very active in myelofibrosis cells. Preliminary data from a small phase 1/2 study showed that TP-3654 resulted in a reduction in spleen size and improvement of symptoms in people with myelofibrosis for whom other drugs called JAK inhibitors were not an effective treatment option. The researchers concluded that TP-3654 should continue to be assessed, particularly in combination with JAK inhibitors.

Precision Medicine and Diagnostics

• Machine learning with DNA and RNA profiling useful for predicting which AML/MDS patients will respond to venetoclax. (Abstract #2789, Maher Albitar, MD, and James McCloskey, MD) Venetoclax is used to treat AML and MDS as an alternative to standard induction therapy, but little is known about which patients stand to benefit most. In this study, investigators applied bone marrow DNA and RNA profiling to a machine learning algorithm to predict which patients with AML/MDS were most likely to respond to venetoclax given with either azacitidine or decitabine. They were able to predict patients who achieved a complete response with a sensitivity of 94% and a specificity of 93%. They concluded that bone marrow expression profiling, when used with machine learning, may be a valuable and practical approach for selecting AML/MDS patients who are most likely to respond to venetoclax-based treatment. The model is an example of the way precision medicine can be used to predict patient outcomes
• Next-generation sequencing with machine learning can predict bone marrow complication. (Abstract #2076, Maher Albitar, MD) Graft-versus-host disease (GVHD) is a serious complication of allogeneic (donated) stem cell transplantation, but there is no way to predict a patient's risk. Most prior studies have focused on the role of donor cells, but in this study, researchers looked at the microenvironment of the transplant recipient. Using targeted RNA next-generation sequencing applied to bone marrow samples taken from the recipient before and after the transplant, they developed a machine learning algorithm that was highly sensitive for predicting GVHD risk and overall survival. The tool may enable doctors to intervene with treatments to prevent or treat GVHD sooner.
• RNA-based liquid biopsy effective for diagnosing lymphoid cancers. (Abstract #3488, Maher Albitar, MD, Andre Goy, MD) Cell-free DNA has formed the basis of "liquid biopsy," in which fragments of tumor DNA can be detected in the bloodstream early in the course of disease. In this study, investigators evaluated a liquid biopsy test based on cell-free RNA in 120 patients with different types of lymphoid malignancies. They found it was highly accurate not only for diagnosing and classifying cancers such as MCL, CLL, follicular lymphoma, and diffuse large B-cell lymphoma, but also for determining prognosis and the best therapies for each patient. This method could be extremely helpful for validating liquid biopsies to diagnosis early blood cancers, refine treatment decision-making, and monitoring patient outcomes.