Triple-Blast Meds Trial Takes Aim at Lymphoma
Article Summary
- Dr. Jay Spiegel has received a $200,000 V Foundation early-career grant to combine CAR T immunotherapy with two promising anti-cancer drugs to treat lymphoma.
- The study will examine the ability of mosunetuzumab and polatuzumab to boost the power of CAR T-cell therapy.
- The trial will involve 40 patients and span three-and-one-half months.
When it comes to treating lymphoma, you can never have too much of a good thing.
That’s the underlying philosophy behind an ongoing clinical trial for which Jay Spiegel, M.D., received a $200,000, two-year grant from the V Foundation.
Dr. Spiegel is a cancer hematologist and transplant and cellular therapy physician in the Division of Transplant and Cellular Therapy at Sylvester Comprehensive Cancer Center, part of the University of Miami Miller School of Medicine.
The early-career award will allow Dr. Spiegel, an assistant professor of hematology at the Miller School, to tackle aggressive B-cell lymphoma by blending CAR T immunotherapy with two promising new drugs, mosunetuzumab and polatuzumab. The combined therapies increase the chances for better patient outcomes than the three interventions on their own.
Dr. Spiegel’s approach may open the door to a new way to treat the disease.
“I entered medicine to make a meaningful difference in people’s lives,” he said. “This grant will help me to do just that. I am very grateful to the V Foundation for its generosity.”
The Most Common Lymphoma
B-cell lymphoma is the most common type of lymphoma in the United States, comprising about 85% of all cases. It starts in the lymphocytes— white blood cells crucial to the lymphatic system. Two key lymphocytes, B cells and T cells, play significant roles in maintaining health. B cells produce antibodies that attack dangerous bacteria and viruses. T cells, the bedrock of CAR T-cell therapy, strike against cells that have been commandeered by toxins or are cancerous.
CAR T-cell therapy is a form of precision medicine primarily used for blood cancers, including B-cell lymphoma. The patient’s T cells are temporarily removed from the body and genetically engineered to fortify their destructive capabilities. Returned to the body, the cells track and destroy tumor cells while bypassing healthy tissue.
“Cancer immunotherapy such as CAR T treatment has been one of the important advances in addressing blood cancer in the past generation,” said Dr. Spiegel. “It has made especially strong gains over the last five years. However, despite CAR T leading to growing rates of remission, only about 40 percent of patients are formally cured.”
Major obstacles include an overabundance of tumor cells and, in about half of the cases, cancer “learns” to hide the target gene, CD19, from the T cells.
An Increase in CAR T-cell Therapy Potency
In Dr. Spiegel’s trial, the hope is that adding mosunetuzumab and polatuzumab will boost the power of CAR T-cell therapy. The two drugs may be able to outfox the cancer by bypassing the “hidden” CD19 gene and placing two other lymphoma genes, CD20 and CD79b, in their crosshairs.
Dr. Spiegel targeted mosunetuzumab and polatuzumab because they attack lymphoma in multiple ways. Additionally, both appear biologically capable of bolstering CAR T-cell therapy. Historically, mosunetuzumab and polatuzumab have been more successful when paired together. Mosunetuzumab has already been shown to work synergistically with CAR T-cell therapy pre-clinically.
“In this trial we will be taking the synergy of two drugs that already mesh well with each other and adding it to the synergy created by mosunetuzumab working in tandem with CAR T,” he said. “That means, in essence, we will be adding synergy upon synergy in the hope of achieving even more compelling results.”
The Clinical Trial Process
Dr. Spiegel’s trial is a three-phase process involving 40 patients and spanning three-and-one-half months. Mosunetuzumab and polatuzumab will be administered prior to the introduction of CAR T-cell therapy on its own. The therapy concludes with a course of mosunetuzumab and polatuzumab together.
“Combining three anti-cancer interventions together is very intense,” said Dr. Spiegel. “It’s a maximalist approach. We need to assess its feasibility as well as its efficacy.”
CAR T-cell therapy has a high risk of infection. Dr. Spiegel will monitor patients’ immune systems by tracking T-cell counts and profiles and assessing the recovery of normal B cells. Adjustments will be made as needed.
“Further down the road,” he said, “we will need to be mindful of the generalizability of our results because the characteristics of patients outside the clinical trial setting may not match the characteristics of those who participated in the research.”
But for now, the upcoming study represents a promising opportunity to push the anti-cancer frontier forward.
Tags: 2024 V Foundation, CAR T cells, diffuse large B cell lymphoma, Dr. Jay Spiegel, immunotherapy, lymphoma, Sylvester Comprehensive Cancer Center, V Foundation