Dec 2020: The University of Texas MD Anderson Cancer Center researchers discovered that axi-cel, an autologous anti-CD19 chimeric antigen receptor (CAR) T cell therapy, is a safe and effective first-line therapy for patients with high-risk large B-cell lymphoma (LBCL), a group in desperate need of new and effective treatments.
These findings were presented at the American Society of Hematology’s virtual 2020 Annual Meeting.
Traditionally, around half of patients with high-risk LBCL, a subgroup of the disease in which patients have double- or triple-hit lymphoma or additional clinical risk factors identified by the International Prognostic Index (IPI), have not achieved long-term disease remission with standard treatment approaches such as chemoimmunotherapy.
This trial represents a step toward making CAR T cell therapy a first-line treatment option for patients with aggressive B-cell lymphoma,” said Sattva S. Neelapu, M.D., professor of Lymphoma and Myeloma. At the moment, patients with newly diagnosed aggressive B-cell lymphoma get chemotherapy for about six months. CAR T cell therapy, if successful, may make it a one-time infusion with treatment completed in one month.
Based on the key research ZUMA-1, Axi-cel is presently licenced for the treatment of people with relapsed or refractory LBCL who have already had two or more lines of systemic treatments. The ZUMA-12 trial is a Phase 2 open-label, single-arm, multicenter trial that builds on the findings of the ZUMA-1 trial to assess the use of axi-cel as first-line therapy for patients with high-risk LBCL.
According to the ZUMA-12 interim study, 85 percent of patients treated with axi-cel had an overall response, and 74% had a complete response. After a median follow-up of 9.3 months, 70% of the patients recruited exhibited a continuing response at the data cutoff.
White blood cell count reduction, encephalopathy, anaemia, and cytokine release syndrome were the most common side effects linked with axi-cel treatment. By the time the data was analysed, all adverse events had been resolved.
Furthermore, when compared to when the immunotherapy products were generated from patients who had already received several lines of chemotherapy, the peak level of CAR T cells present in the blood, as well as the median CAR T cell expansion, were higher in this trial of first-line CAR T cell therapy.
“This T cell fitness could be linked to greater therapeutic effectiveness, resulting in better patient outcomes,” Neelapu added.
Following the excellent interim results of ZUMA-12, the researchers plan to continue following up with the patients to ensure that their reactions to the medication are long-lasting.
“A randomised clinical trial would be required to definitely demonstrate that CAR T cell therapy is superior to existing standard of care with chemoimmunotherapy in these high-risk patients if the responses are persistent after prolonged follow-up,” Neelapu said. It also begs the question of whether CAR T cell treatment should be tested in intermediate-risk patients with big B-cell lymphoma.
Dr. Nishant Mittal is a highly accomplished researcher with over 13 years of experience in the fields of cardiovascular biology and cancer research. His career is marked by significant contributions to stem cell biology, developmental biology, and innovative research techniques.
Research Highlights
Dr. Mittal's research has focused on several key areas:
1) Cardiovascular Development and Regeneration: He studied coronary vessel development and regeneration using zebrafish models1.
2) Cancer Biology: At Dartmouth College, he developed zebrafish models for studying tumor heterogeneity and clonal evolution in pancreatic cancer.
3) Developmental Biology: His doctoral work at Keio University involved identifying and characterizing medaka fish mutants with cardiovascular defects.
4) Stem Cell Research: He investigated the effects of folic acid on mouse embryonic stem cells and worked on cryopreservation techniques for hematopoietic stem cells.
Publications and Presentations
Dr. Mittal has authored several peer-reviewed publications in reputable journals such as Scientific Reports, Cardiovascular Research, and Disease Models & Mechanisms1. He has also presented his research at numerous international conferences, including the Stanford-Weill Cornell Cardiovascular Research Symposium and the Weinstein Cardiovascular Development Conference.
In summary, Dr. Nishant Mittal is a dedicated and accomplished researcher with a strong track record in cardiovascular and cancer biology, demonstrating expertise in various model systems and a commitment to advancing scientific knowledge through innovative research approaches.
