At the annual meeting of the American Society of Clinical Oncology, results were presented from a phase 1/2 trial in which patients with relapsed or refractory CD19+ B-cell malignancies were treated with CD19 CAR-T cells.
Cancer immunotherapy research has seen tremendous progress since the first checkpoint inhibitor, ipilimumab was approved in 2011. While combination immunotherapies are now being developed, they have their limitations because not all patients respond to the checkpoint inhibitors. Additionally, the absence of predictive biomarkers places limitations with respect to choosing positive responders for trial enrollment.
Chimeric antigen receptor T cells (CAR-T cells) are T cells genetically engineered to express a chimeric receptor on their cell surface. These cells are derived from the patient and then modified in vitro, before being reintroduced in the patient.1 This kind of immunotherapy has been gaining a lot of ground in clinical trials.
At the annual meeting of the American Society of Clinical Oncology, Cameron John Turtle, MBBS, PhD, Fred Hutchinson Cancer Research Center, presented results from a phase 1/2 trial in which patients with relapsed or refractory CD19+ B-cell malignancies received CD19 CAR-T cells. Rate of durable complete response in acute lymphocytic leukemia (ALL), non-Hodgkin lymphoma (NHL), and chronic lymphocytic leukemia (CLL), following immunotherapy with optimized lymphodepletion, was evaluated.
Thirty six patients with ALL were included in the trial, 33 of whom received products formulated in the defined composition; 26 were treated in an outpatient facility. Patients with ALL, Turtle said, had a high rate of minimal residual disease—negative complete response (CR), which was assessed using multiple techniques:
Turtle listed the 2 key observations for the patients with ALL:
Kaplan-Meier survival plots showed that over time, including fludarabine improved both disease-free and overall survival (OS) in patients with ALL.
Similarly, in patients diagnosed with NHL, the objective response rate (ORR) and CR was much improved following inclusion of fludarabine in the regimen. A high response rate in high-risk CLL patients was observed. In NHL, the ORR for patients treated with cyclophosphamide/lymphodepletion and fludarabine, was 84%. Additionally, CAR-T cell expansion and persistence, and OS and progression-free survival were better in patients whose regimen included fludarabine.
With respect to toxicity, Turtle said that overall the treatment is manageable. A majority of patients with ALL had very mild cytokine release syndrome (CRS); 90% with NHL had mild CRS, but did not require admission to the intensive care unit. Similarly, a majority of patients with CLL had mild CRS. The highest rate of neurotoxicity was observed in patients with ALL (39%), followed by CLL (23%), and least in NHL (20%).
Turtle concluded that adoptive therapy with CD19 CAR-T cells of defined subset composition results in durable CR in a high fraction of patients with relapsed/refractory ALL, NHL, and CLL. Optimizing the dosing regimen, he said, improved clinical outcomes in patients with ALL and NHL.
Expert Feedback
David L. Porter, MD, Lymphoma Program, Abramson Cancer Center, University of Pennsylvania, provided comments on the study presented by Turtle.
Porter explained that targeted cellular immunotherapy has the potential to overcome many limitations of conventional chemotherapy and other immunotherapy. CAR-T cells can be a perfect blend of antibody therapy, cellular therapy, and vaccine therapy, he said.
Porter was quite impressed by the data presented by Turtle, especially in patients with relapsed and refractory ALL. He added that, “Relapse after CR in CLL is unusual, and we expect the current CR rate of 25% to 45% will be sustained.”
There remain several unknowns with CAR-T cells, according to Porter.
Another limitation of this treatment, for both CLL and NHL, is the low CR rate of 25% to 50%. “How can this response rate be boosted?” asked Porter. To overcome some of these issues, Porter recommended developing a third-party donor of universal CAR-T cells.
EBO
In the future, Porter sees tremendous potential in tapping the synergism between CAR-T cells and checkpoint inhibitors. “Checkpoint activity may reduce CAR-T cell response, so it’s logical to combine the 2,” he concluded.
Reference
Low-Volume Hospitals Had Higher Reoperation Rate, Postoperative Complications in CRC
April 18th 2024Patients opting for elective colorectal surgery to address colorectal cancer (CRC) could have different rates of reoperation and postoperative complications based on the size of the hospital.
Read More
Prices for care at hospital trauma centers vary across hospitals; drug shortages reached a record high during the first quarter of 2024; although 3 of the biggest makers of asthma inhalers pledged to cap out-of-pocket costs for some US patients at $35, these do not apply to daily inhalers used by the youngest kids with asthma.
Read More
Oncology Onward: A Conversation With Penn Medicine's Dr Justin Bekelman
December 19th 2023Justin Bekelman, MD, director of the Penn Center for Cancer Care Innovation, sat with our hosts Emeline Aviki, MD, MBA, and Stephen Schleicher, MD, MBA, for our final episode of 2023 to discuss the importance of collaboration between academic medicine and community oncology and testing innovative cancer care delivery in these settings.
Listen
Study Links COVID-19 Pandemic to Rise in Neoadjuvant Chemotherapy for Ovarian Cancer in US
April 17th 2024There was greater use of neoadjuvant chemotherapy among US patients with ovarian cancer (OC) during the COVID-19 pandemic to reduce potential COVID-19 exposure and cancer treatment-related complications.
Read More