CancerConnect News: The 2017 annual meeting of the American Society of Hematology (ASH), held in Atlanta, Georgia included many presentations capturing the results of CAR T cell therapy in different types of blood cancers.
Chimeric antigen receptor (CAR) T-cell therapy is a new type of treatment that utilizes a patient’s own T-cells (a type of immune cell) to fight certain types of blood cancers. The T-cells are removed from the patient and engineered to recognize specific proteins found on the surface of cancer cells. The T-cells are then infused back into the patient to fight the cancer in their body.
Two agents used in the engineering process of T-cells have already been approved by the United States Food and Drug Administration (FDA) for the treatment of specific types of leukemia and lymphoma. Researchers are continuing to evaluate and improve upon existing CAR T-cell agents, as well as explore the options of their use in other cancers.
There are several types of non-Hodgkin’s lymphoma (NHL), which are cancers that affect different immune cells in different ways.
Diffuse large B-cell lymphoma (DLBCL) is the most common form of NHL, comprising approximately one-third of all NHL. One of the two CAR T cell therapies approved by the FDA, Kymria ™ (tisagenlecleucal), is approved for the treatment of a type of leukemia; however, it is being evaluated for treatment of DLBCL that has stopped responding to prior therapies. Tisagenlecleucal is an important component in engineering the T cells to recognize and bind to the CD-19 antigen, a protein that is found on B cells – which are the cancerous cells in DLBCL.
The current trial evaluating the effectiveness of tisagenlecleucal in DLBCL is referred to as the JULIET trial, in which updated results were presented at the 2017 ASH meeting.2
The JULIET trial included 81 patients with DLBCL whose cancer had stopped responding to standard therapy. Patients had received at least 2 prior therapies, and had either not responded to a stem cell transplant or were ineligible to receive one. In the trial, they were treated with a single infusion of CAR T cell therapy, which included tisagenlecleucel. The results presented were from patients who had at least 6 months follow-up from treatment with CAR T cell therapy.
- Overall anti-cancer responses occurred in 37% of patients
- Complete disappearance of cancer (complete response) was achieved in 30% of patients, and partial disappearance of cancer (partial response) was achieved in 7% of patients.
- Patients who achieved a complete response at 3 months remained cancer-free at 6 months and beyond
- The median time of anti-cancer responses and survival has not yet been reached among patients who responded to CAR T cell therapy; these patients have not received any additional therapy beyond the single infusion of CAR T cells.
- Side effects typically occurred directly after infusion, with no treatment-related deaths reported.
Of importance, researchers were able to freeze a patient’s CAR T cells without altering their effectiveness, which were infused when the patient’s physician felt it was optimal timing.
An additional clinical trial from the 2017 ASH meeting including results from CAR T cell therapy being used in NHL were updated results from the ZUMA-1 trial.3 The trial included the agent Yescart™ (axicabtagene ciloleucel, or axi-cel) which is already approved for the treatment of DLBCL, and also targets the CD-9 antigen.
The trial included108 patients with fast-growing DLBCL, or other aggressive B-cell NHLs, that had stopped responding to prior therapies. Patients were treated with a single infusion of CAR T cell therapy.
- One year following CAR T cell therapy, 40% of patients have no evidence of cancer
- Nearly 60% of patients are still alive after one year following treatment
- No new concerns regarding side effects were noted from the additional follow-up
The researchers concluded that a single infusion of CAR T cell therapy provides long-term responses among patients with aggressive DLBCL and other B-cell NHL that has stopped responding to standard therapies. They suggest that patients who maintain anti-cancer responses at 6 months following treatment tend to continue to respond long-term. The study also explored variables associated with long-term responses, including evidence of the protein, PD-L1 after treatment.
A clinical trial directly CAR T cell therapy to the standard stem cell transplant among patients whose NHL has stopped responding to prior therapy will be initiated shortly to further clarify the role of CAR T cell therapy in this group of patients.
Multiple myeloma is a type of cancer that starts in a patient’s plasma cells, which are a type of immune cell. Approximately 30,000 individuals in the United States will be diagnosed with multiple myeloma in 2017. The majority of patients who experience a progression of their myeloma following prior therapies have historically been considered incurable. However, as novel agents are making their way through the approval process, and research continues to uncover a greater understanding of this disease, patients with multiple myeloma continue to survival longer than in the past.
Researchers from the United States recently updated results from a continued study including multiple National Cancer Institute-based centers in the U.S.1 The trial included 21 patients with a median age of 58 years, who had received a median of 7 prior therapies, including stem cell transplants.
Just one infusion of an investigational CAR T-cell therapy provided high anti-cancer response rates among patients with multiple myeloma who received a multiple prior therapies. Importantly, higher doses of CAR T-cells provided greater responses than lower doses.
Patients were treated with CAR T-cells that were engineered to target the BCMA antigens (protein complexes) on cancer cells. These updated results were captured at 40 weeks (approximately 10 months) following the CAR T-cell treatment. Eighteen patients received higher doses of CAR T cells, while 3 patients received lower doses.
- Overall, 86% of patients achieved an anti-cancer response
- Among the 18 patients that received higher doses of CAR T cells, 94% achieved an anti-cancer response rate. Ten of these patients achieved a complete disappearance of their cancer.
- At 9 months following CAR T-cell therapy, over half (56%) of the patients had no evidence of their cancer.
- Anti-cancer responses appeared to improve over time among those who received the higher doses, indicating that data retrieval must be long-term to determine effectiveness of treatment.
- At 10 months following CAR T-cell therapy among these 18 patients, the median duration of survival has not yet been reached; however, 4 of these patients have experienced a progression of their disease.
- The 3 patients who were treated with lower doses of CAR T-cells experienced disease progression.
- Side effects were reported to be manageable.
The researchers concluded that these results add to the promise of CAR T-cell therapy in blood cancers, particularly since these patients had received extensive prior therapies, and achieved anti-cancer responses with just one infusion of CAR T cell therapy. Furthermore, greater understanding into improving outcomes, such as higher doses of CAR T-cells, is important as these new types of therapies are taking over historic standards as a way to treat cancers.
Overall, promising results from CAR T cell therapy continue to emerge for the treatment of different types of blood cancers, including multiple myeloma and NHL. Further research is ongoing to improve upon these outcomes, and expand the effectiveness of CAR T cell therapy to include more types of cancers.
- Berdeja, J., Lin, Y., Raje, N., Munshi, N., Siegel, D., Liedtke, M., Jagannath, S….Kochenderfer, J. (2017, December). Durable clinical responses in heavily pretreated patients with relapsed/refractory multiple myeloma: updated results from a multicenter study of bb2121 anti-bcma CAR T cell therapy. Presented at the 59th annual meeting and exposition of the American Society of Hematology. Atlanta, GA. Retrieved from ash.confex.com/ash/2017/webprogram/Paper107984.html
- Schuster, Bishop, Tam, et al. Primary analysis of Juliet: A global, pivotal, phase 2 trial of CTL019 in adult patients with relapsed or refractory diffuse large B-cell lymphoma. Proceedings from the 59th annual meeting and exhibition of the American Society of Hematology; Atlanta, GA; December 9-12, 2017; Abstract #577. Retrieved from ash.confex.com/ash/2017/webprogram/Paper105399.html
- Neelapu, Locke, Bartlett, et al. Long-term follow-up ZUMA-1: A pivotal trial of axicabtagene ciloleucel (axi-cel) in patients with refractory aggressive non-hodgkin lymphoma (NHL). Proceedings from the 59thannual meeting and exhibition of the American Society of Hematology; Atlanta, GA; December 9-12, 2017; Abstract #578. Retrieved from ash.confex.com/ash/2017/webprogram/Paper99983.html