Car T-cell immunotherapy has shown great promise in non-Hodgkin’s lymphoma patients, according to data from a multicenter Phase 1/2 trial, presented at the 58th American Society of Hematology (ASH) Annual Meeting and Exposition Dec. 3-6 in San Diego.
The study, “Kte-C19 (anti-CD19 CAR T Cells) Induces Complete Remissions in Patients with Refractory Diffuse Large B-Cell Lymphoma (DLBCL): Results from the Pivotal Phase 2 Zuma-1,” presented by Dr. Sattva S. Neelapu, shows that nearly half of patients treated with the CAR T-cell therapy KTE-C19 achieved a complete response, which highly exceeds the complete response rate obtained with current therapies for refractory non-Hodgkin’s lymphoma.
Patients with non-Hodgkin’s lymphoma who do not respond to chemotherapy or whose cancer returns after an autologous stem cell transplant often face a very poor prognosis, and only about 8 percent of patients achieve complete responses with current therapies.
“Patients with aggressive non-Hodgkin lymphoma have a major unmet need in terms of available therapies that can induce long-term remission, and there really has been no new treatment for these patients for over 20 years,” Neelapu, of The University of Texas MD Anderson Cancer Center in Houston, said in a news release. “KTE-C19 could potentially be the solution to that need, and the hope is that this treatment option could be curative for some of these patients.”
KTE-C19, Kite Pharma‘s lead candidate, is a CAR (chimeric antigen receptor) T-cell therapy that removes the patient’s own T-cells and genetically engineers them to express a receptor that recognizes the CD19 protein found at the surface of most lymphoma cells. Then, engineered cells are expanded in the lab and reinfused back into the patient’s blood stream.
The Phase 1/2 ZUMA-1 study (NCT02348216) is an open-label, single-arm trial designed to assess the safety and effectiveness of KTE-C19 in patients with refractory, aggressive non-Hodgkin’s lymphoma, including refractory diffuse large B-cell lymphoma (DLBCL), primary mediastinal B-cell lymphoma (PMBCL), and transformed follicular lymphoma (TFL).
In the first Phase of ZUMA-1, conducted at four institutions, researchers found that 43 percent of patients had ongoing complete responses at 12 months, which largely surpassed the responses seen with standard of care therapies.
To test the real-world feasibility of KTE-C19, the second part of the trial expanded to include 22 institutions, most of which had never worked with CAR T-cell therapies.
“Efficacy often tends to be lower when you apply a new treatment at multiple centers,” Neelapu said. “It was very gratifying to see that efficacy and side effects are similar to what was observed in previous single-institution studies.”
Indeed, data from the second Phase of ZUMA-1, including 51 patients with DLBCL, has revealed that 76 percent of patients responded to the therapy, which included 47 percent complete responses and 29 percent partial responses. Most patients responded within the first month.
Similar to previous studies, some patients who first responded to the therapy eventually relapsed. But three months after the beginning of the treatment, 39 percent of patients still exhibited responses, including 33 percent complete responses and 6 percent partial responses.
Among the DLBCL cohort, which included 73 patients, serious neurological events were seen in 25 percent of participants, and grade 3 or higher cytokine release syndrome, which induced fever, low blood pressure, and shortness of breath, was observed in 14 percent of patients. One patient died due to over-activation of the immune system, as reported by the researchers.
“We now have guidelines on how to recognize and grade these side effects and how to manage the symptoms, and we were able to implement those across multiple institutions with no prior experience with CAR T-cell therapy,” Neelapu said. “I think it has become much more manageable and safer now.”
In another oral presentation, titled “A Phase 2 Multicenter Trial of KTE-C19 (anti-CD19 CAR T Cells) in Patients With Chemorefractory Primary Mediastinal B-Cell Lymphoma (PMBCL) and Transformed Follicular Lymphoma (TFL): Interim Results From ZUMA-1,” researchers also reported the results of KTE-C19 in patients with refractory PMBCL and TFL, showing that 80 percent of these patients respond to the therapy, with 55 percent showing complete responses.
The researchers will now follow the patients in both cohorts of the ZUMA-1 trial for 15 years to address the long-term effects of this therapy.