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ORLANDO – KTE-X19, an anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, demonstrated unprecedented efficacy in the ZUMA-2 trial, according to an investigator involved in the study.
KTE-X19 produced a 93% overall response rate in patients with relapsed/refractory mantle cell lymphoma (MCL). This is the highest reported response rate in patients who have failed treatment with a Bruton’s tyrosine kinase (BTK) inhibitor, said Michael L. Wang, MD, of the University of Texas MD Anderson Cancer Center in Houston.
Dr. Wang presented results from ZUMA-2 at the annual meeting of the American Society of Hematology.
“Patients with relapsed/refractory MCL have very poor outcomes,” Dr. Wang noted. “In patients who progress after BTK inhibition therapy, the overall response rate is only between 25% and 42%, and the overall survival is only between 6 and 10 months. Few patients proceed to allogeneic transplantation.”
The phase 2 ZUMA-2 trial was designed to test KTE-X19 in these patients. KTE-X19 is an anti-CD19 CAR T-cell therapy containing a CD3-zeta T-cell activation domain and a CD28 signaling domain. KTE-X19 is distinct from axicabtagene ciloleucel (KTE-C19) because the manufacturing process for KTE-X19 removes circulating tumor cells.
The trial enrolled 74 patients, and 68 of them received KTE-X19. Manufacturing failed for three patients, two patients died of progressive disease before they could receive KTE-X19, and one patient was found to be ineligible for treatment.
The 68 patients had a median age of 65 years (range, 38-79 years), and 84% were men. A majority of patients (85%) had stage IV disease and classical (59%) or blastoid (25%) morphology. Most patients (69%) had a Ki-67 proliferation index of 50% or greater, and most (56%) were intermediate- or high-risk according to the Mantle Cell Lymphoma International Prognostic Index (MIPI).
Patients had received a median of three prior therapies (range, one to five). All had been treated with a BTK inhibitor, with 85% receiving ibrutinib, 24% receiving acalabrutinib, and 9% receiving both. Most patients (68%) were refractory to BTK inhibition, and 32% relapsed on or after BTK inhibitor therapy.
In this study, patients could receive bridging therapy to keep their disease stable while KTE-X19 was being manufactured. There were 25 patients who received bridging therapy, which consisted of ibrutinib (n = 14), acalabrutinib (n = 5), dexamethasone (n = 12), and/or methylprednisolone (n = 2). Six patients received both BTK inhibitors and steroids.
All patients received conditioning with fludarabine and cyclophosphamide, followed by a single infusion of KTE-X19 at 2x106.
Efficacy
Sixty patients were evaluable for efficacy, and the median follow-up was 12.3 months (range, 7.0-32.3 months).
The overall response rate was 93%, with 67% of patients achieving a complete response and 27% achieving a partial response. Three percent of patients had stable disease, and 3% had progressive disease.
“The overall response rate was consistent across key subgroups, without any statistical difference,” Dr. Wang said. “This includes Ki-67, MIPI, and prior use of either steroids or bridging therapy.”
The median time to response was 1.0 month, and the median time to complete response was 3.0 months. Responses deepened over time, with 35% of patients converting from a partial response to a complete response, and 5% converting from stable disease to complete response.
The median duration of response has not been reached. At last follow-up, 57% of all patients and 78% of complete responders were still in response.
The median progression-free and overall survival have not been reached. At 12 months, the progression-free survival rate was 61%, and the overall survival rate was 83%.
Safety
All 68 patients were evaluable for safety. The most common adverse events were pyrexia (94%), neutropenia (87%), thrombocytopenia (74%), anemia (68%), and hypotension (51%).
Grade 3/4 adverse events included pyrexia (13%), neutropenia (85%), thrombocytopenia (51%), anemia (50%), hypotension (22%), hypoxia (21%), hypophosphatemia (22%), fatigue (1%), and headache (1%).
There were two grade 5 treatment-related adverse events – organizing pneumonia on day 37 and staphylococcal bacteremia on day 134.
Cytokine release syndrome (CRS) occurred in 91% of patients, with 15% experiencing grade 3 or higher CRS. Patients were treated with tocilizumab or corticosteroids, and all CRS events resolved.
Neurologic adverse events occurred in 63% of patients, with grade 3 or higher events occurring in 31%. Neurologic events were treated with tocilizumab or corticosteroids, and 86% of neurologic events resolved.
This trial was sponsored by Kite, a Gilead company. Dr. Wang reported financial relationships with Kite and other companies.
SOURCE: Wang M et al. ASH 2019. Abstract 754.
ORLANDO – KTE-X19, an anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, demonstrated unprecedented efficacy in the ZUMA-2 trial, according to an investigator involved in the study.
KTE-X19 produced a 93% overall response rate in patients with relapsed/refractory mantle cell lymphoma (MCL). This is the highest reported response rate in patients who have failed treatment with a Bruton’s tyrosine kinase (BTK) inhibitor, said Michael L. Wang, MD, of the University of Texas MD Anderson Cancer Center in Houston.
Dr. Wang presented results from ZUMA-2 at the annual meeting of the American Society of Hematology.
“Patients with relapsed/refractory MCL have very poor outcomes,” Dr. Wang noted. “In patients who progress after BTK inhibition therapy, the overall response rate is only between 25% and 42%, and the overall survival is only between 6 and 10 months. Few patients proceed to allogeneic transplantation.”
The phase 2 ZUMA-2 trial was designed to test KTE-X19 in these patients. KTE-X19 is an anti-CD19 CAR T-cell therapy containing a CD3-zeta T-cell activation domain and a CD28 signaling domain. KTE-X19 is distinct from axicabtagene ciloleucel (KTE-C19) because the manufacturing process for KTE-X19 removes circulating tumor cells.
The trial enrolled 74 patients, and 68 of them received KTE-X19. Manufacturing failed for three patients, two patients died of progressive disease before they could receive KTE-X19, and one patient was found to be ineligible for treatment.
The 68 patients had a median age of 65 years (range, 38-79 years), and 84% were men. A majority of patients (85%) had stage IV disease and classical (59%) or blastoid (25%) morphology. Most patients (69%) had a Ki-67 proliferation index of 50% or greater, and most (56%) were intermediate- or high-risk according to the Mantle Cell Lymphoma International Prognostic Index (MIPI).
Patients had received a median of three prior therapies (range, one to five). All had been treated with a BTK inhibitor, with 85% receiving ibrutinib, 24% receiving acalabrutinib, and 9% receiving both. Most patients (68%) were refractory to BTK inhibition, and 32% relapsed on or after BTK inhibitor therapy.
In this study, patients could receive bridging therapy to keep their disease stable while KTE-X19 was being manufactured. There were 25 patients who received bridging therapy, which consisted of ibrutinib (n = 14), acalabrutinib (n = 5), dexamethasone (n = 12), and/or methylprednisolone (n = 2). Six patients received both BTK inhibitors and steroids.
All patients received conditioning with fludarabine and cyclophosphamide, followed by a single infusion of KTE-X19 at 2x106.
Efficacy
Sixty patients were evaluable for efficacy, and the median follow-up was 12.3 months (range, 7.0-32.3 months).
The overall response rate was 93%, with 67% of patients achieving a complete response and 27% achieving a partial response. Three percent of patients had stable disease, and 3% had progressive disease.
“The overall response rate was consistent across key subgroups, without any statistical difference,” Dr. Wang said. “This includes Ki-67, MIPI, and prior use of either steroids or bridging therapy.”
The median time to response was 1.0 month, and the median time to complete response was 3.0 months. Responses deepened over time, with 35% of patients converting from a partial response to a complete response, and 5% converting from stable disease to complete response.
The median duration of response has not been reached. At last follow-up, 57% of all patients and 78% of complete responders were still in response.
The median progression-free and overall survival have not been reached. At 12 months, the progression-free survival rate was 61%, and the overall survival rate was 83%.
Safety
All 68 patients were evaluable for safety. The most common adverse events were pyrexia (94%), neutropenia (87%), thrombocytopenia (74%), anemia (68%), and hypotension (51%).
Grade 3/4 adverse events included pyrexia (13%), neutropenia (85%), thrombocytopenia (51%), anemia (50%), hypotension (22%), hypoxia (21%), hypophosphatemia (22%), fatigue (1%), and headache (1%).
There were two grade 5 treatment-related adverse events – organizing pneumonia on day 37 and staphylococcal bacteremia on day 134.
Cytokine release syndrome (CRS) occurred in 91% of patients, with 15% experiencing grade 3 or higher CRS. Patients were treated with tocilizumab or corticosteroids, and all CRS events resolved.
Neurologic adverse events occurred in 63% of patients, with grade 3 or higher events occurring in 31%. Neurologic events were treated with tocilizumab or corticosteroids, and 86% of neurologic events resolved.
This trial was sponsored by Kite, a Gilead company. Dr. Wang reported financial relationships with Kite and other companies.
SOURCE: Wang M et al. ASH 2019. Abstract 754.
ORLANDO – KTE-X19, an anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, demonstrated unprecedented efficacy in the ZUMA-2 trial, according to an investigator involved in the study.
KTE-X19 produced a 93% overall response rate in patients with relapsed/refractory mantle cell lymphoma (MCL). This is the highest reported response rate in patients who have failed treatment with a Bruton’s tyrosine kinase (BTK) inhibitor, said Michael L. Wang, MD, of the University of Texas MD Anderson Cancer Center in Houston.
Dr. Wang presented results from ZUMA-2 at the annual meeting of the American Society of Hematology.
“Patients with relapsed/refractory MCL have very poor outcomes,” Dr. Wang noted. “In patients who progress after BTK inhibition therapy, the overall response rate is only between 25% and 42%, and the overall survival is only between 6 and 10 months. Few patients proceed to allogeneic transplantation.”
The phase 2 ZUMA-2 trial was designed to test KTE-X19 in these patients. KTE-X19 is an anti-CD19 CAR T-cell therapy containing a CD3-zeta T-cell activation domain and a CD28 signaling domain. KTE-X19 is distinct from axicabtagene ciloleucel (KTE-C19) because the manufacturing process for KTE-X19 removes circulating tumor cells.
The trial enrolled 74 patients, and 68 of them received KTE-X19. Manufacturing failed for three patients, two patients died of progressive disease before they could receive KTE-X19, and one patient was found to be ineligible for treatment.
The 68 patients had a median age of 65 years (range, 38-79 years), and 84% were men. A majority of patients (85%) had stage IV disease and classical (59%) or blastoid (25%) morphology. Most patients (69%) had a Ki-67 proliferation index of 50% or greater, and most (56%) were intermediate- or high-risk according to the Mantle Cell Lymphoma International Prognostic Index (MIPI).
Patients had received a median of three prior therapies (range, one to five). All had been treated with a BTK inhibitor, with 85% receiving ibrutinib, 24% receiving acalabrutinib, and 9% receiving both. Most patients (68%) were refractory to BTK inhibition, and 32% relapsed on or after BTK inhibitor therapy.
In this study, patients could receive bridging therapy to keep their disease stable while KTE-X19 was being manufactured. There were 25 patients who received bridging therapy, which consisted of ibrutinib (n = 14), acalabrutinib (n = 5), dexamethasone (n = 12), and/or methylprednisolone (n = 2). Six patients received both BTK inhibitors and steroids.
All patients received conditioning with fludarabine and cyclophosphamide, followed by a single infusion of KTE-X19 at 2x106.
Efficacy
Sixty patients were evaluable for efficacy, and the median follow-up was 12.3 months (range, 7.0-32.3 months).
The overall response rate was 93%, with 67% of patients achieving a complete response and 27% achieving a partial response. Three percent of patients had stable disease, and 3% had progressive disease.
“The overall response rate was consistent across key subgroups, without any statistical difference,” Dr. Wang said. “This includes Ki-67, MIPI, and prior use of either steroids or bridging therapy.”
The median time to response was 1.0 month, and the median time to complete response was 3.0 months. Responses deepened over time, with 35% of patients converting from a partial response to a complete response, and 5% converting from stable disease to complete response.
The median duration of response has not been reached. At last follow-up, 57% of all patients and 78% of complete responders were still in response.
The median progression-free and overall survival have not been reached. At 12 months, the progression-free survival rate was 61%, and the overall survival rate was 83%.
Safety
All 68 patients were evaluable for safety. The most common adverse events were pyrexia (94%), neutropenia (87%), thrombocytopenia (74%), anemia (68%), and hypotension (51%).
Grade 3/4 adverse events included pyrexia (13%), neutropenia (85%), thrombocytopenia (51%), anemia (50%), hypotension (22%), hypoxia (21%), hypophosphatemia (22%), fatigue (1%), and headache (1%).
There were two grade 5 treatment-related adverse events – organizing pneumonia on day 37 and staphylococcal bacteremia on day 134.
Cytokine release syndrome (CRS) occurred in 91% of patients, with 15% experiencing grade 3 or higher CRS. Patients were treated with tocilizumab or corticosteroids, and all CRS events resolved.
Neurologic adverse events occurred in 63% of patients, with grade 3 or higher events occurring in 31%. Neurologic events were treated with tocilizumab or corticosteroids, and 86% of neurologic events resolved.
This trial was sponsored by Kite, a Gilead company. Dr. Wang reported financial relationships with Kite and other companies.
SOURCE: Wang M et al. ASH 2019. Abstract 754.
REPORTING FROM ASH 2019