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When given after low-dose chemotherapy, an anti-CD19 chimeric antigen receptor (CAR) T-cell therapy can produce durable complete responses (CRs) in patients with relapsed/refractory non-Hodgkin lymphoma (NHL), according to research published in the Journal of Clinical Oncology.
In this phase 1 study, the overall response rate was 73%, and 50% of patients had an ongoing CR at last follow-up.
Fifty-five percent of patients experienced grade 3/4 neurologic toxicities, though these events eventually resolved.
This research was conducted under a cooperative research and development agreement between the National Cancer Institute and Kite Pharma, Inc.
Kite is developing the CAR T-cell therapy axicabtagene ciloleucel (formerly known as KTE-C19), and the therapy tested in this trial has the same CAR construct as axicabtagene ciloleucel.
Results from this study (NCT00924326) were previously published in the Journal of Clinical Oncology in 2014.
The current report included 22 patients with relapsed/refractory NHL. Seventeen patients had diffuse large B-cell lymphoma (DLBCL), 2 had primary mediastinal B-cell lymphoma (PMBCL), 2 had follicular lymphoma (FL), and 1 had mantle cell lymphoma (MCL).
Patients received a single dose of CAR T cells 2 days after a low-dose chemotherapy conditioning regimen consisting of cyclophosphamide and fludarabine.
Response
The overall response rate was 73% (16/22), with a CR rate of 55% (n=12) and a partial response (PR) rate of 18% (n=4).
Among patients with DLBCL, there were 9 CRs, 4 PRs, 1 patient with stable disease, and 3 patients with progressive disease.
Both FL patients achieved a CR, as did the patient with MCL. One patient with PMBCL had stable disease, and the other progressed.
Eleven of the 12 CRs are ongoing, with durations ranging from more than 7 months to more than 24 months. The median duration of CR is 12.5 months.
The researchers found that serum IL-15 levels and CAR T-cell expansion correlated with treatment response (CR or PR).
The median peak blood CAR+ cell level was 98/μL in patients who achieved a response and 15/μL in those who did not (P=0.027).
High serum IL-15 levels were significantly associated with high peak blood CAR+ cell levels (P=0.001) and response (P<0.001).
Toxicity
Fifty-five percent of patients had grade 3 or 4 neurologic toxicities, the most common of which were dysphasia (n=9) and confusion (n=8).
The researchers said all acute toxicities resolved completely, and none of the patients died as a result of toxicity.
One patient experienced vision loss 3 months after receiving CAR T-cell therapy. The researchers said they could not confirm the cause of the vision loss, but it is consistent with fludarabine toxicity.
One patient developed myelodysplastic syndrome, which was thought to be related to prior therapy.
The researchers noted that patients who experienced grade 3/4 neurologic toxicity had significantly higher levels of blood CAR+ cells than patients who had neurologic toxicities of a lower grade (P=0.003).
In addition, peak levels of serum IL-10 and IL-15 were higher in patients with grade 3/4 neurologic toxicities (P=0.006 and 0.014, respectively). 
When given after low-dose chemotherapy, an anti-CD19 chimeric antigen receptor (CAR) T-cell therapy can produce durable complete responses (CRs) in patients with relapsed/refractory non-Hodgkin lymphoma (NHL), according to research published in the Journal of Clinical Oncology.
In this phase 1 study, the overall response rate was 73%, and 50% of patients had an ongoing CR at last follow-up.
Fifty-five percent of patients experienced grade 3/4 neurologic toxicities, though these events eventually resolved.
This research was conducted under a cooperative research and development agreement between the National Cancer Institute and Kite Pharma, Inc.
Kite is developing the CAR T-cell therapy axicabtagene ciloleucel (formerly known as KTE-C19), and the therapy tested in this trial has the same CAR construct as axicabtagene ciloleucel.
Results from this study (NCT00924326) were previously published in the Journal of Clinical Oncology in 2014.
The current report included 22 patients with relapsed/refractory NHL. Seventeen patients had diffuse large B-cell lymphoma (DLBCL), 2 had primary mediastinal B-cell lymphoma (PMBCL), 2 had follicular lymphoma (FL), and 1 had mantle cell lymphoma (MCL).
Patients received a single dose of CAR T cells 2 days after a low-dose chemotherapy conditioning regimen consisting of cyclophosphamide and fludarabine.
Response
The overall response rate was 73% (16/22), with a CR rate of 55% (n=12) and a partial response (PR) rate of 18% (n=4).
Among patients with DLBCL, there were 9 CRs, 4 PRs, 1 patient with stable disease, and 3 patients with progressive disease.
Both FL patients achieved a CR, as did the patient with MCL. One patient with PMBCL had stable disease, and the other progressed.
Eleven of the 12 CRs are ongoing, with durations ranging from more than 7 months to more than 24 months. The median duration of CR is 12.5 months.
The researchers found that serum IL-15 levels and CAR T-cell expansion correlated with treatment response (CR or PR).
The median peak blood CAR+ cell level was 98/μL in patients who achieved a response and 15/μL in those who did not (P=0.027).
High serum IL-15 levels were significantly associated with high peak blood CAR+ cell levels (P=0.001) and response (P<0.001).
Toxicity
Fifty-five percent of patients had grade 3 or 4 neurologic toxicities, the most common of which were dysphasia (n=9) and confusion (n=8).
The researchers said all acute toxicities resolved completely, and none of the patients died as a result of toxicity.
One patient experienced vision loss 3 months after receiving CAR T-cell therapy. The researchers said they could not confirm the cause of the vision loss, but it is consistent with fludarabine toxicity.
One patient developed myelodysplastic syndrome, which was thought to be related to prior therapy.
The researchers noted that patients who experienced grade 3/4 neurologic toxicity had significantly higher levels of blood CAR+ cells than patients who had neurologic toxicities of a lower grade (P=0.003).
In addition, peak levels of serum IL-10 and IL-15 were higher in patients with grade 3/4 neurologic toxicities (P=0.006 and 0.014, respectively).
When given after low-dose chemotherapy, an anti-CD19 chimeric antigen receptor (CAR) T-cell therapy can produce durable complete responses (CRs) in patients with relapsed/refractory non-Hodgkin lymphoma (NHL), according to research published in the Journal of Clinical Oncology.
In this phase 1 study, the overall response rate was 73%, and 50% of patients had an ongoing CR at last follow-up.
Fifty-five percent of patients experienced grade 3/4 neurologic toxicities, though these events eventually resolved.
This research was conducted under a cooperative research and development agreement between the National Cancer Institute and Kite Pharma, Inc.
Kite is developing the CAR T-cell therapy axicabtagene ciloleucel (formerly known as KTE-C19), and the therapy tested in this trial has the same CAR construct as axicabtagene ciloleucel.
Results from this study (NCT00924326) were previously published in the Journal of Clinical Oncology in 2014.
The current report included 22 patients with relapsed/refractory NHL. Seventeen patients had diffuse large B-cell lymphoma (DLBCL), 2 had primary mediastinal B-cell lymphoma (PMBCL), 2 had follicular lymphoma (FL), and 1 had mantle cell lymphoma (MCL).
Patients received a single dose of CAR T cells 2 days after a low-dose chemotherapy conditioning regimen consisting of cyclophosphamide and fludarabine.
Response
The overall response rate was 73% (16/22), with a CR rate of 55% (n=12) and a partial response (PR) rate of 18% (n=4).
Among patients with DLBCL, there were 9 CRs, 4 PRs, 1 patient with stable disease, and 3 patients with progressive disease.
Both FL patients achieved a CR, as did the patient with MCL. One patient with PMBCL had stable disease, and the other progressed.
Eleven of the 12 CRs are ongoing, with durations ranging from more than 7 months to more than 24 months. The median duration of CR is 12.5 months.
The researchers found that serum IL-15 levels and CAR T-cell expansion correlated with treatment response (CR or PR).
The median peak blood CAR+ cell level was 98/μL in patients who achieved a response and 15/μL in those who did not (P=0.027).
High serum IL-15 levels were significantly associated with high peak blood CAR+ cell levels (P=0.001) and response (P<0.001).
Toxicity
Fifty-five percent of patients had grade 3 or 4 neurologic toxicities, the most common of which were dysphasia (n=9) and confusion (n=8).
The researchers said all acute toxicities resolved completely, and none of the patients died as a result of toxicity.
One patient experienced vision loss 3 months after receiving CAR T-cell therapy. The researchers said they could not confirm the cause of the vision loss, but it is consistent with fludarabine toxicity.
One patient developed myelodysplastic syndrome, which was thought to be related to prior therapy.
The researchers noted that patients who experienced grade 3/4 neurologic toxicity had significantly higher levels of blood CAR+ cells than patients who had neurologic toxicities of a lower grade (P=0.003).
In addition, peak levels of serum IL-10 and IL-15 were higher in patients with grade 3/4 neurologic toxicities (P=0.006 and 0.014, respectively).