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Photo courtesy of Penn Medicine
ORLANDO, FL—CTL019, a CD19 chimeric antigen receptor (CAR) T-cell therapy, can persist for 3 years or longer in children and young adults with relapsed/refractory acute lymphoblastic leukemia (ALL), according to the latest results of a pilot study.
This suggests CTL019 can offer long-term disease control without subsequent therapy, such as stem cell transplant, said study author Stephan Grupp, MD, PhD, of the University of Pennsylvania in Philadelphia.
Dr Grupp presented these results at the 2015 ASH Annual Meeting (abstract 681*).
Previously, Dr Grupp and his colleagues reported that CTL019 led to durable antitumor activity, including sustained complete responses (CRs) in adults and children with ALL (ASH 2012, NEJM 2013, ASH 2013, NEJM 2014, ASH 2014).
At this year’s ASH meeting, he reported on outcomes and longer follow-up of the first 59 patients with relapsed/refractory ALL treated in a pilot trial. The patients had a median age of 11 years.
The median follow-up was 12 months. Fifty-five patients (93%) achieved a CR at 1 month. Six patients went on to receive a transplant, and 1 patient went on to receive donor lymphocyte infusion.
The relapse-free survival was 76% at 6 months and 55% at 12 months. Overall survival was 79% at 12 months.
“There were no relapses past 1 year,” Dr Grupp said, noting that 18 patients beyond 1 year are in remission, and 13 patients have not received further therapy.
“We are able to get patients into remission,” he said, adding that response is similar at high and low disease burden.
“We see massive proliferation of CAR T cells. Prolonged CTL019 persistence is detected by flow cytometry. About 70% of patients maintain CAR T cells.”
Resistance was seen in 7% of patients due to failure of T cells to proliferate. One-third of recurrences occurred in those with CD19-positive relapse and two-thirds with CD19-negative relapse.
Dr Grupp noted that CTL019 has an impact on central nervous system (CNS) disease.
“We are able to control CNS disease,” he said. “We found no CNS relapses in patients who were treated, and 98% of them still have CTL019 in the cerebral spinal fluid.”
B-cell aplasia persists beyond 3.5 years in all responding patients. This is managed by immunoglobulin replacement.
“Patients in remission and with B-cell aplasia at 1 year are still alive at 2 to 3 years,” Dr Grupp said. “We do not know how long this will last and if B cells will recover.”
Severe cytokine release syndrome (CRS), observed in 88% of patients, is the principal toxicity. This is controlled with anti-IL6 therapy. Patients who are less likely to have CRS are those with a lower disease burden.
“IL-6 is a major player but does not predict CRS; it only correlates strongly with it,” Dr Grupp said.
Some toxicity is also associated with macrophage activation syndrome and neurotoxicity.
CTL019 was invented at The University of Pennsylvania but has been licensed to Novartis. Most of the researchers involved in this study reported research funding and/or consultancy payments from Novartis, and 1 researcher is employed by the company. 
*Data in the abstract differ from the presentation.
Photo courtesy of Penn Medicine
ORLANDO, FL—CTL019, a CD19 chimeric antigen receptor (CAR) T-cell therapy, can persist for 3 years or longer in children and young adults with relapsed/refractory acute lymphoblastic leukemia (ALL), according to the latest results of a pilot study.
This suggests CTL019 can offer long-term disease control without subsequent therapy, such as stem cell transplant, said study author Stephan Grupp, MD, PhD, of the University of Pennsylvania in Philadelphia.
Dr Grupp presented these results at the 2015 ASH Annual Meeting (abstract 681*).
Previously, Dr Grupp and his colleagues reported that CTL019 led to durable antitumor activity, including sustained complete responses (CRs) in adults and children with ALL (ASH 2012, NEJM 2013, ASH 2013, NEJM 2014, ASH 2014).
At this year’s ASH meeting, he reported on outcomes and longer follow-up of the first 59 patients with relapsed/refractory ALL treated in a pilot trial. The patients had a median age of 11 years.
The median follow-up was 12 months. Fifty-five patients (93%) achieved a CR at 1 month. Six patients went on to receive a transplant, and 1 patient went on to receive donor lymphocyte infusion.
The relapse-free survival was 76% at 6 months and 55% at 12 months. Overall survival was 79% at 12 months.
“There were no relapses past 1 year,” Dr Grupp said, noting that 18 patients beyond 1 year are in remission, and 13 patients have not received further therapy.
“We are able to get patients into remission,” he said, adding that response is similar at high and low disease burden.
“We see massive proliferation of CAR T cells. Prolonged CTL019 persistence is detected by flow cytometry. About 70% of patients maintain CAR T cells.”
Resistance was seen in 7% of patients due to failure of T cells to proliferate. One-third of recurrences occurred in those with CD19-positive relapse and two-thirds with CD19-negative relapse.
Dr Grupp noted that CTL019 has an impact on central nervous system (CNS) disease.
“We are able to control CNS disease,” he said. “We found no CNS relapses in patients who were treated, and 98% of them still have CTL019 in the cerebral spinal fluid.”
B-cell aplasia persists beyond 3.5 years in all responding patients. This is managed by immunoglobulin replacement.
“Patients in remission and with B-cell aplasia at 1 year are still alive at 2 to 3 years,” Dr Grupp said. “We do not know how long this will last and if B cells will recover.”
Severe cytokine release syndrome (CRS), observed in 88% of patients, is the principal toxicity. This is controlled with anti-IL6 therapy. Patients who are less likely to have CRS are those with a lower disease burden.
“IL-6 is a major player but does not predict CRS; it only correlates strongly with it,” Dr Grupp said.
Some toxicity is also associated with macrophage activation syndrome and neurotoxicity.
CTL019 was invented at The University of Pennsylvania but has been licensed to Novartis. Most of the researchers involved in this study reported research funding and/or consultancy payments from Novartis, and 1 researcher is employed by the company.
*Data in the abstract differ from the presentation.
Photo courtesy of Penn Medicine
ORLANDO, FL—CTL019, a CD19 chimeric antigen receptor (CAR) T-cell therapy, can persist for 3 years or longer in children and young adults with relapsed/refractory acute lymphoblastic leukemia (ALL), according to the latest results of a pilot study.
This suggests CTL019 can offer long-term disease control without subsequent therapy, such as stem cell transplant, said study author Stephan Grupp, MD, PhD, of the University of Pennsylvania in Philadelphia.
Dr Grupp presented these results at the 2015 ASH Annual Meeting (abstract 681*).
Previously, Dr Grupp and his colleagues reported that CTL019 led to durable antitumor activity, including sustained complete responses (CRs) in adults and children with ALL (ASH 2012, NEJM 2013, ASH 2013, NEJM 2014, ASH 2014).
At this year’s ASH meeting, he reported on outcomes and longer follow-up of the first 59 patients with relapsed/refractory ALL treated in a pilot trial. The patients had a median age of 11 years.
The median follow-up was 12 months. Fifty-five patients (93%) achieved a CR at 1 month. Six patients went on to receive a transplant, and 1 patient went on to receive donor lymphocyte infusion.
The relapse-free survival was 76% at 6 months and 55% at 12 months. Overall survival was 79% at 12 months.
“There were no relapses past 1 year,” Dr Grupp said, noting that 18 patients beyond 1 year are in remission, and 13 patients have not received further therapy.
“We are able to get patients into remission,” he said, adding that response is similar at high and low disease burden.
“We see massive proliferation of CAR T cells. Prolonged CTL019 persistence is detected by flow cytometry. About 70% of patients maintain CAR T cells.”
Resistance was seen in 7% of patients due to failure of T cells to proliferate. One-third of recurrences occurred in those with CD19-positive relapse and two-thirds with CD19-negative relapse.
Dr Grupp noted that CTL019 has an impact on central nervous system (CNS) disease.
“We are able to control CNS disease,” he said. “We found no CNS relapses in patients who were treated, and 98% of them still have CTL019 in the cerebral spinal fluid.”
B-cell aplasia persists beyond 3.5 years in all responding patients. This is managed by immunoglobulin replacement.
“Patients in remission and with B-cell aplasia at 1 year are still alive at 2 to 3 years,” Dr Grupp said. “We do not know how long this will last and if B cells will recover.”
Severe cytokine release syndrome (CRS), observed in 88% of patients, is the principal toxicity. This is controlled with anti-IL6 therapy. Patients who are less likely to have CRS are those with a lower disease burden.
“IL-6 is a major player but does not predict CRS; it only correlates strongly with it,” Dr Grupp said.
Some toxicity is also associated with macrophage activation syndrome and neurotoxicity.
CTL019 was invented at The University of Pennsylvania but has been licensed to Novartis. Most of the researchers involved in this study reported research funding and/or consultancy payments from Novartis, and 1 researcher is employed by the company.
*Data in the abstract differ from the presentation.