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“This real-world study demonstrates that CD19 CAR-T cell therapy is feasible in a population of patients aged 75 years and older,” said senior author Pierre Bories, MD, PhD, of the Institute for Cancer Strasbourg-Europe, in Alsace, France. He presented the findings at the annual meeting of the European Hematology Association, held in Madrid, Spain.
Patients with R/R LBCL are often older, with many aged over 75, yet patients in those age groups are frequently underrepresented in clinical trials of CD19-directed CAR T-cell therapy, which has significantly improved outcomes for patients with R/R LBCL.
To further investigate differences in outcomes between older and younger patients with R/R LBCL treated with CAR-T cell therapy, Dr. Bories and colleagues conducted a retrospective analysis of 1,524 patients in the French DESCAR-T registry who were treated at treated at 31 centers in France and had at least two previous infusions of CAR-T cell therapy between April 2018 and September 2023.
Of the patients, 69.8% (n = 1065) were treated with axicabtagene ciloleucel (axi-cel), while 30.1% (n = 459) were treated with tisagenlecleucel (tisa-cel).
Among those patients, 125 were 75 years old or older, with a median age of 76, and the remaining 1399 were under the age of 75, with a median age of 62.
The two age groups had significant differences in terms of characteristics including gender, LBCL subset, number of prior lines of therapy, performance status, age-adjusted International Prognostic Index (IPI), rate of patients receiving a bridging therapy, response to the bridging therapy, and LDH at time of infusion.
Compared with patients aged 75 or younger, those who were 75 years or older had a higher hematopoietic cell transplantation–specific comorbidity index (HCT-CI) score, (31.2% high HCT-CI versus 16.8%, respectively; P < .001).
Patients over 75 also had fewer prior transplants than those under 75 (4.8% versus 21.8%, respectively; P < .001), and they more commonly received tisa-cel CAR-T cell therapy (43.2% versus 28.9%, respectively; P < .001).
Among 1457 patients with response data available, with a median follow-up of 12.7 months, there were no significant differences in terms of the best overall response rate (ORR) and complete response rates (CRR) between the two age groups, with rates of 74.8% for ORR and 62.6% for CRR among those 75 or older, compared with 78.0% and 60.8%, respectively, in the under 75 group (P = .425 and P = .699, respectively).
Likewise, the estimated median overall survival (OS) was 18.3 months in the 75 and older group and 24.0 months in the under 75 group (P = .12).
There were also no significant difference in terms of the estimated median progression-free survival, of 8.2 months in the 75 and older group versus 6.1 months in the under 75 group (P = .73).
In terms of safety, there were no significant differences in terms of grade 3 or higher cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) among patients 75 and older versus under 75, with 7.3% versus 7.4% developing CRS, respectively (P = .97), and 9.8% versus 12.4% developing ICANS (P = .39).
There were no significant differences between the age groups regarding ICU admissions, which occurred in about 24% of the cohorts, or the need for mechanical ventilation, which was necessary in about 3% of the entire cohort.
Of note, the overall rates of non-relapse mortality were more common in the 75 years and older group, among whom 19.5% of deaths were not related to lymphoma progression or relapse, compared with 8.1% in the under 75 group (P < .0001).
Early mortalities not related to relapse, defined as occurring before day 28 post-infusion, occurred among 3 patients aged 75 and older (2.4% of all patients 75 and older, representing 12.0% of all non-relapse mortality cases) compared with 16 patients under 75 (1.2% of those patients and 13.1% of all non-relapse mortality).
Infection was the main cause of non-relapse mortality in both groups, representing the cause in 57.7% of those under 75 and 54.2% of those aged 75 and older.
Patients 75 and older had a significantly higher risk of non-relapse mortality from infection (P = .0003), CRS (P = .022) or other causes, compared with those under 75 (P = .0004), but not from ICANS (P = .524).
“Our findings show a higher non-relapse mortality in this older population, which mainly relied on late infectious events, occurring after 28 days,” Dr. Bories said.
“There was also a higher rate of non-relapse mortality from infections, CRS or other causes in those 75 or older, but that did not translate to a lower overall survival in our patient sample,” he said.
Asked at the session about the implications of the higher infection risk in elderly patients, Dr. Bories said, “I think this deserves special attention and we have to be more careful with frail patients.
“This should obviously encourage the use of prophylaxis for a longer period of time.”
Dr. Bories noted that he and his team are currently conducting a more detailed propensity-matched comparison between axi-cel and tisa-cel in an older population.
The findings are consistent with those of other studies, among the latest including a 2024 real-world multicenter study of 172 diffuse LBCL (DLBCL) patients treated with CAR-T cell therapy (mostly axi-cel).
That study showed comparable median progression-free and OS rates between those over and under the age of 70, however, in contrast to the current study, that study showed no significant differences in non-relapse mortality.
The ORR in that study also did not differ between age groups, exceeding 75%.
Of note, in that study, tisa‐cel treatment was associated with an approximately 60% higher risk of relapse and/or death compared with axi‐cel treatment, which the authors report was driven primarily by less favorable survival outcomes among tisa‐cel patients younger than age 70 years.
“In this context, some reports showed that axi‐cel may offer enhanced effectiveness compared to tisa‐cel in patients aged 65 and older, despite higher rates of neurotoxicity,” they wrote.
Nevertheless, the study’s overall findings indicate that “CAR T-cell therapy should be not withheld for elderly patients with r/r DLBCL,” the authors concluded.
Low CAR T Utilization in Elderly Patients
Overall, utilization of CAR-T cell therapy among older patients reportedly remains low, as demonstrated in one recent real-world study on the issue, involving 551 older patients with DLBCL.
The study showed that 19% of patients aged 65-69 and 22% of those aged 70-74 years received CAR-T cell therapy, compared with only 13% of those aged 75 and older.
“While CAR T-cell therapy in older patients is associated with favorable event-free survival comparable to outcomes in younger patients, CAR T-cell usage is low in older patients with DLBCL, which suggests an unmet need for more accessible, effective, and tolerable therapy,” reported first author Dia Chihara, MD, PhD, of the Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, in Houston, Texas, and colleagues.
Noting that “the use of current CAR-T cell therapy products seemed to be limited to selected patients,” the authors added that “this may change in the future with next-generation CAR T-cell therapy products.”
Dr. Bories disclosed relationships with Kite Gilead, Novartis, BMD-Celgene, Abbvie, Servier, Janssen and the BMS foundation.
“This real-world study demonstrates that CD19 CAR-T cell therapy is feasible in a population of patients aged 75 years and older,” said senior author Pierre Bories, MD, PhD, of the Institute for Cancer Strasbourg-Europe, in Alsace, France. He presented the findings at the annual meeting of the European Hematology Association, held in Madrid, Spain.
Patients with R/R LBCL are often older, with many aged over 75, yet patients in those age groups are frequently underrepresented in clinical trials of CD19-directed CAR T-cell therapy, which has significantly improved outcomes for patients with R/R LBCL.
To further investigate differences in outcomes between older and younger patients with R/R LBCL treated with CAR-T cell therapy, Dr. Bories and colleagues conducted a retrospective analysis of 1,524 patients in the French DESCAR-T registry who were treated at treated at 31 centers in France and had at least two previous infusions of CAR-T cell therapy between April 2018 and September 2023.
Of the patients, 69.8% (n = 1065) were treated with axicabtagene ciloleucel (axi-cel), while 30.1% (n = 459) were treated with tisagenlecleucel (tisa-cel).
Among those patients, 125 were 75 years old or older, with a median age of 76, and the remaining 1399 were under the age of 75, with a median age of 62.
The two age groups had significant differences in terms of characteristics including gender, LBCL subset, number of prior lines of therapy, performance status, age-adjusted International Prognostic Index (IPI), rate of patients receiving a bridging therapy, response to the bridging therapy, and LDH at time of infusion.
Compared with patients aged 75 or younger, those who were 75 years or older had a higher hematopoietic cell transplantation–specific comorbidity index (HCT-CI) score, (31.2% high HCT-CI versus 16.8%, respectively; P < .001).
Patients over 75 also had fewer prior transplants than those under 75 (4.8% versus 21.8%, respectively; P < .001), and they more commonly received tisa-cel CAR-T cell therapy (43.2% versus 28.9%, respectively; P < .001).
Among 1457 patients with response data available, with a median follow-up of 12.7 months, there were no significant differences in terms of the best overall response rate (ORR) and complete response rates (CRR) between the two age groups, with rates of 74.8% for ORR and 62.6% for CRR among those 75 or older, compared with 78.0% and 60.8%, respectively, in the under 75 group (P = .425 and P = .699, respectively).
Likewise, the estimated median overall survival (OS) was 18.3 months in the 75 and older group and 24.0 months in the under 75 group (P = .12).
There were also no significant difference in terms of the estimated median progression-free survival, of 8.2 months in the 75 and older group versus 6.1 months in the under 75 group (P = .73).
In terms of safety, there were no significant differences in terms of grade 3 or higher cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) among patients 75 and older versus under 75, with 7.3% versus 7.4% developing CRS, respectively (P = .97), and 9.8% versus 12.4% developing ICANS (P = .39).
There were no significant differences between the age groups regarding ICU admissions, which occurred in about 24% of the cohorts, or the need for mechanical ventilation, which was necessary in about 3% of the entire cohort.
Of note, the overall rates of non-relapse mortality were more common in the 75 years and older group, among whom 19.5% of deaths were not related to lymphoma progression or relapse, compared with 8.1% in the under 75 group (P < .0001).
Early mortalities not related to relapse, defined as occurring before day 28 post-infusion, occurred among 3 patients aged 75 and older (2.4% of all patients 75 and older, representing 12.0% of all non-relapse mortality cases) compared with 16 patients under 75 (1.2% of those patients and 13.1% of all non-relapse mortality).
Infection was the main cause of non-relapse mortality in both groups, representing the cause in 57.7% of those under 75 and 54.2% of those aged 75 and older.
Patients 75 and older had a significantly higher risk of non-relapse mortality from infection (P = .0003), CRS (P = .022) or other causes, compared with those under 75 (P = .0004), but not from ICANS (P = .524).
“Our findings show a higher non-relapse mortality in this older population, which mainly relied on late infectious events, occurring after 28 days,” Dr. Bories said.
“There was also a higher rate of non-relapse mortality from infections, CRS or other causes in those 75 or older, but that did not translate to a lower overall survival in our patient sample,” he said.
Asked at the session about the implications of the higher infection risk in elderly patients, Dr. Bories said, “I think this deserves special attention and we have to be more careful with frail patients.
“This should obviously encourage the use of prophylaxis for a longer period of time.”
Dr. Bories noted that he and his team are currently conducting a more detailed propensity-matched comparison between axi-cel and tisa-cel in an older population.
The findings are consistent with those of other studies, among the latest including a 2024 real-world multicenter study of 172 diffuse LBCL (DLBCL) patients treated with CAR-T cell therapy (mostly axi-cel).
That study showed comparable median progression-free and OS rates between those over and under the age of 70, however, in contrast to the current study, that study showed no significant differences in non-relapse mortality.
The ORR in that study also did not differ between age groups, exceeding 75%.
Of note, in that study, tisa‐cel treatment was associated with an approximately 60% higher risk of relapse and/or death compared with axi‐cel treatment, which the authors report was driven primarily by less favorable survival outcomes among tisa‐cel patients younger than age 70 years.
“In this context, some reports showed that axi‐cel may offer enhanced effectiveness compared to tisa‐cel in patients aged 65 and older, despite higher rates of neurotoxicity,” they wrote.
Nevertheless, the study’s overall findings indicate that “CAR T-cell therapy should be not withheld for elderly patients with r/r DLBCL,” the authors concluded.
Low CAR T Utilization in Elderly Patients
Overall, utilization of CAR-T cell therapy among older patients reportedly remains low, as demonstrated in one recent real-world study on the issue, involving 551 older patients with DLBCL.
The study showed that 19% of patients aged 65-69 and 22% of those aged 70-74 years received CAR-T cell therapy, compared with only 13% of those aged 75 and older.
“While CAR T-cell therapy in older patients is associated with favorable event-free survival comparable to outcomes in younger patients, CAR T-cell usage is low in older patients with DLBCL, which suggests an unmet need for more accessible, effective, and tolerable therapy,” reported first author Dia Chihara, MD, PhD, of the Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, in Houston, Texas, and colleagues.
Noting that “the use of current CAR-T cell therapy products seemed to be limited to selected patients,” the authors added that “this may change in the future with next-generation CAR T-cell therapy products.”
Dr. Bories disclosed relationships with Kite Gilead, Novartis, BMD-Celgene, Abbvie, Servier, Janssen and the BMS foundation.
“This real-world study demonstrates that CD19 CAR-T cell therapy is feasible in a population of patients aged 75 years and older,” said senior author Pierre Bories, MD, PhD, of the Institute for Cancer Strasbourg-Europe, in Alsace, France. He presented the findings at the annual meeting of the European Hematology Association, held in Madrid, Spain.
Patients with R/R LBCL are often older, with many aged over 75, yet patients in those age groups are frequently underrepresented in clinical trials of CD19-directed CAR T-cell therapy, which has significantly improved outcomes for patients with R/R LBCL.
To further investigate differences in outcomes between older and younger patients with R/R LBCL treated with CAR-T cell therapy, Dr. Bories and colleagues conducted a retrospective analysis of 1,524 patients in the French DESCAR-T registry who were treated at treated at 31 centers in France and had at least two previous infusions of CAR-T cell therapy between April 2018 and September 2023.
Of the patients, 69.8% (n = 1065) were treated with axicabtagene ciloleucel (axi-cel), while 30.1% (n = 459) were treated with tisagenlecleucel (tisa-cel).
Among those patients, 125 were 75 years old or older, with a median age of 76, and the remaining 1399 were under the age of 75, with a median age of 62.
The two age groups had significant differences in terms of characteristics including gender, LBCL subset, number of prior lines of therapy, performance status, age-adjusted International Prognostic Index (IPI), rate of patients receiving a bridging therapy, response to the bridging therapy, and LDH at time of infusion.
Compared with patients aged 75 or younger, those who were 75 years or older had a higher hematopoietic cell transplantation–specific comorbidity index (HCT-CI) score, (31.2% high HCT-CI versus 16.8%, respectively; P < .001).
Patients over 75 also had fewer prior transplants than those under 75 (4.8% versus 21.8%, respectively; P < .001), and they more commonly received tisa-cel CAR-T cell therapy (43.2% versus 28.9%, respectively; P < .001).
Among 1457 patients with response data available, with a median follow-up of 12.7 months, there were no significant differences in terms of the best overall response rate (ORR) and complete response rates (CRR) between the two age groups, with rates of 74.8% for ORR and 62.6% for CRR among those 75 or older, compared with 78.0% and 60.8%, respectively, in the under 75 group (P = .425 and P = .699, respectively).
Likewise, the estimated median overall survival (OS) was 18.3 months in the 75 and older group and 24.0 months in the under 75 group (P = .12).
There were also no significant difference in terms of the estimated median progression-free survival, of 8.2 months in the 75 and older group versus 6.1 months in the under 75 group (P = .73).
In terms of safety, there were no significant differences in terms of grade 3 or higher cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) among patients 75 and older versus under 75, with 7.3% versus 7.4% developing CRS, respectively (P = .97), and 9.8% versus 12.4% developing ICANS (P = .39).
There were no significant differences between the age groups regarding ICU admissions, which occurred in about 24% of the cohorts, or the need for mechanical ventilation, which was necessary in about 3% of the entire cohort.
Of note, the overall rates of non-relapse mortality were more common in the 75 years and older group, among whom 19.5% of deaths were not related to lymphoma progression or relapse, compared with 8.1% in the under 75 group (P < .0001).
Early mortalities not related to relapse, defined as occurring before day 28 post-infusion, occurred among 3 patients aged 75 and older (2.4% of all patients 75 and older, representing 12.0% of all non-relapse mortality cases) compared with 16 patients under 75 (1.2% of those patients and 13.1% of all non-relapse mortality).
Infection was the main cause of non-relapse mortality in both groups, representing the cause in 57.7% of those under 75 and 54.2% of those aged 75 and older.
Patients 75 and older had a significantly higher risk of non-relapse mortality from infection (P = .0003), CRS (P = .022) or other causes, compared with those under 75 (P = .0004), but not from ICANS (P = .524).
“Our findings show a higher non-relapse mortality in this older population, which mainly relied on late infectious events, occurring after 28 days,” Dr. Bories said.
“There was also a higher rate of non-relapse mortality from infections, CRS or other causes in those 75 or older, but that did not translate to a lower overall survival in our patient sample,” he said.
Asked at the session about the implications of the higher infection risk in elderly patients, Dr. Bories said, “I think this deserves special attention and we have to be more careful with frail patients.
“This should obviously encourage the use of prophylaxis for a longer period of time.”
Dr. Bories noted that he and his team are currently conducting a more detailed propensity-matched comparison between axi-cel and tisa-cel in an older population.
The findings are consistent with those of other studies, among the latest including a 2024 real-world multicenter study of 172 diffuse LBCL (DLBCL) patients treated with CAR-T cell therapy (mostly axi-cel).
That study showed comparable median progression-free and OS rates between those over and under the age of 70, however, in contrast to the current study, that study showed no significant differences in non-relapse mortality.
The ORR in that study also did not differ between age groups, exceeding 75%.
Of note, in that study, tisa‐cel treatment was associated with an approximately 60% higher risk of relapse and/or death compared with axi‐cel treatment, which the authors report was driven primarily by less favorable survival outcomes among tisa‐cel patients younger than age 70 years.
“In this context, some reports showed that axi‐cel may offer enhanced effectiveness compared to tisa‐cel in patients aged 65 and older, despite higher rates of neurotoxicity,” they wrote.
Nevertheless, the study’s overall findings indicate that “CAR T-cell therapy should be not withheld for elderly patients with r/r DLBCL,” the authors concluded.
Low CAR T Utilization in Elderly Patients
Overall, utilization of CAR-T cell therapy among older patients reportedly remains low, as demonstrated in one recent real-world study on the issue, involving 551 older patients with DLBCL.
The study showed that 19% of patients aged 65-69 and 22% of those aged 70-74 years received CAR-T cell therapy, compared with only 13% of those aged 75 and older.
“While CAR T-cell therapy in older patients is associated with favorable event-free survival comparable to outcomes in younger patients, CAR T-cell usage is low in older patients with DLBCL, which suggests an unmet need for more accessible, effective, and tolerable therapy,” reported first author Dia Chihara, MD, PhD, of the Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, in Houston, Texas, and colleagues.
Noting that “the use of current CAR-T cell therapy products seemed to be limited to selected patients,” the authors added that “this may change in the future with next-generation CAR T-cell therapy products.”
Dr. Bories disclosed relationships with Kite Gilead, Novartis, BMD-Celgene, Abbvie, Servier, Janssen and the BMS foundation.
FROM EHA 2024