CAR T for B-ALL: Game Changer For Young Patients?

In just 4 years, there’s been a significant evolution in the profile of pediatric and young adult patients who’ve taken the chimeric antigen receptor (CAR) T-cell immunotherapy known as tisagenlecleucel (Kymriah) for relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL), a new industry-funded study finds.

It’s becoming more common for patients with less severe disease to undergo the treatment, often bypassing hematopoietic stem cell transplantation (HSCT), and survival is on the rise.

From 2018 to 2022, the percentage of patients in an international cohort who had disease burden of ≥50% fell from 18% to 4%, researchers reported at the annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago. Median relapse-free survival in patients who didn’t undergo post-infusion HSCT grew from 18 months in 2018 to 27 months in 2020. It was not estimable in 2021.

“This introduction of the therapy is changing the treatment landscape of how we look at refractory B-ALL, where the standard of care previously would be to proceed to transplant. This therapy is actually reducing the use of transplant, which has lots of morbidity and mortality associated with it,” Texas Children’s Cancer Center hematologist-oncologist Rayne H. Rouce, MD, who led the study, said in an interview.

Tisagenlecleucel received Food and Drug Administration approval in 2017, said Nirali N. Shah, MD, MHSc, head of the Pediatric Oncology Branch’s Hematologic Malignancies Section at the National Cancer Institute, in an interview. Dr. Shah is familiar with the study findings but didn’t take part in the research.

Remission rates have been around 60%-70%, Dr. Shah said, although that rate is “likely higher” now because of gains in experience and improvement in disease burden prior to therapy. 

The new findings fill a knowledge gap about real-world outcomes since a lot of the prior data was based on investigational CAR T-cell products, she said.

The noninterventional, prospective, longitudinal study, funded by tisagenlecleucel manufacturer Novartis, tracked 974 patients up to age 25 who received tisagenlecleucel in the United States, Canada, Korea, and Taiwan.

The study found that between 2018 and 2022:

• The percentage of patients who received treatment while in morphological complete remission grew from 34% to 51%.
• The percentages who were in third or greater relapse fell from 14% to 2%.
• The percentages undergoing ≥1 HSCT before tisagenlecleucel infusion fell from 37% to 15%.
• Overall, 34.5% of 911 patients received post-infusion HSCT.

In the big picture, the findings suggest that the therapy can be considered more than “a last resort for patients in a second or greater relapse or who are refractory,” Dr. Rouce said. By offering CAR T-cell therapy to earlier-stage patients, she said, “when they’re less sick, when they have less comorbidities, and when their organs are functioning better, we could potentially save them from having to go on to a transplant.”

Dr. Shah said the findings indicate that “a substantial number of patients are surviving. It’s remarkable actually. Prior to tisagenlecleucel, patients had dismal outcomes from standard chemotherapy.”

She added that the study suggests “providers are getting much more comfortable with getting their patients in the best shape prior to getting CAR T-cell therapy. Outcomes are improving as providers expand the use of CAR T-cell therapy to patients who are less heavily pretreated and have lower disease burden.”

Moving forward, “at some point there will likely be a plateau in terms of how good the outcomes can be.” And there will be discussion of the role of HSCT.

“We’ll figure out some of the nuances about which patients need transplants and which can avoid them. But curative potential is growing. With or without transplant, this is ultimately going to lead to a much higher fraction of patients being cured who previously would not have been cured,” she said. “That’s the bottom line.”

As for adverse effects, Dr. Shah said “disease burden has a pretty direct relationship with side effects and toxicities. If you have more disease, you have more severe side effects.”

Reducing disease burden will reduce side effects, she said. Also, “we’re getting a lot better at managing these toxicities. Eliminating some of the more toxic chemotherapy through earlier use of CAR T-cells in chemotherapy-refractory patients may well help reduce therapy burden and improve long-term survival outcomes, she added.

As for cost, drugs.com reports that the therapy runs to more than $612,000 per infusion. But Dr. Shah said insurers are covering the treatment. She added that there are efforts to expand the indication so CAR T-cell therapy can be used earlier in patients who are chemotherapy-refractory.

Novartis funded the study. Dr. Shah discloses ties with Lentigen, VOR, and CARGO, ImmunoACT, and Sobi. Dr. Rouce reports relationships with Pfizer and Novartis.

In just 4 years, there’s been a significant evolution in the profile of pediatric and young adult patients who’ve taken the chimeric antigen receptor (CAR) T-cell immunotherapy known as tisagenlecleucel (Kymriah) for relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL), a new industry-funded study finds.

It’s becoming more common for patients with less severe disease to undergo the treatment, often bypassing hematopoietic stem cell transplantation (HSCT), and survival is on the rise.

From 2018 to 2022, the percentage of patients in an international cohort who had disease burden of ≥50% fell from 18% to 4%, researchers reported at the annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago. Median relapse-free survival in patients who didn’t undergo post-infusion HSCT grew from 18 months in 2018 to 27 months in 2020. It was not estimable in 2021.

“This introduction of the therapy is changing the treatment landscape of how we look at refractory B-ALL, where the standard of care previously would be to proceed to transplant. This therapy is actually reducing the use of transplant, which has lots of morbidity and mortality associated with it,” Texas Children’s Cancer Center hematologist-oncologist Rayne H. Rouce, MD, who led the study, said in an interview.

Tisagenlecleucel received Food and Drug Administration approval in 2017, said Nirali N. Shah, MD, MHSc, head of the Pediatric Oncology Branch’s Hematologic Malignancies Section at the National Cancer Institute, in an interview. Dr. Shah is familiar with the study findings but didn’t take part in the research.

Remission rates have been around 60%-70%, Dr. Shah said, although that rate is “likely higher” now because of gains in experience and improvement in disease burden prior to therapy. 

The new findings fill a knowledge gap about real-world outcomes since a lot of the prior data was based on investigational CAR T-cell products, she said.

The noninterventional, prospective, longitudinal study, funded by tisagenlecleucel manufacturer Novartis, tracked 974 patients up to age 25 who received tisagenlecleucel in the United States, Canada, Korea, and Taiwan.

The study found that between 2018 and 2022:

• The percentage of patients who received treatment while in morphological complete remission grew from 34% to 51%.
• The percentages who were in third or greater relapse fell from 14% to 2%.
• The percentages undergoing ≥1 HSCT before tisagenlecleucel infusion fell from 37% to 15%.
• Overall, 34.5% of 911 patients received post-infusion HSCT.

In the big picture, the findings suggest that the therapy can be considered more than “a last resort for patients in a second or greater relapse or who are refractory,” Dr. Rouce said. By offering CAR T-cell therapy to earlier-stage patients, she said, “when they’re less sick, when they have less comorbidities, and when their organs are functioning better, we could potentially save them from having to go on to a transplant.”

Dr. Shah said the findings indicate that “a substantial number of patients are surviving. It’s remarkable actually. Prior to tisagenlecleucel, patients had dismal outcomes from standard chemotherapy.”

She added that the study suggests “providers are getting much more comfortable with getting their patients in the best shape prior to getting CAR T-cell therapy. Outcomes are improving as providers expand the use of CAR T-cell therapy to patients who are less heavily pretreated and have lower disease burden.”

Moving forward, “at some point there will likely be a plateau in terms of how good the outcomes can be.” And there will be discussion of the role of HSCT.

“We’ll figure out some of the nuances about which patients need transplants and which can avoid them. But curative potential is growing. With or without transplant, this is ultimately going to lead to a much higher fraction of patients being cured who previously would not have been cured,” she said. “That’s the bottom line.”

As for adverse effects, Dr. Shah said “disease burden has a pretty direct relationship with side effects and toxicities. If you have more disease, you have more severe side effects.”

Reducing disease burden will reduce side effects, she said. Also, “we’re getting a lot better at managing these toxicities. Eliminating some of the more toxic chemotherapy through earlier use of CAR T-cells in chemotherapy-refractory patients may well help reduce therapy burden and improve long-term survival outcomes, she added.

As for cost, drugs.com reports that the therapy runs to more than $612,000 per infusion. But Dr. Shah said insurers are covering the treatment. She added that there are efforts to expand the indication so CAR T-cell therapy can be used earlier in patients who are chemotherapy-refractory.

Novartis funded the study. Dr. Shah discloses ties with Lentigen, VOR, and CARGO, ImmunoACT, and Sobi. Dr. Rouce reports relationships with Pfizer and Novartis.

In just 4 years, there’s been a significant evolution in the profile of pediatric and young adult patients who’ve taken the chimeric antigen receptor (CAR) T-cell immunotherapy known as tisagenlecleucel (Kymriah) for relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL), a new industry-funded study finds.

It’s becoming more common for patients with less severe disease to undergo the treatment, often bypassing hematopoietic stem cell transplantation (HSCT), and survival is on the rise.

From 2018 to 2022, the percentage of patients in an international cohort who had disease burden of ≥50% fell from 18% to 4%, researchers reported at the annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago. Median relapse-free survival in patients who didn’t undergo post-infusion HSCT grew from 18 months in 2018 to 27 months in 2020. It was not estimable in 2021.

“This introduction of the therapy is changing the treatment landscape of how we look at refractory B-ALL, where the standard of care previously would be to proceed to transplant. This therapy is actually reducing the use of transplant, which has lots of morbidity and mortality associated with it,” Texas Children’s Cancer Center hematologist-oncologist Rayne H. Rouce, MD, who led the study, said in an interview.

Tisagenlecleucel received Food and Drug Administration approval in 2017, said Nirali N. Shah, MD, MHSc, head of the Pediatric Oncology Branch’s Hematologic Malignancies Section at the National Cancer Institute, in an interview. Dr. Shah is familiar with the study findings but didn’t take part in the research.

Remission rates have been around 60%-70%, Dr. Shah said, although that rate is “likely higher” now because of gains in experience and improvement in disease burden prior to therapy. 

The new findings fill a knowledge gap about real-world outcomes since a lot of the prior data was based on investigational CAR T-cell products, she said.

The noninterventional, prospective, longitudinal study, funded by tisagenlecleucel manufacturer Novartis, tracked 974 patients up to age 25 who received tisagenlecleucel in the United States, Canada, Korea, and Taiwan.

The study found that between 2018 and 2022:

• The percentage of patients who received treatment while in morphological complete remission grew from 34% to 51%.
• The percentages who were in third or greater relapse fell from 14% to 2%.
• The percentages undergoing ≥1 HSCT before tisagenlecleucel infusion fell from 37% to 15%.
• Overall, 34.5% of 911 patients received post-infusion HSCT.

In the big picture, the findings suggest that the therapy can be considered more than “a last resort for patients in a second or greater relapse or who are refractory,” Dr. Rouce said. By offering CAR T-cell therapy to earlier-stage patients, she said, “when they’re less sick, when they have less comorbidities, and when their organs are functioning better, we could potentially save them from having to go on to a transplant.”

Dr. Shah said the findings indicate that “a substantial number of patients are surviving. It’s remarkable actually. Prior to tisagenlecleucel, patients had dismal outcomes from standard chemotherapy.”

She added that the study suggests “providers are getting much more comfortable with getting their patients in the best shape prior to getting CAR T-cell therapy. Outcomes are improving as providers expand the use of CAR T-cell therapy to patients who are less heavily pretreated and have lower disease burden.”

Moving forward, “at some point there will likely be a plateau in terms of how good the outcomes can be.” And there will be discussion of the role of HSCT.

“We’ll figure out some of the nuances about which patients need transplants and which can avoid them. But curative potential is growing. With or without transplant, this is ultimately going to lead to a much higher fraction of patients being cured who previously would not have been cured,” she said. “That’s the bottom line.”

As for adverse effects, Dr. Shah said “disease burden has a pretty direct relationship with side effects and toxicities. If you have more disease, you have more severe side effects.”

Reducing disease burden will reduce side effects, she said. Also, “we’re getting a lot better at managing these toxicities. Eliminating some of the more toxic chemotherapy through earlier use of CAR T-cells in chemotherapy-refractory patients may well help reduce therapy burden and improve long-term survival outcomes, she added.

As for cost, drugs.com reports that the therapy runs to more than $612,000 per infusion. But Dr. Shah said insurers are covering the treatment. She added that there are efforts to expand the indication so CAR T-cell therapy can be used earlier in patients who are chemotherapy-refractory.

Novartis funded the study. Dr. Shah discloses ties with Lentigen, VOR, and CARGO, ImmunoACT, and Sobi. Dr. Rouce reports relationships with Pfizer and Novartis.