New regimens for youth with T-cell malignancies yield best outcomes yet

A set of novel chemotherapy regimens yield excellent outcomes—the best yet—among pediatric and young adult patients with T-cell malignancies, finds a phase 3 randomized controlled trial conducted by the Children’s Oncology Group (ALL0434).

“Despite very intense and complex chemotherapy, 20% of children and adolescents enrolled in Children’s Oncology Group T-cell leukemia trials between 2000 and 2005 did not survive. New drugs were needed to improve survival rates for T-cell malignancies,” lead study author Kimberly P. Dunsmore, MD, a professor at Virginia Tech, Roanoke, said in a press briefing leading up to the annual meeting of the American Society of Clinical Oncology.

The ALL0434 trial tested the addition of methotrexate (Trexall) and/or nelarabine (Arranon), a T cell–specific drug known to be efficacious in relapsed disease, to standard chemotherapy, with tailoring of the regimen to recurrence risk. Analyses were based on 1,545 patients with T-cell acute lymphoblastic leukemia (T-ALL) or T-cell lymphoblastic lymphoma (T-LL).

Results for all patients with T-ALL showed that, with addition of either or both drugs, more than 90% were alive at 4 years and more than 80% were leukemia free. Adding nelarabine to standard chemotherapy improved disease-free survival among the subset having intermediate- or high-risk disease, and the best outcomes were seen with addition of both nelarabine and an escalating dose of methotrexate.

Although patients with T-LL did not see benefit from addition of nelarabine, they still had an 85% rate of overall survival at 4 years.

“ALL0434 is the largest trial for children and young adults with T-cell malignancy ever conducted. It has the best-ever survival data,” Dr. Dunsmore commented.

“Our next steps will be to examine what implications and benefits may accrue when using nelarabine in protocols without cranial irradiation. This is to decrease long-term neurologic side effects, and we think it may be possible since nelarabine also reduces CNS relapses,” she said.

 

“This trial highlights how effective our pediatric and young adult oncologists are at accruing: This is a rare disease, and they were able to put more than 1,500 patients on trial with this rare disease over the course of time,” commented ASCO President Bruce E. Johnson, MD, FASCO.

The new combination regimens are noteworthy in that they improved survival by an absolute 10% without minimal increase in toxicity, he maintained.

“This is part of the paradigm where nelarabine had been approved [by the FDA] for relapsed or recurrent disease, and in this particular setting, it has been moved upfront, closer to the initial treatment, improving the outcomes for those patients,” elaborated Dr. Johnson, who is also a professor of medicine at the Dana-Farber Cancer Institute and a leader of the Dana-Farber/Harvard Cancer Center Lung Cancer Program, both in Boston.

 

Study details

The ALL0434 trial enrolled patients aged 1-30 years with newly diagnosed T-ALL or T-LL. After induction chemotherapy, all patients received standard chemotherapy, the Children’s Oncology Group augmented Berlin-Frankfurt-Munster regimen (N Engl J Med. 1998;338:1663-71), and depending on recurrence risk, cranial irradiation.

In addition to that regimen, they were randomly assigned to four arms, according to methotrexate dosing (high dose with leucovorin rescue in the inpatient setting vs. escalating dose in the outpatient setting) and nelarabine therapy (receipt vs. nonreceipt).

Among patients with T-ALL, those with low-risk disease were ineligible for nelarabine and did not receive cranial irradiation, whereas those with intermediate- and high-risk disease were randomized to all four arms, Dr. Dunsmore explained. In addition, those who did not achieve remission on induction chemotherapy were nonrandomly assigned to the high-dose methotrexate plus nelarabine arm.

 

Patients with T-LL were ineligible for high-dose methotrexate and were randomized to escalating-dose methotrexate with or without nelarabine.

Among all patients with T-ALL, the 4-year rate of overall survival was 90.2%, and the 4-year rate of disease-free survival was 84.1%, Dr. Dunsmore reported.

Disease-free survival was better with escalating-dose methotrexate than with high-dose methotrexate (89.8% vs. 78%).

Addition of nelarabine for patients with T-ALL having intermediate- or high-risk disease improved disease-free survival, from 83% without the drug to 88% with the drug (P = .0450), and reduced the rate of CNS relapse. Disease-free survival was highest, at 91%, among those who received both escalating-dose methotrexate and nelarabine.

 

Among the patients who did not achieve remission from induction chemotherapy, the 4-year rate of overall survival was 54%. “This is important because it’s more than double the past survival rates,” Dr. Dunsmore noted.

Patients with T-LL fared similarly well whether they received nelarabine or not; fully 85% overall were still alive at 4 years.

In terms of adverse effects of nelarabine therapy, the rate of peripheral neuropathy (motor or sensory), one of the more problematic adverse effects of the drug, was 8% in the trial population overall and did not exceed 9% in any treatment arm, she reported.

Dr. Dunsmore disclosed that an immediate family member is an employee of and has a leadership role with TypeZero Technologies; that she receives travel, accommodations, and/or expenses from Novo Nordisk; and that an immediate family member receives travel, accommodations, and/or expenses from Tandem Diabetes Care. The study received funding from the Cancer Therapy Evaluation Program within the National Cancer Institute/National Institutes of Health and received support from the St. Baldrick’s Foundation.

SOURCE: Dunsmore KP et al. ASCO 2018, Abstract 10500.




 

A set of novel chemotherapy regimens yield excellent outcomes—the best yet—among pediatric and young adult patients with T-cell malignancies, finds a phase 3 randomized controlled trial conducted by the Children’s Oncology Group (ALL0434).

“Despite very intense and complex chemotherapy, 20% of children and adolescents enrolled in Children’s Oncology Group T-cell leukemia trials between 2000 and 2005 did not survive. New drugs were needed to improve survival rates for T-cell malignancies,” lead study author Kimberly P. Dunsmore, MD, a professor at Virginia Tech, Roanoke, said in a press briefing leading up to the annual meeting of the American Society of Clinical Oncology.

The ALL0434 trial tested the addition of methotrexate (Trexall) and/or nelarabine (Arranon), a T cell–specific drug known to be efficacious in relapsed disease, to standard chemotherapy, with tailoring of the regimen to recurrence risk. Analyses were based on 1,545 patients with T-cell acute lymphoblastic leukemia (T-ALL) or T-cell lymphoblastic lymphoma (T-LL).

Results for all patients with T-ALL showed that, with addition of either or both drugs, more than 90% were alive at 4 years and more than 80% were leukemia free. Adding nelarabine to standard chemotherapy improved disease-free survival among the subset having intermediate- or high-risk disease, and the best outcomes were seen with addition of both nelarabine and an escalating dose of methotrexate.

Although patients with T-LL did not see benefit from addition of nelarabine, they still had an 85% rate of overall survival at 4 years.

“ALL0434 is the largest trial for children and young adults with T-cell malignancy ever conducted. It has the best-ever survival data,” Dr. Dunsmore commented.

“Our next steps will be to examine what implications and benefits may accrue when using nelarabine in protocols without cranial irradiation. This is to decrease long-term neurologic side effects, and we think it may be possible since nelarabine also reduces CNS relapses,” she said.

 

“This trial highlights how effective our pediatric and young adult oncologists are at accruing: This is a rare disease, and they were able to put more than 1,500 patients on trial with this rare disease over the course of time,” commented ASCO President Bruce E. Johnson, MD, FASCO.

The new combination regimens are noteworthy in that they improved survival by an absolute 10% without minimal increase in toxicity, he maintained.

“This is part of the paradigm where nelarabine had been approved [by the FDA] for relapsed or recurrent disease, and in this particular setting, it has been moved upfront, closer to the initial treatment, improving the outcomes for those patients,” elaborated Dr. Johnson, who is also a professor of medicine at the Dana-Farber Cancer Institute and a leader of the Dana-Farber/Harvard Cancer Center Lung Cancer Program, both in Boston.

 

Study details

The ALL0434 trial enrolled patients aged 1-30 years with newly diagnosed T-ALL or T-LL. After induction chemotherapy, all patients received standard chemotherapy, the Children’s Oncology Group augmented Berlin-Frankfurt-Munster regimen (N Engl J Med. 1998;338:1663-71), and depending on recurrence risk, cranial irradiation.

In addition to that regimen, they were randomly assigned to four arms, according to methotrexate dosing (high dose with leucovorin rescue in the inpatient setting vs. escalating dose in the outpatient setting) and nelarabine therapy (receipt vs. nonreceipt).

Among patients with T-ALL, those with low-risk disease were ineligible for nelarabine and did not receive cranial irradiation, whereas those with intermediate- and high-risk disease were randomized to all four arms, Dr. Dunsmore explained. In addition, those who did not achieve remission on induction chemotherapy were nonrandomly assigned to the high-dose methotrexate plus nelarabine arm.

 

Patients with T-LL were ineligible for high-dose methotrexate and were randomized to escalating-dose methotrexate with or without nelarabine.

Among all patients with T-ALL, the 4-year rate of overall survival was 90.2%, and the 4-year rate of disease-free survival was 84.1%, Dr. Dunsmore reported.

Disease-free survival was better with escalating-dose methotrexate than with high-dose methotrexate (89.8% vs. 78%).

Addition of nelarabine for patients with T-ALL having intermediate- or high-risk disease improved disease-free survival, from 83% without the drug to 88% with the drug (P = .0450), and reduced the rate of CNS relapse. Disease-free survival was highest, at 91%, among those who received both escalating-dose methotrexate and nelarabine.

 

Among the patients who did not achieve remission from induction chemotherapy, the 4-year rate of overall survival was 54%. “This is important because it’s more than double the past survival rates,” Dr. Dunsmore noted.

Patients with T-LL fared similarly well whether they received nelarabine or not; fully 85% overall were still alive at 4 years.

In terms of adverse effects of nelarabine therapy, the rate of peripheral neuropathy (motor or sensory), one of the more problematic adverse effects of the drug, was 8% in the trial population overall and did not exceed 9% in any treatment arm, she reported.

Dr. Dunsmore disclosed that an immediate family member is an employee of and has a leadership role with TypeZero Technologies; that she receives travel, accommodations, and/or expenses from Novo Nordisk; and that an immediate family member receives travel, accommodations, and/or expenses from Tandem Diabetes Care. The study received funding from the Cancer Therapy Evaluation Program within the National Cancer Institute/National Institutes of Health and received support from the St. Baldrick’s Foundation.

SOURCE: Dunsmore KP et al. ASCO 2018, Abstract 10500.




 

A set of novel chemotherapy regimens yield excellent outcomes—the best yet—among pediatric and young adult patients with T-cell malignancies, finds a phase 3 randomized controlled trial conducted by the Children’s Oncology Group (ALL0434).

“Despite very intense and complex chemotherapy, 20% of children and adolescents enrolled in Children’s Oncology Group T-cell leukemia trials between 2000 and 2005 did not survive. New drugs were needed to improve survival rates for T-cell malignancies,” lead study author Kimberly P. Dunsmore, MD, a professor at Virginia Tech, Roanoke, said in a press briefing leading up to the annual meeting of the American Society of Clinical Oncology.

The ALL0434 trial tested the addition of methotrexate (Trexall) and/or nelarabine (Arranon), a T cell–specific drug known to be efficacious in relapsed disease, to standard chemotherapy, with tailoring of the regimen to recurrence risk. Analyses were based on 1,545 patients with T-cell acute lymphoblastic leukemia (T-ALL) or T-cell lymphoblastic lymphoma (T-LL).

Results for all patients with T-ALL showed that, with addition of either or both drugs, more than 90% were alive at 4 years and more than 80% were leukemia free. Adding nelarabine to standard chemotherapy improved disease-free survival among the subset having intermediate- or high-risk disease, and the best outcomes were seen with addition of both nelarabine and an escalating dose of methotrexate.

Although patients with T-LL did not see benefit from addition of nelarabine, they still had an 85% rate of overall survival at 4 years.

“ALL0434 is the largest trial for children and young adults with T-cell malignancy ever conducted. It has the best-ever survival data,” Dr. Dunsmore commented.

“Our next steps will be to examine what implications and benefits may accrue when using nelarabine in protocols without cranial irradiation. This is to decrease long-term neurologic side effects, and we think it may be possible since nelarabine also reduces CNS relapses,” she said.

 

“This trial highlights how effective our pediatric and young adult oncologists are at accruing: This is a rare disease, and they were able to put more than 1,500 patients on trial with this rare disease over the course of time,” commented ASCO President Bruce E. Johnson, MD, FASCO.

The new combination regimens are noteworthy in that they improved survival by an absolute 10% without minimal increase in toxicity, he maintained.

“This is part of the paradigm where nelarabine had been approved [by the FDA] for relapsed or recurrent disease, and in this particular setting, it has been moved upfront, closer to the initial treatment, improving the outcomes for those patients,” elaborated Dr. Johnson, who is also a professor of medicine at the Dana-Farber Cancer Institute and a leader of the Dana-Farber/Harvard Cancer Center Lung Cancer Program, both in Boston.

 

Study details

The ALL0434 trial enrolled patients aged 1-30 years with newly diagnosed T-ALL or T-LL. After induction chemotherapy, all patients received standard chemotherapy, the Children’s Oncology Group augmented Berlin-Frankfurt-Munster regimen (N Engl J Med. 1998;338:1663-71), and depending on recurrence risk, cranial irradiation.

In addition to that regimen, they were randomly assigned to four arms, according to methotrexate dosing (high dose with leucovorin rescue in the inpatient setting vs. escalating dose in the outpatient setting) and nelarabine therapy (receipt vs. nonreceipt).

Among patients with T-ALL, those with low-risk disease were ineligible for nelarabine and did not receive cranial irradiation, whereas those with intermediate- and high-risk disease were randomized to all four arms, Dr. Dunsmore explained. In addition, those who did not achieve remission on induction chemotherapy were nonrandomly assigned to the high-dose methotrexate plus nelarabine arm.

 

Patients with T-LL were ineligible for high-dose methotrexate and were randomized to escalating-dose methotrexate with or without nelarabine.

Among all patients with T-ALL, the 4-year rate of overall survival was 90.2%, and the 4-year rate of disease-free survival was 84.1%, Dr. Dunsmore reported.

Disease-free survival was better with escalating-dose methotrexate than with high-dose methotrexate (89.8% vs. 78%).

Addition of nelarabine for patients with T-ALL having intermediate- or high-risk disease improved disease-free survival, from 83% without the drug to 88% with the drug (P = .0450), and reduced the rate of CNS relapse. Disease-free survival was highest, at 91%, among those who received both escalating-dose methotrexate and nelarabine.

 

Among the patients who did not achieve remission from induction chemotherapy, the 4-year rate of overall survival was 54%. “This is important because it’s more than double the past survival rates,” Dr. Dunsmore noted.

Patients with T-LL fared similarly well whether they received nelarabine or not; fully 85% overall were still alive at 4 years.

In terms of adverse effects of nelarabine therapy, the rate of peripheral neuropathy (motor or sensory), one of the more problematic adverse effects of the drug, was 8% in the trial population overall and did not exceed 9% in any treatment arm, she reported.

Dr. Dunsmore disclosed that an immediate family member is an employee of and has a leadership role with TypeZero Technologies; that she receives travel, accommodations, and/or expenses from Novo Nordisk; and that an immediate family member receives travel, accommodations, and/or expenses from Tandem Diabetes Care. The study received funding from the Cancer Therapy Evaluation Program within the National Cancer Institute/National Institutes of Health and received support from the St. Baldrick’s Foundation.

SOURCE: Dunsmore KP et al. ASCO 2018, Abstract 10500.