ALL: Asparaginase Tx Boosts Survival in AYA Patients

In the treatment of acute lymphoblastic leukemia/lymphoma (ALL), benefits observed in children and adults with an intensive regimen utilizing asparaginase extend to the adolescent and young adult population in a real-world setting.

“These findings of a large cohort of adolescents and young adults treated at a variety of U.S. centers confirm the findings of the clinical trial and also provide confidence that patients remaining on this regimen have very excellent 3-year outcomes,” senior author Lori S. Muffly, MD, associate professor of medicine at Stanford University in the Division of Blood and Marrow Transplantation and Cellular Therapy, in Stanford, California, said in an interview.

The study was presented at the American Society of Hematology annual meeting. In the Cancer and Leukemia Group B 10403 trial, the intensive asparaginase pediatric regimen, used in the adult oncology treatment setting, showed benefits in the adolescent and young adult population, with a 3-year event-free survival (EFS) rate of 59% and an overall survival rate of 73%.

Based on the results, the regimen has gained widespread utilization in the United States. However, evidence of the therapy’s safety and efficacy in real-world practice, outside of the controlled clinical trial setting, has been lacking.

To investigate, first author Dr. Muffly, along with coauthor Brandon DaSilva, MD, and colleagues at Stanford University School of Medicine conducted a retrospective analysis of 101 adolescent and young adult patients aged 17 to 40 with newly diagnosed Philadelphia chromosome (Ph)-negative B-cell ALL (B-ALL) or T-cell ALL (T-ALL).

The patients had been treated with the C10403 regimen off-trial at five U.S. centers between October 2012 and July 2020.

The study excluded Ph-positive or Burkitt-type ALL patients, in addition to those who were previously treated, with the exception of treatment with hydroxyurea, steroids, one dose of single-agent therapy, or rituximab for CD20-positive B-ALL. Of the patients, about half, 54%, were between the ages of 20 and 29; 69% were male and 55% were White. Most patients (70%) had B-cell immunophenotype, and among them, 49% had CD20 expression.

Forty percent of patients had normal karyotype; 3% were hypodiploid, 7% were KMT2a-rearranged, and 30% of the 27 patients assessed had Ph-like ALL. CNS involvement was present at diagnosis among 20% (9% with CNS2, 11% with CNS3) and 14% of patients had a mediastinal mass.

Of 71 patients with B-ALL, 16 (23%) received at least one dose of rituximab.

Among the 101 patients who started induction with C10403, 72 (71%) completed induction and continued to consolidation; 51 (50%) continued beyond consolidation, while only 31 (31%) completed the entire C10403 regimen through the end of maintenance.

For the primary outcomes, overall, the rate of induction response, defined as achieving <5% blasts on bone marrow by the end of induction or extended induction, was 91% of whom 54% were measurable residual disease [MRD]-negative (threshold of at least 10^–4).

The co-primary endpoint of 3-year event-free survival was 65% and 3-year overall survival was 82.7%.

Two deaths occurred (2%) among patients who were in remission and still receiving treatment.

Overall, 44 patients (44%) were taken off C10403 while in complete remission, including 20 (20%) to receive an allogeneic hematopoietic cell transplant (HCT), 23 (23%) to receive non-HCT alternative treatments including Hyper-CVAD or blinatumomab, and 1 (1%) for patient preference.

Dr. Muffly noted that the 31% of treatment completion is about the same as that seen on the original C10403 trial.

“In clinical practice, there are a variety of reasons that these patients came off therapy — probably the most common reason is for MRD-directed therapy, such as with blinatumomab.”

“We are currently analyzing the results of the patients who came off therapy relative to those who stayed on therapy which will be interesting.”

The slightly higher real-world 3-year EFS and OS (65% and 82.7%, respectively) compared with the outcomes in the clinical trial (59% and 73%, respectively), were “very encouraging,” Dr. Muffly noted.

“A lot has changed and improved in B-ALL for adolescent/young adults since this trial closed to enrollment over 10 years ago,” she explained.

“We have better MRD methods, MRD-directed therapies, and a variety of targeted immunotherapies being used in a variety of ways,” Dr. Muffly said. “The overall outcomes for adolescent/young adult ALL patients are improving and we can see that in this data set.”

Commenting on the study, Catherine Bollard, MD, a pediatric oncologist at Children’s National Hospital in Washington, DC, noted that the study’s retrospective nature is “definitely a major caveat that needs to be considered when evaluating the impact of the data.”

Regarding the relatively low rate of regimen completion, Dr. Bollard said, “I do think the pros still outweigh the cons. But getting patients into a deep complete remission and then evaluating their outcomes after consolidation with HCT or alternative therapy is certainly an important consideration and needs to be studied further in a larger cohort.”

Overall, however, “this ‘real world’ experience validates the use of this regimen outside of the clinical trial setting,” she said.

Dr. Muffly and Dr. Bollard had no disclosures to report. Dr. Bollard is the editor-in-chief of ASH’s journal, Blood Advances.

In the treatment of acute lymphoblastic leukemia/lymphoma (ALL), benefits observed in children and adults with an intensive regimen utilizing asparaginase extend to the adolescent and young adult population in a real-world setting.

“These findings of a large cohort of adolescents and young adults treated at a variety of U.S. centers confirm the findings of the clinical trial and also provide confidence that patients remaining on this regimen have very excellent 3-year outcomes,” senior author Lori S. Muffly, MD, associate professor of medicine at Stanford University in the Division of Blood and Marrow Transplantation and Cellular Therapy, in Stanford, California, said in an interview.

The study was presented at the American Society of Hematology annual meeting. In the Cancer and Leukemia Group B 10403 trial, the intensive asparaginase pediatric regimen, used in the adult oncology treatment setting, showed benefits in the adolescent and young adult population, with a 3-year event-free survival (EFS) rate of 59% and an overall survival rate of 73%.

Based on the results, the regimen has gained widespread utilization in the United States. However, evidence of the therapy’s safety and efficacy in real-world practice, outside of the controlled clinical trial setting, has been lacking.

To investigate, first author Dr. Muffly, along with coauthor Brandon DaSilva, MD, and colleagues at Stanford University School of Medicine conducted a retrospective analysis of 101 adolescent and young adult patients aged 17 to 40 with newly diagnosed Philadelphia chromosome (Ph)-negative B-cell ALL (B-ALL) or T-cell ALL (T-ALL).

The patients had been treated with the C10403 regimen off-trial at five U.S. centers between October 2012 and July 2020.

The study excluded Ph-positive or Burkitt-type ALL patients, in addition to those who were previously treated, with the exception of treatment with hydroxyurea, steroids, one dose of single-agent therapy, or rituximab for CD20-positive B-ALL. Of the patients, about half, 54%, were between the ages of 20 and 29; 69% were male and 55% were White. Most patients (70%) had B-cell immunophenotype, and among them, 49% had CD20 expression.

Forty percent of patients had normal karyotype; 3% were hypodiploid, 7% were KMT2a-rearranged, and 30% of the 27 patients assessed had Ph-like ALL. CNS involvement was present at diagnosis among 20% (9% with CNS2, 11% with CNS3) and 14% of patients had a mediastinal mass.

Of 71 patients with B-ALL, 16 (23%) received at least one dose of rituximab.

Among the 101 patients who started induction with C10403, 72 (71%) completed induction and continued to consolidation; 51 (50%) continued beyond consolidation, while only 31 (31%) completed the entire C10403 regimen through the end of maintenance.

For the primary outcomes, overall, the rate of induction response, defined as achieving <5% blasts on bone marrow by the end of induction or extended induction, was 91% of whom 54% were measurable residual disease [MRD]-negative (threshold of at least 10^–4).

The co-primary endpoint of 3-year event-free survival was 65% and 3-year overall survival was 82.7%.

Two deaths occurred (2%) among patients who were in remission and still receiving treatment.

Overall, 44 patients (44%) were taken off C10403 while in complete remission, including 20 (20%) to receive an allogeneic hematopoietic cell transplant (HCT), 23 (23%) to receive non-HCT alternative treatments including Hyper-CVAD or blinatumomab, and 1 (1%) for patient preference.

Dr. Muffly noted that the 31% of treatment completion is about the same as that seen on the original C10403 trial.

“In clinical practice, there are a variety of reasons that these patients came off therapy — probably the most common reason is for MRD-directed therapy, such as with blinatumomab.”

“We are currently analyzing the results of the patients who came off therapy relative to those who stayed on therapy which will be interesting.”

The slightly higher real-world 3-year EFS and OS (65% and 82.7%, respectively) compared with the outcomes in the clinical trial (59% and 73%, respectively), were “very encouraging,” Dr. Muffly noted.

“A lot has changed and improved in B-ALL for adolescent/young adults since this trial closed to enrollment over 10 years ago,” she explained.

“We have better MRD methods, MRD-directed therapies, and a variety of targeted immunotherapies being used in a variety of ways,” Dr. Muffly said. “The overall outcomes for adolescent/young adult ALL patients are improving and we can see that in this data set.”

Commenting on the study, Catherine Bollard, MD, a pediatric oncologist at Children’s National Hospital in Washington, DC, noted that the study’s retrospective nature is “definitely a major caveat that needs to be considered when evaluating the impact of the data.”

Regarding the relatively low rate of regimen completion, Dr. Bollard said, “I do think the pros still outweigh the cons. But getting patients into a deep complete remission and then evaluating their outcomes after consolidation with HCT or alternative therapy is certainly an important consideration and needs to be studied further in a larger cohort.”

Overall, however, “this ‘real world’ experience validates the use of this regimen outside of the clinical trial setting,” she said.

Dr. Muffly and Dr. Bollard had no disclosures to report. Dr. Bollard is the editor-in-chief of ASH’s journal, Blood Advances.

In the treatment of acute lymphoblastic leukemia/lymphoma (ALL), benefits observed in children and adults with an intensive regimen utilizing asparaginase extend to the adolescent and young adult population in a real-world setting.

“These findings of a large cohort of adolescents and young adults treated at a variety of U.S. centers confirm the findings of the clinical trial and also provide confidence that patients remaining on this regimen have very excellent 3-year outcomes,” senior author Lori S. Muffly, MD, associate professor of medicine at Stanford University in the Division of Blood and Marrow Transplantation and Cellular Therapy, in Stanford, California, said in an interview.

The study was presented at the American Society of Hematology annual meeting. In the Cancer and Leukemia Group B 10403 trial, the intensive asparaginase pediatric regimen, used in the adult oncology treatment setting, showed benefits in the adolescent and young adult population, with a 3-year event-free survival (EFS) rate of 59% and an overall survival rate of 73%.

Based on the results, the regimen has gained widespread utilization in the United States. However, evidence of the therapy’s safety and efficacy in real-world practice, outside of the controlled clinical trial setting, has been lacking.

To investigate, first author Dr. Muffly, along with coauthor Brandon DaSilva, MD, and colleagues at Stanford University School of Medicine conducted a retrospective analysis of 101 adolescent and young adult patients aged 17 to 40 with newly diagnosed Philadelphia chromosome (Ph)-negative B-cell ALL (B-ALL) or T-cell ALL (T-ALL).

The patients had been treated with the C10403 regimen off-trial at five U.S. centers between October 2012 and July 2020.

The study excluded Ph-positive or Burkitt-type ALL patients, in addition to those who were previously treated, with the exception of treatment with hydroxyurea, steroids, one dose of single-agent therapy, or rituximab for CD20-positive B-ALL. Of the patients, about half, 54%, were between the ages of 20 and 29; 69% were male and 55% were White. Most patients (70%) had B-cell immunophenotype, and among them, 49% had CD20 expression.

Forty percent of patients had normal karyotype; 3% were hypodiploid, 7% were KMT2a-rearranged, and 30% of the 27 patients assessed had Ph-like ALL. CNS involvement was present at diagnosis among 20% (9% with CNS2, 11% with CNS3) and 14% of patients had a mediastinal mass.

Of 71 patients with B-ALL, 16 (23%) received at least one dose of rituximab.

Among the 101 patients who started induction with C10403, 72 (71%) completed induction and continued to consolidation; 51 (50%) continued beyond consolidation, while only 31 (31%) completed the entire C10403 regimen through the end of maintenance.

For the primary outcomes, overall, the rate of induction response, defined as achieving <5% blasts on bone marrow by the end of induction or extended induction, was 91% of whom 54% were measurable residual disease [MRD]-negative (threshold of at least 10^–4).

The co-primary endpoint of 3-year event-free survival was 65% and 3-year overall survival was 82.7%.

Two deaths occurred (2%) among patients who were in remission and still receiving treatment.

Overall, 44 patients (44%) were taken off C10403 while in complete remission, including 20 (20%) to receive an allogeneic hematopoietic cell transplant (HCT), 23 (23%) to receive non-HCT alternative treatments including Hyper-CVAD or blinatumomab, and 1 (1%) for patient preference.

Dr. Muffly noted that the 31% of treatment completion is about the same as that seen on the original C10403 trial.

“In clinical practice, there are a variety of reasons that these patients came off therapy — probably the most common reason is for MRD-directed therapy, such as with blinatumomab.”

“We are currently analyzing the results of the patients who came off therapy relative to those who stayed on therapy which will be interesting.”

The slightly higher real-world 3-year EFS and OS (65% and 82.7%, respectively) compared with the outcomes in the clinical trial (59% and 73%, respectively), were “very encouraging,” Dr. Muffly noted.

“A lot has changed and improved in B-ALL for adolescent/young adults since this trial closed to enrollment over 10 years ago,” she explained.

“We have better MRD methods, MRD-directed therapies, and a variety of targeted immunotherapies being used in a variety of ways,” Dr. Muffly said. “The overall outcomes for adolescent/young adult ALL patients are improving and we can see that in this data set.”

Commenting on the study, Catherine Bollard, MD, a pediatric oncologist at Children’s National Hospital in Washington, DC, noted that the study’s retrospective nature is “definitely a major caveat that needs to be considered when evaluating the impact of the data.”

Regarding the relatively low rate of regimen completion, Dr. Bollard said, “I do think the pros still outweigh the cons. But getting patients into a deep complete remission and then evaluating their outcomes after consolidation with HCT or alternative therapy is certainly an important consideration and needs to be studied further in a larger cohort.”

Overall, however, “this ‘real world’ experience validates the use of this regimen outside of the clinical trial setting,” she said.

Dr. Muffly and Dr. Bollard had no disclosures to report. Dr. Bollard is the editor-in-chief of ASH’s journal, Blood Advances.