Adolescents and young adults with aggressive mature B-cell non-Hodgkin lymphomas appear to have better outcomes when they’re treated under pediatric protocols rather than adult regimens, Canadian investigators say.
Results of a study of patients from the ages of 15 to 21 years with either diffuse large B-cell lymphoma (DLBCL) or Burkitt’s lymphoma treated at regional or community cancer centers in the province of Ontario indicated that adolescents and young adult (AYA) patients treated at adult centers had a more than fourfold risk for disease relapse or progression, compared with their counterparts who were treated at pediatric centers, reported Sumit Gupta, MD, PhD, from the Hospital for Sick Children in Toronto and colleagues.
“Our data suggest that pediatric approaches are associated with improved event-free survival and overall survival, primarily due to a decrease in the risk of relapse or progression, while still using lower cumulative doses of chemotherapy,” he said in an oral abstract presented at the American Society of Hematology annual meeting, held virtually.
The findings echo those seen in the treatment of patients with acute lymphoblastic leukemia (ALL). As previously reported, a study from Nordic and Baltic countries showed that young adults with ALL who were treated with a pediatric regimen had a 4-year event-free survival rate of 73%, compared with 42% for historical controls.
Similarly, a prospective U.S. study reported in 2014 showed that AYA with ALL treated with a pediatric regimen had better overall and event-free survival rates, compared with historical controls.
As with ALL, pediatric and adult regimens for treatment of patients with aggressive mature B-cell NHL differ substantially, with pediatric patients receiving more intensive short-term therapy with lower cumulative doses.
In addition, while pediatric regimens for DLBCL and Burkitt’s lymphoma are identical, adult regimens differ substantially between the two histologies, Dr. Gupta pointed out.
Adult regimens for DLBCL most often incorporate CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) or CHOP plus rituximab (R-CHOP), whereas Burkitt’s lymphoma in adults is generally treated with more aggressive multidrug regimens, in combination with rituximab.
Rituximab was incorporated into adults’ regimens far earlier than in pediatric regimens, with Food and Drug Administration approval of rituximab in frontline therapy of adults with DLBCL in 2006, “whereas the first pediatric large-scale randomized controlled trial of rituximab in pediatric mature B-cell lymphoma was only published earlier this year,” he noted.
Population-based study
To see how treatment patterns for AYA patients with aggressive mature B-cell non-Hodgkin lymphomas differ between pediatric and adult centers, Dr. Gupta and colleagues conducted a population-based study of all AYA in Ontario diagnosed with Burkitt’s or DLBCL from the ages of 15 to 21 years from 1992 through 2012.
AYA from the ages of 15 to 18 years who were treated at pediatric centers were identified through the Provincial Pediatric Oncology Registry, which includes data on demographics, disease treatment, and outcomes from each of Ontario’s five childhood cancer treatments centers.
Adolescents and young adults from 15 to 21 years who were treated at adult centers with adult regimens were identified through the Ontario Cancer Registry using chart abstraction by trained personnel at all treatment centers, with all data validated by clinician reviewers.
A total of 176 patients were identified, 129 with DLBCL and 47 with Burkitt’s lymphoma. In all, 62 of the 176 patients (35.2%) were treated in pediatric centers. Not surprisingly, multivariable analysis showed that AYA treated in adult centers were older, and more likely to have been treated earlier in the study period.
Comparing treatment patterns by locus of care, the investigators found that patients with DLBCL in pediatric centers received half of the cumulative anthracycline doses as those in adult centers (150 mg/m2 vs. 300 mg/m2; P < .001) and about 75% of cumulative alkylating agent doses (3,300 mg/m2 vs. 4,465 mg/m2; P = .009).
Patients with Burkitt’s lymphoma had identical exposures to anthracyclines in pediatric vs. adult centers (120 mg/m2), but those treated in pediatric centers had half the exposure to alkylators as those treated in adult centers (3,300 mg/m2 vs. 6,600 mg/m2; P = .03).
Among patients with DLBCL, none of those treated at pediatric centers received rituximab, compared with 32.3% of those treated at adult centers (P < .001), whereas only a handful of patients with Burkitt’s lymphoma received rituximab in both pediatric and adult centers (nonsignificant).
Among all patients. 5-year event-free survival was 82.3% for those treated in pediatric centers, compared with 66.7% for those treated in adult centers (P = .02). Respective 5-year overall survival rates were 85.5% and 71.1% (P = .03).
Looking at survival by histology, the investigators saw that 5-year event-free survival for patients with DLBCL was 83.3% when they were treated like children vs. 66.7% when they were treated like adults (P = .04). Respective 5-year overall survival rates were 88.9% and 72% (P = .04).
Both event-free survival (80.8% vs. 66.7%) and overall survival (80.8% vs. 66.7%) were numerically but not statistically higher among patients with Burkitt’s treated at pediatric vs. adult centers.
An analysis adjusting for disease histology, stage, and time period of diagnosis showed that treatment at an adult center was associated with higher risk for death, with a hazard ratio of 2.4 (P = .03).
Additionally, an analysis adjusted for age, disease stage, and histology showed that patients treated in adult centers had a significantly increased risk of relapse or progression, compared with a HR of 4.4 (95% confidence interval; P = .008).
There were no significant differences in the risk of treatment-related mortality between the center types, however.
“It is important to note, however, that pediatric approaches to mature B-cell NHL [non-Hodgkin lymphoma] are associated with increased inpatient needs as compared to adult approaches, and with greater supportive care requirements. Thus the safety of such approaches in adults centers need to be established,” Dr. Gupta said.