Allogeneic SCT Benefits Children and Adolescents With Relapsed Anaplastic Large Cell Lymphoma

Findings from the International, Prospective ALCL-Relapse trial [NCT00317408] showed that allogeneic SCT after reinduction chemotherapy can lead to survival improvements in children and adolescents with high-risk relapsed or refractory anaplastic large cell lymphoma (ALCL), provide more insight into how to treat this population.

For patients with early-relapsed ALCL, data showed that autologous SCT wasn’t effective. 

“Current standard chemotherapy reaches an event-free survival (EFS) of 70% at 5 years in children with ALCL,” the study authors wrote. “Retrospective data on the outcome of pediatric relapsed ALCL show a survival after relapse of more than 50%.” In addition, there is no consensus on the optimal treatment approach in relapse, they explained.

Designed by the European Inter-Group for Childhood Non-Hodgkin Lymphoma, the prospective, stratified, multinational clinical trial was opened for patients at sites in 5 countries—the United Kingdom, Germany, Austria, Switzerland, and the Czech Republic.

Patients were stratified according to the time of relapse, CD3 expression, and prior vinblastine therapy to 3 different consolidation approaches: allogeneic hematopoietic stem cell transplantation (SCT), autologous SCT, or vinblastine monotherapy.

Those whose disease progressed during frontline therapy (very high risk) or with a CD3-positive relapse (high risk) received allogeneic SCT after reinduction chemotherapy. Patients with a CD3-negative relapse within 1 year after initial diagnosis or prior exposure to vinblastine (intermediate risk) received autologous SCT after carmustine, etoposide, cytarabine, and melphalan (BEAM). However, this arm was terminated prematurely, and patients received vinblastine monotherapy instead. Patients with a CD3-negative relapse more than 1 year after initial diagnosis (low risk) received by weekly vinblastine monotherapy (6 mg/m²; maximum, 10 mg) for 24 months.

Investigators analyzed 105 patients; most were male and had ALK-positive tumors. The median age was 12.4 years and median time from initial diagnosis to relapsed/refractory disease was 8.5 months. Patients were recruited from April 2004 to February 2014 and the median follow-up time was 8.1 years.

At 5 years, overall survival (OS) in patients with central nervous system–negative disease was 78% ± 4% and EFS, the primary endpoint, was 53% ± 5%.

Before termination of autologous SCT, EFS rates of patients in the very-high- (n = 17), high- (n = 26), intermediate- (n = 32), and low- (n = 21) risk groups were 41% ± 12%, 62% ± 10%, 44% ± 9%, and 81% ± 9%. The respective OS rates were 59% ± 12%, 73% ± 9%, 78% ± 7%, and 90% ± 6%.

Analyzing only the patients in the intermediate-risk group consolidated per protocol by autologous SCT, EFS and OS of 23 patients were 30% ± 10% and 78% ± 9%, respectively. The 5 patients with intermediate risk receiving vinblastine monotherapy experienced relapse again.

“Compared with data from retrospective analyses, the survival of patients with refractory or relapsed ALCL reached 75% in our prospective trial, demonstrating that relapsed ALCL remains a curable disease,” the study authors wrote.

The main limitation to the study was the implementation of the trial as treatment recommendation only in some countries, noted the authors. While recommendations were followed in approximately 90% of patients in the very high risk and high-risk groups, only 70% of patients in the intermediate risk group received autologous SCT, they explained.

Overall, investigators determined that patients with high-risk relapsed disease can benefit from allogeneic SCT and offer a chance for cure. 

A long-term remission rate of 81% by outpatient vinblastine monotherapy, with low risk for late effects in patients with a late relapse was also observed by investigators. However, the monotherapy wasn’t effective for early relapses. 

“Patients with early relapsed ALCL don’t benefit from consolidation by autologous SCT or vinblastine monotherapy,” the authors wrote. “However, they may benefit from clinical trials testing a consolidation approach including new targeted therapies. Targeted agents should be tested as reinduction for all but late relapses. Given the efficacy of vinblastine in relapse, this shift-of-paradigm approach should be tested for low-risk patients front line.”

Reference

1. Knorr F, Brugieres L, Pillon M, et al. Stem cell transplantation and vinblastine monotherapy for relapsed pediatric anaplastic large cell lymphoma: results of the international, prospective ALCL-relapse trial. J Clin Oncol. 2020;38(34):3999-4009. doi.org/10.1200/JCO.20.00157