A prospective trial of risk-stratified treatment of relapsed anaplastic large cell lymphoma (ALCL) provides evidence for allogeneic hematopoietic stem cell transplantation (SCT) as standard consolidation therapy in pediatric patients with progression during frontline therapy or relapse of a CD3-positive ALCL. The study results also support vinblastine monotherapy for the treatment of late relapses.

The ALCL-Relapse trial (ClinicalTrials.gov identifier: NCT00317408), which was published in the Journal of Clinical Oncology, appears to be the first prospective trial on relapsed ALCL. The main objective was to assess the efficacy of risk-stratified reinduction and consolidation, by allogeneic or autologous SCT and vinblastine monotherapy, for children with refractory or relapsed ALCL.

Patients were stratified according to the time of relapse and CD3 expression. Those with progression during frontline therapy were considered “very high risk”, while those with a CD3-positive relapse were considered “high risk”, and both of these groups received allogeneic SCT after reinduction chemotherapy.

An initial group of patients with a CD3-negative relapse within 1 year of their initial diagnosis or prior exposure to vinblastine were considered “intermediate risk” and received autologous SCT after carmustine-etoposide-cytarabine-melphalan; however, after premature termination of this arm, subsequent patients in the intermediate-risk group and low-risk patients who had CD3-negative relapse 1 year or more after their initial diagnosis received vinblastine monotherapy.


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The analysis included 105 evaluable patients with CNS-negative disease (median age, 12.4 years; range, 0.8-21.3 years); the patient population was 71% male.  Among the risk groups, there were 17 very high-risk patients, 26 high-risk patients, 32 intermediate-risk patients, and 21 low-risk patients (4 did not have risk group information available). The median follow-up duration was 8.1 years (range, 2.2-14.6 years).

Overall, the 5-year event-free survival (EFS) and overall survival (OS) were 53% ± 5% and 78% ± 4%, respectively. Among subgroups, the EFS rate was 41% ± 12% in the very-high-risk group, 62% ± 10% in the high-risk group, 44% ± 9% in the intermediate-risk group, and 81% ± 9% in the low-risk group. The OS rate was 59% ± 12% in the very high-risk group, 73% ± 9% in the high-risk group, 78% ± 7% in the intermediate-risk group, and 90% ± 6% in the low-risk group.

Among patients in the intermediate-risk group who had received autologous SCT (23 patients), the EFS and OS rates were 30% ± 10% and 78% ± 9%, respectively. All 5 patients with intermediate risk who received vinblastine monotherapy experienced subsequent relapse.

The main limitation of this study was the trial’s implementation of treatment recommendations only in some countries, which caused a discrepancy between the treatment recommendations and the actual treatments that patients received. While 90% of patients in the very high-risk and high-risk groups received recommended treatments, only 70% of patients in the intermediate-risk group received the recommended autologous SCT. The authors corrected for these changes in their statistical analyses.

“Allogeneic SCT offers a chance for cure in patients with high-risk ALCL relapse,” wrote the authors. “For early relapsed ALCL autologous SCT was not effective. Vinblastine monotherapy achieved cure in patients with late relapse; however, it was not effective for early relapses,” they concluded.

Disclosures: Some authors have declared affiliations with or received funding from the pharmaceutical industry. Please refer to the original study for a full list of disclosures.

Reference

Knörr F, Brugières 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. Published online July 30, 2020. doi:10.1200/JCO.20.00157