Outcome of childhood ALK-positive anaplastic large cell lymphoma relapses: Real-life experience of the French Society of Pediatric Oncology (SFCE) cohort of 75 French children.

Objective: To describe treatments and outcomes of French children treated for relapsed/refractory anaplastic lymphoma kinase-positive anaplastic large cell lymphoma (ALK+ ALCL).

Methods: We conducted the analysis of a series of 75 French children treated for a first relapsed/refractory ALK+ ALCL between 1999 and 2017.

Results: The median time to first relapse was 8.1 months from initial diagnosis (2.9 after end of treatment), with 12 relapses during frontline treatment or within 1 month of the end of treatment. Treatment of the first relapse varied according to the period of time and risk factors: 48 received multiagent chemotherapy, including 21 and 19 consolidated with allogeneic stem cell transplantation (SCT) and autologous-SCT, respectively. Twenty-one patients received weekly vinblastine, and six received ALK inhibitors (ALKi). Overall, 64/75 patients reached a second complete remission (CR2). Eight out of 11 patients who did not reach CR2 died and the other three were rescued with ALKi, vinblastine, and nivolumab. With a median follow-up of 8.2 years, 60 patients are alive, 43 in CR2, 15 in CR3, two in CR4; and 15 patients died, six from toxicity and nine from disease progression. The 5-year event-free survival and overall survival after first relapse were 51.7% (95% confidence interval [CI]: 39.6%-62.6%) and 80.7% (95% CI: 69.6%-88.1%), respectively. Time to relapse greater than 12 months from initial diagnosis was proven to be a prognostic factor in relapsed/refractory ALK+ ALCL.

Conclusion: In relapsed ALK+ ALCL, high survival rate can be reached with various therapeutic strategies. The main challenge remains to prevent subsequent relapses, and to lower long-term morbidity.