Discussion
The major challenge in treating pediatric ALCL is its high rate of relapse. Event-free survival rates have barely changed since the NHL-BFM first tested its B-cell NHL protocol on ALCL patients in the 1980s. Vinblastine has unusual efficacy as a single agent in relapsed ALCL when given for prolonged durations [2,3,9]. The experience with single-agent vinblastine in relapse therapy suggested it could be a potential drug in frontline therapy for pediatric ALCL. However, vinblastine inaccessibility poses a particular problem in mainland China and in the treatment of conditions such as relapsed ALCL [10].
This is the first report of single-drug vinorelbine in pediatric relapsed ALCL. All 4 patients achieved a CR. These results are comparable to the data from previous single-drug vinblastine studies for relapsed ALCL. Vinorelbine belongs to the second-generation vinca alkaloid compounds, which are more potent and less neurotoxic than vinblastine and vincristine. In addition, the availability of an oral formulation may be of particular interest in the treatment of ALCL. Maintenance therapy was shown to be highly efficient in relapsed ALCL and may produce durable remission [4].
Of interest, all 4 included patients received very high doses of vincristine in their initial treatment, suggesting an absence of cross-resistance between vinorelbine and other vinca alkaloid compounds. Indeed, the antiproliferative cascade triggered by vinca alkaloids at the molecular level is still unclear. About 90% of pediatric ALCL patients are positive for ALK fusion proteins, most of them caused by the t (2;5)(p23;q35) translocation. These translocations induce constitutive phosphorylation of ALK that activates multiple pathways such JAK/ATAT3, AKT/P13K, and RAS/ERK, leading to growth factor-independent cell proliferation and inhibition of apoptosis. The ERK pathway was found to be relevant to clinical response in predicting the effectiveness of vinorelbine in patients with non-small cell lung cancers [11].
In our series, the toxicity of vinorelbine has no impact on treatment schedule. Our findings suggest that vinorelbine is a potential therapeutic option for pediatric patients with recurrent ALCL and that the feasibility of delivering this regimen is satisfactory. The efficacy and safety of this single-drug regimen deserve to be evaluated on a large scale. We are now designing a clinical trial based on single-drug vinorelbine as salvage treatment for recurrent ALCL, which should be of interest in regard to pediatric patients with recurrent ALCL in China.
Disclosures: The authors have no conflicts of interest or funding to disclose.