Post-hoc analysis of induction failure in pediatric LCH: the JLSG-02 and LCH-12 clinical trials.

Treatment options for refractory multisystem Langerhans cell histiocytosis (LCH) were not well established prior to the era of targeted therapy. We evaluated the efficacy and safety of cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP)-like salvage regimen (Induction B) in patients with induction failure in a post-hoc analysis of the JLSG-02 (N = 147) and JPLSG LCH-12 (N = 107) studies of pediatric LCH. Of 254 patients, 41 were refractory (no response or progressive disease) following initial Induction A therapy (prednisolone, vincristine, and cytarabine). Among them, 35 patients who received Induction B therapy were analyzed. The overall response rate to Induction B was 66% (23/35). Sixteen patients (46%) achieved no active disease after Induction B followed by maintenance therapy; among them, six patients with risk organ involvement (RO+) relapsed. The 5-year overall survival was 100% in the RO- group and 84.6% (95% CI, 64.0-93.9%) in the RO+ group. Grade 3/4 hematological toxicities were frequent; however, no fatal adverse events were observed. Induction B demonstrated efficacy and an acceptable safety profile in pediatric refractory multisystem LCH. This therapy could be a salvage treatment option for patients with refractory disease when targeted therapy is not available.