2789 - Crizotinib Induction Followed by CHOP-Based Chemotherapy and Consolidative ISRT in a "Sandwich" Strategy for Bulky ALK-Positive Anaplastic Large Cell Lymphoma
Presenter(s)
T. Liu1,2, F. Zhu1, X. Liu1, G. Wu1, and L. Zhang1; 1Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China, Wuhan, China, 2Hubei Key Laboratory of Precision Radiation Oncology,Wuhan 430022, China, Wuhan, China
Purpose/Objective(s): We hypothesized that crizotinib induction followed by CHOP-based chemotherapy with consolidative involved-site radiotherapy (ISRT) would improve bulky-site control and reduce relapse in bulky ALK-positive anaplastic large cell lymphoma (ALK+ ALCL).
Materials/Methods: We retrospectively reviewed consecutive patients with newly diagnosed bulky ALK+ ALCL treated at one institution (2016–2023). Bulky disease was defined as maximum tumor diameter >10 cm. Patients received oral crizotinib induction (4 weeks), then CHOP-based chemotherapy (predominantly ECHOP) for 4–6 cycles, with planned ISRT to bulky sites delivered in a sandwich pattern after systemic therapy. ISRT was 30 Gy/15 fractions (de-escalated practice) or 36 Gy/18–20 fractions (earlier practice). Endpoints included complete response (CR), progression-free survival (PFS), overall survival (OS), and toxicity.
Results:
Sixteen patients were included (median age 29.5 years; 56% male); 69% had stage III–IV disease and median IPI was 2. All received crizotinib and ISRT to bulky disease (30 Gy: n=6; 36 Gy: n=10). CR was 100% (16/16), median time to CR 4.3 months. At median follow-up 85.1 months from diagnosis, no relapses (including at irradiated bulky sites) and no deaths occurred. The 5-year PFS and OS were both 100%. In the 30 Gy cohort, all remain in continuous CR at median follow-up 48.9 months.Although all patients experienced Grade 3–4 myelosuppression during the induction/systemic phase (Grade 4 in 94%), this hematologic toxicity was not temporally associated with ISRT. Critically, no Grade =2 acute toxicities attributable to radiotherapy were observed. No treatment-related mortality was observed.Conclusion:
A crizotinib-primed chemo-radiotherapy sandwich approach with consolidative ISRT achieved durable remission in bulky ALK+ ALCL, supporting an important role for ISRT in securing bulky-site control after effective systemic therapy. Toxicity was driven primarily by systemic therapy, with no evident RT-attributable adverse effects, supporting feasibility of consolidative ISRT. Dose-de-escalated ISRT (30 Gy/15 fractions) appears sufficient in this setting and warrants prospective validation.