Predictive Study On The Efficacy Of Crizotinib In The Treatment Of ALK-positive Anaplastic Large Cell Lymphoma

Background and objective : Anaplastic large cell lymphoma(ALCL)is a rare subtype of peripheral T-cell lymphoma,accounting for 3% to 5% of non?Hodgkin’s lymphoma.With the development of targeted therapies in recent years,the therapeutic efficacy of anaplastic large cell lymphoma(ALCL)was improved,but still 30%～40% of patients face the risk of recurrence and refractory.Crizotinib was the first tyrosine kinase inhibitor to treat of anaplastic lymphoma kinase(ALK)positive ALCL.The effectiveness of crizotinib combined with chemotherapy in anaplastic lymphoma kinase(ALK)-positive ALCL was proved.However,some patients still have no efficacy in the combination therapy of crizotinib and chemotherapy.This study hopes to screen the potential population who would benefit from the targeted therapy of crizotinib by comparing the two most commonly used assays in the clinic,Fluorescence in situ hybridization(FISH)and immunohistochemistry(IHC),to achieve the precision targeted therapy for ALK-positive ALCL patients.Methods:This study retrospectively collected ALK-positive ALCL patients who treated with crizotinib combined with chemotherapy from Sichuan Cancer Hospital and Sun Yat sen University Cancer Center from June 2016 to October 2022.We detected the ALK gene translocation status of the ALK-positive ALCL patients by LIS ALK probes.We further divided the results of VENTANA ALK into IHC1+,IHC2+,and IHC3+ based on the degree and area of cell staining in pathological sections.Results:A total of 37 ALK-positive ALCL patients were included in this study,with a median follow-up time of 38 months(20-60 months).The objective response rate(ORR)of the entire group was 48.6%,and the 3-year progression free survival(PFS)and 3-year overall survival(OS)rates were 21.6% and 56.8%,respectively.In this study,the detection results of FISH of 24 patients were positive,of which 7 were IHC2+and 17 were IHC3+;the detection results of FISH of 14 patients were negative,of which 3 were IHC2+and 10 were IHC1+.The ORR,3-year PFS,and 3-year OS of the FISH+ group were significantly higher than those of the FISH-group(ORR: 62.5% vs 23.1%,P=0.038;3-year PFS: 25.0% vs 7.7%,P=0.0001;3-year OS: 75.0% vs 15.4%,P=0.0004).The 3-year PFS and 3-year OS of the FISH+IHC3+ group were higher than those of the FISH+IHC2+ group(3-year PFS: 35.3% vs 14.3%,P=0.133;3-year OS: 76.5% vs 57.1%,P=0.156).The 3-year PFS and 3-year OS of FISH+IHC2+ group were higher than those of FISH IHC1+/2+(3-year PFS: 14.3% vs 7.7%,P=0.029;3-year OS: 57.1% vs 15.4%,P=0.017).Conclusion : 1.The results of FISH can accurately predict the efficacy and prognosis of crizotinib in the treatment of ALK+ALCL patients.2.IHC3+ may be a potential indicator for predicting the efficacy and prognosis of crizotinib in treatment of ALK+ALCL patients.