Early PET response predicts the risk of relapse after 2L axi-cel in large B-cell lymphoma

Patients with large B-cell lymphoma who progress after second-line (2L) chimeric antigen receptor T cell (CAR T) therapy have an increasing number of post-CAR T treatment options available and should be considered for timely intervention if at high risk of CAR T failure. In this national cohort of 302 patients receiving 2L axicabtagene ciloleucel (axi-cel), we assessed the use of early fluorodeoxyglucose positron emission tomography (PET) response to guide post-CAR T management. A total of 245 patients with treatment response at 1 month were grouped according to depth of response by Deauville score (DS): complete metabolic response or focal residual activity in the bridging radiotherapy field (DS1-3/DS4RT), partial response (PR) DS4, and PR DS5. DS response categories were significantly associated with risk of progression, progression-free survival, and overall survival. Patients with DS4 and DS5 response had a 50% and 73% risk of progression by month 6, respectively, compared with 25% for DS1-3/DS4RT (DS4: hazard ratio [HR], 3.07 [95% CI: 1.85-5.07] and DS5: HR, 5.20 [95% CI: 2.95-9.16]; P< .0001), which was independently significant in multivariable analyses. In a risk model using DS categories and preinfusion lactate dehydrogenase levels ≥2 upper limit of normal, we identified a high-risk group with significant risk of early failure (HR, 5.21 [95% CI: 3.27-8.29]; P< .001). Our results demonstrate the prognostic value of early PET response in patients treated with 2L axi-cel, independent of preinfusion risk factors. Responding high-risk patients had ≥70% risk of progression by month 6 and should be strongly considered for early post-CAR T therapies.