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

Large B-cell lymphoma patients who progress after second-line (2L) CAR T 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 axi-cel, we assessed the use of early FDG PET response to guide post-CAR T management. 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 and overall survival. Patients with DS4 and DS5 response had a 50% and 73% risk of progression by month 6, respectively, compared to 25% for DS1-3/DS4RT (DS4: HR: 3.07 (1.85 - 5.07) and DS5: HR: 5.20 (2.95 - 9.16); p<0.0001), which was independently significant in multivariable analyses. In a risk model using DS categories and pre-infusion LDH levels ≥2ULN, we identified a high-risk group with significant risk of early failure (HR 5.21 (3.27 - 8.29) p<0.001). Our results demonstrate the prognostic value of early PET response in patients treated with 2L axi-cel, independent of pre-infusion 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.