Abstract

The introduction of CD19-specific chimeric antigen receptor T-cell therapy (CAR-T) for treatment of relapsed/refractory diffuse large B cell lymphoma (R/R DLBCL) gives hope to patients with otherwise dismal prognosis. Therapy outcomes, however, depend upon selection of patients and accurate early identification of non-responders. Patients treated with CAR-T usually undergo [18F]FDG PET-CT at time of decision (TD), time of CAR-T transfusion (TT), 1month (M1), and 3months (M3) post-therapy. The purpose of the current study was to identify the specific parameters that should be addressed when reporting PET-CT studies in the clinical setting of CAR-T therapy. A total of 138 PET-CT scans (30 TD, 42 TT, 44 M1, 22 M3) of 48 patients treated with CAR-T were included. SUVmax, TMTV, and TLG were calculated in all scans. Response was assessed using the Deauville scale and ΔSUVmax method. Overall survival (OS) was the primary endpoint. Median follow-up was 12.8 (IQR 6.4-16.0) months from CAR-T infusion. In a univariate analysis, TD-SUVmax > 17.1 and TT-SUVmax > 12.1 were associated with shorter OS (Pv < 0.05). In a multivariate analysis, three factors were significantly associated with shorter OS: TD-SUVmax > 17.1 (HR 10.3; Pv < 0.01), LDH > 450 U/l (HR 7.7; Pv < 0.01), and ECOG score > 1 (HR 5.5; Pv = 0.04). Data from TD and TT PET-CT scans were not predictive of toxicity. On M1-PET-CT, patients with a Deauville score > 3 had significantly shorter OS (median 7.9months, versus not reached, Pv < 0.01). ΔSUVmax ≤ 66% on M1-PET-CT predicted shorter OS when M1-SUVmax was compared to TD-SUVmax (Pv = 0.02) but not to TT-SUVmax (Pv = 0.38). Pre-treatment SUVmax may guide patient selection for CAR-T therapy. On M1-PET-CT, Deauville score and ΔSUVmax from TD may identify early therapy failure. These parameters are easy to obtain and should be included in the PET-CT report.

Highlights

  • Overall survival (OS) of patients with relapsed/refractory diffuse large B cell lymphoma (R/R relapsed/refractory diffuse large B-cell lymphoma (DLBCL)) who failed at least two treatment regimens is short, between 4.4–6.3 months [1, 2]

  • Three factors were significantly associated with shorter OS: TDSUVmax > 17.1 (HR 10.3; Pv 450 U/l (HR 7.7; Pv 1 (HR 5.5; Pv=0.04)

  • ΔSUVmax ≤ 66% on M1-PET-CT predicted shorter OS when comparison of M1-SUVmax was made to TDSUVmax (Pv=0.02) and not to T transfusion (TT)-SUVmax (Pv=0.38)

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Summary

Introduction

Overall survival (OS) of patients with relapsed/refractory diffuse large B cell lymphoma (R/R DLBCL) who failed at least two treatment regimens is short, between 4.4–6.3 months [1, 2]. This group of patients had limited treatment options prior to the recent approval of two commercially available CD19-specific chimeric antigen receptor T-cell (CAR-T) therapy, Axicabtagene ciloleucel (axi-cel) and Tisagenlecleucel (tisa-cel) [3,4,5]. Data from pivotal trials suggest durable remission in 30–40% of patient with R/R DLBCL treated with CAR-T therapy [4,5] This therapy is associated with toxicity, including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), which can be lifethreatening [6,7,8]. Non-responders should be identified as early as possible after CAR-T infusion so alteration of treatment approach may be considered

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