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[18F]FDG PET-CT in patients with DLBCL treated with CAR-T cell therapy: a practical approach of reporting pre- and post-treatment studies

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Abstract

Purpose

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), 1 month (M1), and 3 months (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.

Methods

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.

Results

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 7.9 months, 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).

Conclusion

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.

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Data availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Abbreviations

R/R DLBCL:

Relapsed/refractory diffuse large B-cell lymphoma

CD19:

Cluster of differentiation 19

CAR-T:

Chimeric antigen receptor T-cell

CRS:

Cytokine release syndrome

ICANS:

Immune effector cell‐associated neurotoxicity syndrome

ECOG:

Eastern Cooperative Oncology Group

GCB:

Germinal center B-cell like

COO:

Cell of origin

[18F]FDG:

18F-fluorodeoxyglucose

PET-CT:

Positron emission tomography-computed tomography

TD:

Time of decision

TT:

Time of transfusion

M1:

1 Month

M3:

3 Months

SUVmax:

Maximum standardized uptake value

SUVmean:

Mean standardized uptake value

TMTV:

Total metabolic tumor volume

TLG:

Total lesion glycolysis

OS:

Overall survival

PFS:

Progression-free survival

IQR:

Interquartile range

Pv :

P-Value

CI:

Confidence interval

HR:

Hazard ratio

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Authors and Affiliations

  1. Department of Nuclear Medicine, Tel-Aviv Sourasky Medical Center, 6 Weizmann St, 6423906, Tel Aviv, Israel

    Dan Cohen, Shir Hazut Krauthammer & Einat Even-Sapir

  2. Institute of Hematology, Tel-Aviv Sourasky Medical Center, 6 Weizmann St, 6423906, Tel Aviv, Israel

    Efrat Luttwak, Ofrat Beyar-Katz, Yael Bar-On, Odelia Amit, Ronit Gold, Chava Perry, Irit Avivi & Ron Ram

  3. Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

    Ofrat Beyar-Katz, Yael Bar-On, Odelia Amit, Chava Perry, Irit Avivi, Ron Ram & Einat Even-Sapir

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Correspondence to Einat Even-Sapir.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. All included data were collected as part of a retrospective study protocol approved by the local institutional ethics committee, which waived written informed consent (Reference ID 0503–20-TLV).

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Cohen, D., Luttwak, E., Beyar-Katz, O. et al. [18F]FDG PET-CT in patients with DLBCL treated with CAR-T cell therapy: a practical approach of reporting pre- and post-treatment studies. Eur J Nucl Med Mol Imaging 49, 953–962 (2022). https://doi.org/10.1007/s00259-021-05551-5

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