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Clinical Trial
. 2022 Feb 22;6(4):1255-1263.
doi: 10.1182/bloodadvances.2021005385.

Pretherapy metabolic tumor volume is associated with response to CD30 CAR T cells in Hodgkin lymphoma

Timothy J Voorhees  1   2 , Beibo Zhao  3 , Jorge Oldan  4 , George Hucks  1   5 , Amir Khandani  4 , Christopher Dittus  1   2 , Jennifer Smith  3 , J Kaitlin Morrison  1 , Catherine J Cheng  1 , Anastasia Ivanova  1 , Steven Park  6 , Thomas C Shea  1   2 , Anne W Beaven  1   2 , Gianpietro Dotti  1 , Jonathan Serody  1   2 , Barbara Savoldo  1   5 , Natalie Grover  1   2
Affiliations
Clinical Trial

Pretherapy metabolic tumor volume is associated with response to CD30 CAR T cells in Hodgkin lymphoma

Timothy J Voorhees et al. Blood Adv. .

Abstract

Our group has recently demonstrated that chimeric antigen receptor T-cell therapy targeting the CD30 antigen (CD30.CAR-T) is highly effective in patients with relapsed and refractory (r/r) classical Hodgkin lymphoma (cHL). Despite high rates of clinical response, relapses and progression were observed in a subset of patients. The objective of this study was to characterize clinical and correlative factors associated with progression-free survival (PFS) after CD30.CAR-T cell therapy. We evaluated correlatives in 27 patients with r/r cHL treated with lymphodepletion and CD30.CAR-T cells. With a median follow-up of 9.5 months, 17 patients (63%) progressed, with a median PFS of 352 days (95% confidence interval: 116-not reached), and 2 patients died (7%) with a median overall survival of not reached. High metabolic tumor volume (MTV, >60 mL) immediately before lymphodepletion and CD30.CAR-T cell infusion was associated with inferior PFS (log rank, P = .02), which persisted after adjusting for lymphodepletion and CAR-T dose (log rank, P = .01 and P = .006, respectively). In contrast, receiving bridging therapy, response to bridging therapy, CD30.CAR-T expansion/persistence, and percentage of CD3+PD-1+ lymphocytes over the first 6 weeks of therapy were not associated with differences in PFS. In summary, this study reports an association between high baseline MTV immediately before lymphodepletion and CD30.CAR-T cell infusion and worse PFS in patients with r/r cHL. This trial was registered at www.clinicaltrials.gov as #NCT02690545.

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Figures

None
Graphical abstract
Figure 1.
Figure 1.
Axial fused, coronal PET-only, and maximum intensity projection images. Representative lesion segmented using 41% of SUVmax as cutoff (blue arrows).
Figure 2.
Figure 2.
Cohort survival. PFS (A) and OS (B) for all patients treated with CD30.CAR-T cell therapy.
Figure 3.
Figure 3.
PFS by baseline MTV. (A) PFS by high (blue) vs low (red) MTV, using a cutoff of 60 mL. (B) PFS by change to MTV with bridging therapy using a cutoff of 60 mL. Low MTV to low MTV (red), high MTV to low MTV (blue), and high MTV to high MTV (light green). *Pairwise P value low to low MTV compared with high to high MTV.
See this image and copyright information in PMC

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