Interim PET after 4 Cycles Predicts Outcome in Histomolecularly Confirmed Primary Mediastinal B-Cell Lymphoma.

Camus, Vincent;Molina, Thierry Jo;Desmots, Fabienne;Blanc-Durand, Paul;Fest, Thierry;et.al.
(2025) Blood Advances — Vol. 9, n° 9, p. 2232-2246 (2025)

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  • Camus, Vincentorcid-logo
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  • Molina, Thierry Jo
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  • Desmots, Fabienneorcid-logo
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  • Blanc-Durand, Paul
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  • Fest, Thierryorcid-logo
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Abstract
(en) The GAINED study (NCT01659099) was a randomized phase 3 trial comparing obinutuzumab (G) to rituximab (R) plus ACVBP or CHOP14 induction, followed by PET-guided consolidation. This post-hoc analysis aimed to detail the outcomes of primary mediastinal B-cell lymphoma (PMBL) patients, verified through expert pathological review and the use of gene-expression profiling (GEP) and Next-Generation sequencing. Of the centrally reviewed 620 patients, 138 (22.3%) confirmed PMBL cases were analyzed. Baseline characteristics included a median age of 33.5 years, 63.8% female, 55.1% stage III-IV, 90.6% elevated LDH, 87.6% ECOG 0-1, 62.3% extranodal involvement, 52.6% aaIPI 2-3, and 53.6% Bulk (>10cm). Induction regimens were R/G-CHOP14 (56.9%) and R/G-ACVBP (43.1%). Post-induction treatments, based on interim PET (iPET) results, included: standard consolidation chemotherapy (59.8%) if ΔSUVmax >66% after cycle 2 and >70% after cycle 4 (PET2-/4-), intensive treatment and autologous transplantation (26.8%) if PET2+/4-, and salvage therapy (13.4%) if PET4+ (ΔSUVmax ≤70%). Among patients with GEP data (n=107), 38 (35.5%) were PDL1high/PDL2high. Key somatic mutations data (n=87) included SOCS1 (70.1%), B2M (56.3%), STAT6 (49.4%), TNFAIP3 (47.1%), GNA13 (39.1%), CIITA (37.9%), CD58 (36.8%), and TP53 (29.9%). After a median follow-up of 39.5 months, 2-year PFS and OS rates were 86.2% and 93.2%, respectively. In a multivariate model including Bulk, aaIPI, and ΔSUVmax PET2/PET4, only Bulk and ΔSUVmax PET4 ≤70% were associated with shorter PFS (HR 4.39 [1.28-15.11] and 4.95 [1.71-14.3], respectively), while none were associated with OS. The ΔSUVmax-based interim PET4 response emerged as the strongest predictor of patient outcomes in this selected clinical trial population.
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Camus, V., Molina, T. J., Desmots, F., Blanc-Durand, P., Kanoun, S., Moslemi, A., Ruminy, P., Le Gouill, S., Ghesquieres, H., Obéric, L., Morschhauser, F., Tilly, H., Ribrag, V., Houot, R., Thieblemont, C., Maisonneuve, H. G., Claves, F., Bouabdallah, K., Haioun, C., et al. (2025). Interim PET after 4 Cycles Predicts Outcome in Histomolecularly Confirmed Primary Mediastinal B-Cell Lymphoma. Blood Advances, 9(9), 2232-2246. https://doi.org/10.1182/bloodadvances.2024015577 (Original work published 2025)