Predictive Value of Interim and End of Treatment PET/CT in Front-Line Treatment of Peripheral T-Cell Lymphoma

Background: The introduction of PET has consistently changed the management of most lymphomas. In peripheral T-cell lymphomas (PTCL) its use in the staging is recommended, but the predictive role of PET during front-line therapy remains to be determined. The aim of this study is to evaluate the predictive role of PET in first-line treatment of PTCL.

Methods: We retrospectively collected data of adult patients diagnosed with PTCL and actively treated between 2014 and 2024 at the Catalan Institute of Oncology of Barcelona and the Fondazione IRCCS Ca' Granda Ospedale Maggiore of Milan. All patients were evaluated with PET at baseline, interim (iPET) and end of treatment (ePET). We calculated total metabolic tumor volume (TMTV), total lesion glycolysis (TLG) and Deauville score (DS). TMTV and TLG were calculated using the SUV4.

Results: We identified 47 patients with available PET. At diagnosis, median age was 62 years (18-83), 40 (85%) with advance stage, 6 (13%) with ECOG ≥ 2, 26 (55%) with increased LDH, 26 (57%) with IPI 3-5, 20 (47%) with PIT > 1. Histologically, 13 (27%) pts with PTCL-NOS, 22 (47%) with AITL, 7 (15%) with ALK- and 5 (11%) ALK+ ALCL. At baseline PET, median TMTV was 78.63 cm3 (0-4833), median TLG was 540 cm3 (0-54253.78), with higher values in AITL cases.

iPET was performed after 3 cycles in 23 (49%) and after 4 cycles in 22 (47%) pts, with 2 pts evaluated after 2 cycles due to progression. At iPET, 30 (64%) pts were in complete metabolic response (CMR) with Deauville Score (DS) 1-3, 11 (23%) in partial metabolic response (PMR) with DS4 and 6 (12%) with progressive disease with DS5, all of whom switched to 2nd line treatment. Median TMTV at iPET was 0 cm3 (0-183), median TLG was 0 (0-557).

Among the 45 pts evaluated after 3 and 4 cycles, CMR was achieved in 13 (57%) and 17 (77%), respectively (p=0.13). Eight (35%) and 3 (14%) pts were in PMR at iPET after 3 and 4 cycles, respectively. Patients with higher MTV and higher TLG at baseline were more frequently DS4-5 at iPET (p=0.6). Forty (85%) pts experienced a reduction of MTV ≥ 90% (ΔMTV) more frequently with iPET DS1-3 (p=0,02).

Forty-one (91%) patients completed front-line therapy and were evaluated with ePET. CMR was reported in 27 (68%) pts, PMR in 7 (18%) and PD in 6 (15%). Among pts with CMR at iPET, 22 (74%) maintained CMR, 4 (13%) converted to PMR and 4 (13%) progressed. Among pts with PMR at iPET, 6 (55%) converted to CMR, 3 (27%) maintained PMR and 2 (18%) progressed. Eleven pts (24%) were consolidated with autologous stem cell transplantation, all in CMR at ePET, except for 2 pts in PMR.

With a median follow-up of 27 months (2-98), 21 (45%) pts relapsed/progressed. Median progression-free survival (PFS) was 24 months (1-94). According to the iPET, median PFS of DS1-3, DS4 and DS5 were NR, 25 and 2 months, respectively.

In univariate analysis, bone marrow infiltration (0,004), extranodal involvement (p=0,04) and IPI 3-5 (p=0,006) were associated with worse PFS. TMTV value at baseline did not impact significantly on PFS when dichotomized for median TMTV value (mPFS for low baseline MTV was 28 months vs 12 months for high MTV). Instead, iPET impacted on PFS (DS1-3 vs DS4 vs DS5, p=0.001; DS1-3 vs DS4-5, p=0.003), as well as ΔMTV > 90% (p=0,02). No impact of ΔMTV was shown in pts with iPET DS4. In multivariate analysis, only iPET DS maintained its prognostic relevance (for DS1-3 vs DS4 vs DS5: HR 2.9, 95%CI 1,3-6.4).

Median OS was not reached. The estimated 2-year OS was 77% (95%CI, 58-88) with no significant difference according to TMTV at baseline, ΔMTV or DS at iPET.

Conclusions: Our study highlights the potential role of iPET in the management of PTCL. Reaching an early CMR and ΔMTV > 90% seems to be associated with longer PFS. Pts with iPET DS4 remain challenging, since half of them may convert to CMR with the treatment. Further investigations, with larger sample size, are need to better understand the prognostic role of other radiomics features such as TMTV at baseline and ΔMTV in first-line treatment of PTCL.

de Oliveira:Jansen: Consultancy; Abbie: Consultancy; AstraZeneca: Consultancy. Gonzalez Barca:Abbvie: Consultancy, Other: Travel funding, Speakers Bureau; EUSAPharma: Consultancy, Other: Travel funding, Speakers Bureau; AstraZeneca: Speakers Bureau; Beigene: Consultancy; Novartis: Consultancy; Takeda: Speakers Bureau; Roche: Speakers Bureau; Incyte: Consultancy, Speakers Bureau; Lilly: Consultancy; Janssen: Consultancy, Other: Travel funding, Speakers Bureau; Kiowa: Consultancy, Speakers Bureau; Gilead: Consultancy. Rossi:Takeda: Membership on an entity's Board of Directors or advisory committees; Jansen: Membership on an entity's Board of Directors or advisory committees; Incyte: Membership on an entity's Board of Directors or advisory committees. Sureda Balari:Sanofi: Consultancy; Gilead: Consultancy; Janssen: Consultancy; Novartis: Consultancy; BMS/Celgene: Consultancy; Takeda: Consultancy. Domingo Domenech:Takeda: Consultancy, Honoraria; Beigene, Kyowa Kirin: Consultancy.