Real-World Interim PET/CT Scan Use during Frontline (1L) Therapy and Subsequent Treatment Characteristics in Patients with Refractory Diffuse Large B-Cell Lymphoma (DLBCL)
Authors: Reshef Ran , Lau Constance , Hsu Hil , Doble Brett , Spooner Clare , Patel Anik R , Nikolaenko Liana 
Published: December 2024

Introduction
Response assessment with interim PET/CT (iPET) in 1L treatment (tx) is in NCCN guidelines for DLBCL and becoming US standard of care. iPET was recently added to UK guidelines and is established practice in France. iPET is used as an indicator of response to tx and prognosis and may support earlier decision-making for tx intensification or switch to second-line (2L) tx. iPET may be pertinent to CAR-T tx given that early planning facilitates prompt tx, especially in high-risk cases. However, iPET use and subsequent tx are not well-characterized in the US. The purpose of this study is to describe real-world 1L iPET use for US patients (pts) presumed refractory after 1L and characteristics of subsequent tx.
Methods
This is a retrospective real-world study of data from 01/2017-12/2023 in a US database of administrative health claims for members of large commercial and Medicare Advantage health plans. All adult (18+ years) pts with available demographic characteristics, evidence of DLBCL diagnosis with 12+ months of prior continuous enrollment, and 2+ cycles of 1L R-CHOP or R-EPOCH were included; 1L must have initiated 150+ days before data cutoff to allow the potential for 6+ cycles. Descriptive statistics summarized available pt/clinical characteristics, tx, and iPET use with continuous variables as medians (interquartile range [IQR]).
iPET was defined as a scan between start of Cycle 2 and 5 in 1L (or for pts with 4 or fewer cycles, within 60 days from last 1L cycle start). Duration of 1L was time from 1L start to last cycle start without adding time for clinical benefit. Subgroup analyses were performed in pts who received 2L tx within 120 days after the last 1L R-CHOP cycle start as a proxy for presumed-refractory disease since PET/CT scan results were unavailable. The results were stratified by iPET/no iPET and by total 1L cycles received suggesting early switch (2-4 cycles)/standard switch (5 or more cycles) to 2L. Tx-free interval (TFI) was time from last 1L cycle start to 2L start and time-to-next tx (TTNT) was time from 1L start to 2L start.
Results
In total, 5,916 pts were included with a median age of 73 years (66, 79). Pts were mostly White (76%), Male (55%), and Medicare insured (77%). Approximately half (53%) of pts had no NCI-defined comorbidities, and 919 (16%) pts had two or more. Follow-up time from 1L start was 20 months (9, 39). Of this 1L cohort, nearly all (96%) received R-CHOP (median: 5 cycles [4, 6]) with a median time from 1L start to last 1L cycle start of 105 days (70, 107). Almost two-thirds of pts (63%) received iPET (62% in 2017-21 & 67% in 2022-23). Baseline characteristics in pts who received iPET were largely similar to no iPET pts. Time from 1L start to iPET was 60 days (52, 76). Approximately half (48%) of iPET occurred between start of Cycle 3 and 4, with the rest split between start of Cycle 2 and 3 (26%) and start of Cycle 4 and 5 (26%).
A subset of 265 pts who received 1L R-CHOP (R-EPOCH not assessed due to sample size) had presumed-refractory disease; 184 (69%) had iPET. The most common regimen class received in 2L was chemo-immunotherapy in pts with iPET (64%) and without iPET (67%); CAR-T was used in 15 pts (8.2%) with iPET, and in 2 (2.5%) without iPET.
Among presumed-refractory pts with iPET, early switch pts (n=79) had a TFI of 47 days (41, 59) and TTNT of 118 days (101, 128); standard switch pts (n=105) had a TFI of 67 days (58, 77) and TTNT of 174 days (162, 183). In pts without iPET, early switch pts (n=24) had a TFI of 29 days (22, 51) and TTNT of 68 days (62, 84); standard switch pts (n=57) had a TFI of 63 days (47, 75) and TTNT of 168 days (157, 187).
Conclusions
These data suggest iPET use is common in US pts with DLBCL. In presumed-refractory pts who received 2L, early switch after iPET had shorter TFI/TTNT than pts with standard switch. The smallest group were early switchers without iPET who yielded the shortest TFI/TTNT, consistent with a subpopulation that experiences clear early tx failure (e.g., symptomatic progression) or is identified via other methods (e.g., interim CT scan). In pts with or without iPET who ultimately had standard switch, the question remains if these pts would benefit from earlier referral to 2L CAR-T given their 1L therapy subsequently failed. Most data were prior to the approval of 2L CAR-T in 2022, potentially understating the role of iPET in earlier referral to a novel, beneficial tx option. Interpretation is however limited without iPET results and additional clinical data, warranting further study.