KEY TAKEAWAYS
- ZUMA-7 (NCT03391466) demonstrated that axi-cel was superior to SOC across common prognostic subgroups, including TB, calculated by the SPD, and LDH.
- MTV, a measure of TB obtained from whole-body FDG PET scans, was positively associated with SPD and LDH in R/R LBCL patients.
- High MTV was associated with superior outcomes in patients treated with axi-cel versus SOC in ZUMA-7, suggesting that MTV is a more accurate and sensitive measure of TB versus SPD.
- Rates of Grade ≥3 neurologic events (NEs) and cytokine release syndrome (CRS) were associated with higher MTV in axi-cel patients, indicating the potential impact of TB on safety outcomes.
- Axi-cel was superior to SOC irrespective of MTV subgroup, highlighting the overall efficacy of the treatment in R/R LBCL patients.
Tumor burden (TB), as measured by the sum of product diameters (SPD), and lactate dehydrogenase (LDH) were two examples of common prognostic groupings where axi-cel outperformed SOC in the ZUMA-7 (NCT03391466) trial (LDH; Locke et al. ASCO 2022. Abstract 7565). Clinical effects of third-line chimeric antigen receptor T-cell treatment for relapsed/refractory (R/R) large B-cell lymphoma have corresponded with MTV measurements of TB (LBCL; Hong et al. Front Oncol. 2021 and Dean et al. Blood Adv. 2020). In this article, we share the clinical results from ZUMA-7 by MTV.
Attenuation-corrected whole-body FDG PET scans were used to determine MTV. A predetermined, semi-automated method assigned whole volumes of interest to tumors. After that, tweaks based on radiologist judgment were implemented. To determine a patient’s MTV, we counted the number of voxels (volumetric pixels) with standardized uptake value (SUV) readings between 41% and 100% of tumor SUVmax and reported the result as MTVtotal (mL). Descriptive statistics (significant at P< .05) were used to analyze the connections between variables. The final tally after assessing 341 patients for MTV: (axi-cel: 176 and SOC: 165). For patients with axi-cel, the median MTV was 228.1 mL (range, 2.3-16,669.3), for those with SOC, it was 231.9 mL (range, 0.04-2811.2), and for all patients, it was 230.2 mL (range, 0.04-16,669.3). Those who had LDH levels that were above the median (n=185) had a greater median MTV than those whose LDH levels were within the normal range (n=156) (371.2 mL [range, 2.3-16,669.3] versus 123.9 mL [range, 0-3712.8]). The Spearman correlation between SPD and MTV was 0.523 (n=308), and between SPD and LDH (n=341) was 0.452 (P.05). With both low (median) and high (>median) MTV, Axi-cel EFS was better than SOC (hazard ratio [HR], 0.423 and HR, 0.417, respectively). High MTV was associated with decreased EFS in Axi-cel and SOC patients (HR, 1.441), but the difference was not statistically significant (HR, 1.486; Figure).
Patients receiving axi-cel who had Grade 3 neurologic episodes (NEs; n=36) had a greater median MTV (320.9 mL [range, 24.3-13,527.0]) than those who had Grade 1-2 NEs or no NEs (n=134; 193.9 [range, 2.3-16,669.3]). Patients receiving axi-cel who experienced Grade 3 cytokine release syndrome (CRS; n=11) had a greater median MTV (582.9 mL [range, 114.6-2508.6]) than those who experienced Grade 1-2 CRS or no CRS (n=159; 203.3 [range, 2.3-16,669.3]). They conclude this is the first meta-analysis to focus on MTV in a prospective R/R LBCL study of this size. Higher MTV was linked with better outcomes in patients treated with axi-cel compared to SOC, similar to the relationships with SPD and LDH previously identified in second-line LBCL (Locke et al. ASCO 2022. Abstract 7565). High MTV was related to poorer outcomes with axi-cel compared to low MTV, and Grade 3 NEs and CRS rates was associated with higher MTV in ZUMA-7 (Locke et al. ASCO 2022. Abstract 7565). However, tumor burden per SPD did not appear to affect axi-cel outcomes. This indicates that MTV is a more precise and sensitive indicator of TB compared to SPD. Nonetheless, even among patients in the high MTV subgroup, axi-cel was better than SOC.
Source: https://cart2023.abstractserver.com/program/#/details/presentations/87
Clinical trial: https://clinicaltrials.gov/ct2/show/NCT03391466/
M.J. Kersten1, F.L. Locke2, O.O. Oluwole3, J. Kuruvilla4, C. Thieblemont5, F. Morschhauser6, G. Salles7, S.P. Rowe8, S. Vardhanabhuti9, S. Filosto9, C. To9, P. Cheng9, M. Schupp9, R. Korn. BA02-1 Association of MTV and Clinical Outcomes in R/R LBCL (ZUMA-7). cart2023.abstractserver.com. (n.d.). CART 2023. [online] Available at: https://cart2023.abstractserver.com/program/#/details/presentations/87 [Accessed 23 Feb. 2023].
