Real-world comparison of lisocabtagene maraleucel and axicabtagene ciloleucel in large B-cell lymphoma: an inverse probability of treatment weighting analysis with 3-year follow-up

Abstract

Lisocabtagene maraleucel (liso-cel) and axicabtagene ciloleucel (axi-cel) are Food and Drug Administration- and European Medicines Agency-approved chimeric antigen receptor (CAR) T-cell therapies for relapsed/refractory large B-cell lymphoma (LBCL). However, comparative real-world analyses of their efficacy and toxicity with extended follow-up are lacking. We conducted a retrospective study of 160 LBCL patients treated at the Fred Hutchinson Cancer Center with commercial liso- cel or axi-cel per standard of care. Using inverse probability of treatment weighting (IPTW) to mitigate treatment allocation bias and multivariable adjustments to minimize other sources of confounding, we assessed the impact of CAR T-cell product type on outcomes. Axi-cel was associated with significantly higher rates of cytokine release syndrome (CRS; grade [G]1+: adjusted odds ratio [aOR] =4.27; P=0.004; G2+: aOR=2.88; P=0.006), immune effector cell-associated neurotoxicity syndrome (ICANS; G1+: aOR=2.10; P=0.048), and immune effector cell-associated hematotoxicity (ICAHT; G1+: aOR=8.09; P<0.001; G2+: aOR=3.86; P=0.001). Axi-cel was also associated with more frequent use of supportive care measures, such as tocilizumab (aOR=2.50; P=0.017), dexamethasone (aOR=2.77; P=0.007), and cefepime (aOR=3.37; P=0.001). We could not confirm statistically significant differences in the response rates and survival outcomes after liso-cel versus axi-cel (complete response: aOR=1.12; P=0.8; overall survival: adjusted hazard ratio [aHR] =1.34; P=0.3; progression-free survival: aHR=0.97; P=0.9; duration of response: aHR=0.89; P=0.7; cumulative incidence of relapse: aHR=0.92; P=0.8). In summary, although axicel was associated with greater toxicity requiring more intensive management, the response rates and survival outcomes were comparable between axi-cel and liso-cel.

Figure 1.

Comparative analysis of toxicities between CAR T-cell product types. (A) Inverse probability of treatment weighting (IPTW) and (B) unweighted comparisons of cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and early immune effector cell-associated hematotoxicity (ICAHT). Weighted patient numbers have been rounded to the nearest integer. P values for comparisons of toxicities were derived from the χ test or Fisher’s exact test (with Rao and Scott’s second-order correction for IPTW comparisons). CAR: chimeric antigen receptor; axi-cel: axicabtagene ciloleucel; liso-cel: lisocabtagene maraleucel.

Figure 2.

Analysis of survival outcomes and non-relapse mortality. Inverse probability of treatment weighting Kaplan-Meier plots, stratified by product type, showing (A) overall survival, (B) progression-free survival, (C) duration of response, and (D) cumulative incidence of relapse, and non-relapse mortality (NRM). Median survival times were analyzed using weighted univariate Cox regression, and the 1-year cumulative incidence of relapse was assessed with Gray’s test. axi-cel: axicabtagene ciloleucel; liso-cel: lisocabtagene maraleucel; NA: not applicable.

Figure 3.

Kaplan-Meier analysis of overall survival in patient subgroups. Inverse probability of treatment weighting Kaplan-Meier plots depicting overall survival of patients with (A) bulky disease (largest lesion diameter ≥5 cm), (B) high lactate dehydrogenase (LDH) (≥210 U/L), (C) extranodal involvement, and (D) who received bridging therapy. P values were derived from weighted univariate Cox regressio to axi-cel: axicabtagene ciloleucel; liso-cel: lisocabtagene maraleucel.

Figure 4.

Kaplan-Meier analysis of progression-free survival in patient subgroups. Inverse probability of treatment weighting Kaplan-Meier plots depicting progression-free survival of patients with (A) bulky disease (largest lesion diameter ≥5 cm), (B) high lactate dehydrogenase (LDH) (≥210 U/L), (C) extranodal involvement, and (D) who received bridging therapy. P values were derived from weighted univariate Cox regression. axi-cel: axicabtagene ciloleucel; liso-cel: lisocabtagene maraleucel.

Figure 5.

Sensitivity analyses of response, survival, and toxicity outcomes. Sensitivity analyses evaluating: (A) complete response (CR), (B) duration of response (DOR), (C) relapse rate, (D) progression-free survival (PFS), (E) overall survival (OS), (F) cytokine release syndrome (CRS) grade 1 (G1) or higher, (G) CRS grade 2 or higher, (H) immune effector cell-associated neurotoxicity syndrome (ICANS) G1 or higher, (I) early immune effector cell-associated hematotoxicity (ICAHT) G1 or higher, and (J) early ICAHT G2 or higher. Three inverse probability of treatment weighting models were compared: the original model, Sensitivity #1 (restricted to patients treated from April 2021 onwards), Sensitivity #2 (incorporating day 0 ferritin and CRP values), and Sensitivity #3 (incorporating the maximum standardized uptake value from pre-CAR T positron emission tomography/computed tomography scans). Adjusted hazard ratios (HR) or odds ratios (OR) are displayed with 95% confidence intervals. Statistical significance is denoted as *P<0.05; **P<0.01; ***P<0.001. CAR: chimeric antigen receptor. axi-cel: axicabtagene ciloleucel; liso-cel: lisocabtagene maraleucel.