Axi-cel vs chemoimmunotherapy in older patients with R/R LBCL

Older patients with relapsed/refractory (R/R) large B-cell lymphoma (LBCL) have poor outcomes with standard salvage chemotherapy and stem cell transplantation.¹ Additionally, older patients and/or patients with poor Eastern Cooperative Oncology Group Performance Status (ECOG PS) have limited treatment options. Axicabtagene ciloleucel (axi-cel), an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, is approved by the U.S. Food and Drug Administration (FDA) as a second-line treatment for patients with LBCL. A post-hoc analysis from the ZUMA-1 trial (NCT02348216) and a survival analysis from the ZUMA-7 trial (NCT03391466) demonstrated the effectiveness of axi-cel in patients aged ≥65 years with R/R LBCL.¹

Below, we summarize results from an analysis comparing real-world outcomes of axi-cel vs chemoimmunotherapy (CIT) in patients with R/R LBCL after ≥2 lines of therapy, including patients aged ≥65 years and/or had an ECOG PS of 2, published by Lunning et al.¹ in American Journal of Hematology.

Study design and patient population¹

• This analysis compared outcomes of 1,146 patients from the Centre for International Blood and Marrow Transplant Research (CIBMTR) observational database treated with axi-cel vs 469 patients who received CIT from the retrospective SCHOLAR-1 study.
• Endpoints included overall response rate, complete response rate, and overall survival (OS).
• Median follow-up was 24.5 months (95% confidence interval [CI], 24.3–24.9) and 59.8 months (95% CI, 52.3–65.0) in the axi-cel and CIT groups, respectively.

Key findings¹

Patient characteristics

• Before propensity score matching, patients in the axi-cel group were older, more likely to have ECOG PS <2, and were more heavily pretreated (Table 1).
• After propensity score matching:
  • The response rate analysis set included 493 and 289 patients from the axi-cel and CIT groups, respectively.
  • The survival analysis set included 659 and 406 patients from the axi-cel and CIT groups, respectively.

Table 1. Patient characteristics*

Baseline characteristics, % (unless otherwise specified)	Axi-cel (n = 1,146)	CIT (n = 469)
Axi-cel, axicabtagene ciloleucel; CIT, chemoimmunotherapy; ECOG PS, Eastern Cooperative Oncology Group Performance Status. *Adapted from Lunning, et al.1
Median age, years (range)	62.3 (19.6–86.2)	55.4 (19.8–81.2)
<65 years	61	86
≥65 years	39	14
≥70 years	20	6
ECOG PS
0–1	85	63
≥2	4	11
Unknown	11	26
Prior lines of therapy
2	34	96
≥3	66	4

Efficacy

• The estimated 12-month OS rate was 62% (95% CI, 58–66) and 28% (95% CI, 24–33) in the axi-cel and CIT groups, respectively.
• Median OS was longer in axi-cel vs CIT groups, respectively (hazard ratio [HR], 0.30; 95% CI 0.24–0.37) as well as in the subgroups:
  • <65 years: HR, 0.29 (95% CI, 0.22–0.28)
  • ≥65 years: HR, 0.32 (95% CI, 0.22–0.48)
  • ECOG PS <2: HR, 0.27 (95% CI, 0.20–0.35)
  • ECOG PS = 2: HR, 0.72 (95% CI 0.41–1.29).
• The overall response rate and complete response rates were also higher in the axi-cel vs the CIT group (Figure 1).

Axi-cel, axicabtagene ciloleucel; CIT, chemoimmunotherapy; CR, complete response; ECOG PS, Eastern Cooperative Oncology Group performance status; ORR, overall response rate.
*Adapted from Lunning, et al.¹

 

Key learnings
This real-world analysis demonstrated the benefit of axi-cel over CIT in patients with R/R LBCL. The improved response rates were more pronounced in patients aged ≥65 years, suggesting these patients in particular may benefit from axi-cel treatment. These results support the use of axi-cel therapy in older patients and/or patients with a poorer ECOG PS with R/R LBCL.