Network meta-analysis of CAR T-Cell therapy for the treatment of 3L+ R/R LBCL after using published comparative studies

Figures & data

Figure 1. Study selection flow diagram.

Figure 2. Network of evidence for (a) the primary evidence base; and (b) the extended evidence base.

Axi-cel, axicabtagene ciloleucel; IPI, international prognostic index; liso-cel, lisocabtagene maraleucel; MAIC, matching-adjusted indirect comparison; SoC, standard of care, tisa-cel; tisagenlecleucel.

Table 1. Adjustment methods and details in the primary network.

	Axi-cel (IPD) vs salvage CT (IPD)	Liso-cel (IPD) vs salvage CT (summary data)	Tisa-cel (IPD) vs salvage CT (IPD)
Variables included in adjustments
Sex	Yes	Yes
Lines of therapy	Yes	–
NHL subtype	Yes	Yes	Restriction
IPI	Sensitivity only	Yes
Age	Yes	Yes	Yes
Disease stage	Sensitivity only	Yes	Yes
ECOG	–	–	Restricted
LDH	–	–	–
Extranodal site involvement	–	–	–
SCT
Prior ASCT	Yes	Yes	Yes
Prior allogeneic SCT	–	–	Restricted
Relapse within 12 months of ASCT	Yes	–	–
Post-treatment SCT ^†	Yes	–	–
R/R to last LoT	–	Yes	Yes
Refractory to ≥ 2 consecutive LoT	Yes	–
Primary refractory	Yes	–	–
Status of disease	–	–	Yes
Number of relapses	–	–	Yes
Patients didn’t receive rituximab at 2^nd LoT	–	–	Restricted
Time to second LoT	–	–	Yes
CNS involvement	–	–	Restricted
Sample sizes
CAR T-cell	80–81	ESS:142	11–143
Standard of Care	ESS: 331–340^‡	523–603	ESS:205^‡

ASCT, autologous stem cell transplant; axi-cel, axicabtagene ciloleucel; CAR, chimeric antigen receptor; CNS, central nervous system; CT, chemotherapy; ECOG, Eastern Cooperative Oncology Group; ESS, effective sample size; IPD, individual patient data; IPI, international prognostic index; LDH, lactate dehydrogenase; liso-cel, lisocabtagene maraleucel; LoT, line of therapy; NHL, non-Hodgkin lymphoma; PMBCL, primary mediastinal B-cell lymphoma; R/R, relapsed/refractory; SCT, stem-cell transplantation; tisa-cel; tisagenlecleucel. †While other variables are included in the derivation of weights, this one is included in the model itself as a time-varying predictor. ‡Sum of standardized mortality ratio weights.

Table 2. Network meta-analysis results using the primary network.

	OS (HR, 95% CrI)	ORR (OR, 95% CrI)	CR (OR, 95% CrI)
Compared to salvage CT:
Axi-cel vs salvage CT	0.27 (0.19, 0.38)	9.29 (5.18, 18.16)	8.57 (4.95, 15.00)
Liso-cel vs salvage CT	0.50 (0.40, 0.60)	7.06 (4.71, 10.73)	12.89 (8.06, 20.87)
Tisa-cel vs salvage CT	0.57 (0.44, 0.73)	1.66 (1.05, 2.61)	–
Between CAR T-cell therapy comparison:
Axi-cel vs liso-cel	0.54 (0.37, 0.79)	1.32 (0.64, 2.89)	0.67 (0.32, 1.39)
Axi-cel vs tisa-cel	0.47 (0.26, 0.88)	5.63 (2.66, 12.54)	–
Liso-cel vs tisa-cel	0.87 (0.42, 1.78)	4.26 (2.33, 7.93)	–

Axi-cel, axicabtagene ciloleucel; CAR T-cell therapy, chimeric antigen receptor T-cell therapy; CrI, credible interval; CR, complete response; CT, chemotherapy; liso-cel, lisocabtagene maraleucel; ORR, overall response rate; OS, overall survival; SoC, standard of care; tisa-cel; tisagenlecleucel.

Table 3. Comparison of the three CAR T-cell treatments – NMAs vs published ITC results.

	Network	Axi-cel vs Liso-cel	Axi-cel vs Tisa-cel	Liso-cel vs Tisa-cel
Overall survival (HR)	ITC	0.53 (0.34–0.82) [32] 1.23 (0.67–2.27) [14]	0.51 (0.31–0.83) [31]	0.89 (0.49–1.61) [29] 0.67 (0.47–0.95) [33]
	NMA	0.54 (0.37, 0.79)	0.47 (0.26, 0.88)	0.87 (0.42, 1.78)
Overall response rate (OR)	ITC	2.18 (0.96–4.98) [32] 0.71 (0.29–1.79) [14]	4.77 (1.90–12.01) [31]	2.78 (1.63–4.74) [33]
	NMA	1.32 (0.64, 2.87)	5.62 (2.64, 12.42)	4.24 (2.28, 7.91)
Complete response (OR)	ITC	1.84 (0.97–3.50) [32] 0.83 (0.38–1.79) [14]	2.65 (1.26–5.58) [31]	2.01 (1.22–3.30) [33]
	NMA	0.67 (0.32, 1.37)	–	–

ITC results are from published matching-adjusted indirect comparisons, anchored results are from the NMA we conducted. IPD was used for axi-cel in two studies [15]; 95% CI’s were used in the published ITC studies, and 95% CrI’s were used in the NMA comparisons and; IPD was used for liso-cel in two studies [14,43]; IPD was used for tisa-cel in one study [44]; otherwise summary level data was used. Note that for axi-cel vs liso-cel, the primary analysis did not include liso-cel patients who had received bridging therapy.

Axi-cel, axicabtagene ciloleucel; CI, confidence interval; CrI, credible interval; HR, hazard ratio; ITC, indirect treatment comparison; liso-cel, lisocabtagene ciloleucel; NMA, network meta-analysis; OR, odds ratio; tisa-cel, tisagenlecleucel.

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