Comparative analysis of tabelecleucel and current treatment in patients with Epstein-Barr virus-positive post-transplant lymphoproliferative disease following hematopoietic cell transplant or solid organ transplant

Figures & data

Table 1. Demographic and baseline characteristics.

Characteristic	Study RS002 (N = 84)	ALLELE (N = 30)
Age at index date^Table Footnotea (years)
Median (IQR)	44.1 (26.4, 58.6)	41.8 (24.0, 65.1)
Min, Max	3.1, 73.6	3.2, 81.5
Female, n (%)	27 (32.1)	15 (50.0)
Extranodal sites of PTLD, n (%)	56 (66.7)	22 (73.3)
Early PTLD onset,^Table Footnoteb n (%)	44 (52.4)	12 (40.0)
Response to initial rituximab treatment, n (%)
Responders (CR + PR)	24 (28.6)	10 (33.3)
Non-responders (SD + PD)	60 (71.4)	19 (63.3)
UK	0	1 (3.3)
Number of prior therapies, n (%)
1	55 (65.5)	16 (53.3)
≥2	29 (34.5)	14 (46.7)

CR, Complete response; HCT, Hematopoietic cell transplant; IQR, Interquartile range; Max, Maximum; Min, Minimum; PD, Progressive disease; PR, Partial response; PTLD, Post-transplant lymphoproliferative disease; SOT, Solid organ transplant; SD, Stable disease.

^a Defined as the date of the first dose of tabelecleucel for patients in ALLELE and the start of the next line of systemic therapy for patients in Study RS002.

^b Defined according to the time from transplant to PTLD diagnosis: early onset (late onset) was defined as ≤100 (>100) days for HCT patients and ≤2 (>2) years for SOT patients.

Table 2. Time-related variables.

Time-Related Variable	Study RS002 (N = 84)	ALLELE (N = 30)
Transplant to PTLD diagnosis, months
Median (IQR)	6.5 (3.0, 79.2)	7.4 (3.8, 66.9)
Min, Max	0.9, 334.5	0.6, 282.5
PTLD diagnosis to R/R date, months
Median (IQR)	3.1 (0.8, 8.2)	2.0 (0.9, 3.6)
Min, Max	0.0,^Table Footnotea 87.5	0.0,^Table Footnotea 189.6
PTLD diagnosis to index date,^Table Footnoteb months
Median (IQR)	3.6 (1.1, 9.6)	3.6 (2.0, 13.0)
Min, Max	0.0, 90.0	0.7, 190.5

HCT, Hematopoietic cell transplant; IQR, Interquartile range; Max, Maximum; Min, Minimum; PTLD, Post-transplant lymphoproliferative disease; R/R, Relapsed/refractory.

^a A prior initiation of rituximab in the HCT setting before PTLD diagnosis by biopsy.

^b Defined as first dose of tabelecleucel for patients in ALLELE and the start of the next line of systemic therapy for patients in Study RS002.

Figure 1. Boxplot of the estimated conditional probability of receiving treatment between the treatment arm and the external comparator arm. The PS overlapped for 81.6% of the total patients included in the analysis. The edges of the box indicate the IQR, values between Q1 and Q3. The diamond indicates the mean, the line inside the box indicates the median. The whiskers represent the minimum and maximum observations within a range from Q1 − 1.5*IQR to Q3 + 1.5*IQR.

Study RS002: estimated conditional probability of being treated: mean = 0.241; median = 0.221; IQR = 0.119, 0.340; minimum, maximum = 0.023, 0.639.

ALLELE: estimated conditional probability of being treated: mean = 0.383; median = 0.369; IQR = 0.271, 0.504; minimum, maximum = 0.117, 0.697.

IQR, Interquartile range; PS, Performance score; Q, Quartile.

Table 3. Comparison of baseline covariates before and after weighting.

Covariate	Standardized Mean Difference
	Unadjusted	SMRW
Age risk
High (≥60 years) vs. low (<60 years)	0.382	−0.090
LDH risk
High (≥250 U/L) vs. low (<250 U/L)	0.374	0.001
Missing vs. low (<250 U/L)	−0.681	−0.002
Sex
Female vs. male	0.369	−0.021
Early onset of PTLD
Yes vs. no	−0.250	0.019
Transplant type
HCT vs. SOT	0.077	−0.063
Extranodal sites of PTLD
Yes vs. no	0.146	−0.039
Number of lines of prior therapies
≥2 vs. 1	0.249	0.034
Time from PTLD diagnosis to R/R	0.124	0.088

HCT, Hematopoietic cell transplant; LDH, Lactate dehydrogenase; PTLD, Post-transplant lymphoproliferative disease; R/R, Relapsed/refractory; SMRW, Standardized mortality ratio weighting; SOT, Solid organ transplant.

Figure 2. Kaplan-Meier survival estimates between the treatment arm and the external comparator arm (unadjusted). Patients who received tabelecleucel had significantly longer overall survival than patients who received current treatment. The index date is defined as the date of the first dose of tabelecleucel in ALLELE and the date of the next line of systemic therapy in RS002.

Figure 3. Kaplan-Meier survival estimates between the treatment arm and the external comparator arm (adjusted: standardized mortality ratio weighting). Patients who received tabelecleucel had significantly longer overall survival than patients who received current treatment. The index date is defined as the date of the first dose of tabelecleucel in ALLELE and the date of the next line of systemic therapy in RS002.

Table 4. OS between the treatment arm and the external comparator arm.

	Study RS002 (N = 84)	ALLELE (N = 30)
Survival status, n (%)
Died	58 (69.0)	11 (36.7)
Censored	26 (31.0)	19 (63.3)
OS (Kaplan-Meier), months
Median (95% CI), unadjusted	5.4 (2.5, 12.4)	NE (11.0, NE)
Median (95% CI), SMRW adjusted	3.3 (2.0, 8.0)	NE (11.0, NE)
OS benefit of tabelecleucel (ALLELE vs. Study RS002)
Model^Table Footnotea	HR (95% CI)	P-value
Unadjusted	0.47 (0.25, 0.88)	0.018
SMRW, adjusted^Table Footnoteb	0.37 (0.20, 0.71)	0.003

CI, Confidence interval; HR, Hazard ratio; NE, Not estimable; OS, Overall survival; SMRW, Standardized mortality ratio weighting.

^a All the models were constructed by using Cox proportional hazards regression model with robust sandwich variance estimate.

^b Weighted sample size (treatment vs. control): 30.0 vs. 29.3.

Figure 4. Kaplan-Meier survival estimates between the treatment arm and the external comparator arm (unadjusted). Patients who received tabelecleucel had significantly longer overall survival than patients who received current treatment. The index date is defined as the date of the first dose of tabelecleucel in ALLELE and the date that disease was relapsed/refractory to rituximab ± chemotherapy in RS002.

Figure 5. Kaplan-Meier survival estimates between the treatment arm and the external comparator arm (adjusted: standardized mortality ratio weighting). Patients who received tabelecleucel had significantly longer overall survival than patients who received current treatment. The index date is defined as the date of the first dose of tabelecleucel in ALLELE and the date that disease was relapsed/refractory to rituximab ± chemotherapy in RS002.