A COMPARISON OF CLINICAL OUTCOMES FROM ZUMA-5 (AXICABTAGENE CILOLEUCEL) AND THE INTERNATIONAL SCHOLAR-5 EXTERNAL CONTROL COHORT IN RELAPSED/REFRACTORY FOLLICULAR LYMPHOMA (R/R FL)
Author(s): ,
Paola Ghione
Affiliations:
Roswell Park Comprehensive Cancer Center,Buffalo,United States;Memorial Sloan Kettering Cancer Center,New York,United States
,
Anik Patel
Affiliations:
Kite, A Gilead Company,Santa Monica,United States
,
Sabela Bobillo
Affiliations:
Vall D’Hebron Insitute of Oncology,Barcelona,Spain
,
Kevin Deighton
Affiliations:
Delta Hat,Nottingham,United Kingdom
,
Caron Jacobson
Affiliations:
Dana-Farber Cancer Institute,Boston,United States
,
Myrna Nahas
Affiliations:
Kite, A Gilead Company,Santa Monica,United States
,
Anthony Hatswell
Affiliations:
Delta Hat,Nottingham,United Kingdom;Department of Statistical Science,University College London,London,United Kingdom
,
Steve Kanters
Affiliations:
RainCity Analytics,Vancouver,Canada
,
Julia Thornton Snider
Affiliations:
Kite, A Gilead Company,Santa Monica,United Kingdom
,
Sattva Neelapu
Affiliations:
The University of Texas MD Anderson Cancer Center,Houston,United States
,
Hervé Ghesquieres
Affiliations:
Centre Hospitalier Lyon Sud,Lyon,France
,
Lia Palomba
Affiliations:
Memorial Sloan Kettering Cancer Center,New York,United States
,
John Radford
Affiliations:
Cancer Research UK,Barts Centre,London,United Kingdom
John Gribben
Affiliations:
The Christie NHS Foundation Trust and University of Manchester,Manchester,United Kingdom
EHA Library. Gribben J. 06/12/21; 330174; LB1904
Prof. John Gribben
Prof. John Gribben
Contributions
Abstract
Presentation during EHA2021: The Late-Breaking Oral Session will be held on Saturday, June 12, 2021 (16:00 - 17:30 CEST) and will be accessible for on-demand viewing until August 15, 2021 on the Virtual Congress platform.

Abstract: LB1904

Type: Oral Presentation

Session title: Late-Breaking Oral Session

Background
In the pivotal ZUMA-5 (Z-5) trial, axicabtagene ciloleucel (axi-cel; an autologous anti-CD19 chimeric antigen receptor T-cell therapy) demonstrated high rates of durable response in r/r FL patients, including those with high-risk disease such as patients who progressed within 24 months of initiating first-line chemoimmunotherapy (POD24).

Aims
To compare clinical outcomes from updated 18-month Z-5 to a matched sample from the international SCHOLAR-5 (S-5) external control cohort.

Methods
The international S-5 cohort source data were extracted for r/r FL patients from 7 institutions in 5 countries who initiated a third or higher (3L+) line of therapy (LOT) after July 2014. Data from the pivotal idelalisib DELTA trial was also included in the S-5 cohort. Z-5 trial eligibility criteria were applied to the S-5 cohort, with patients excluded or censored upon transformation. The S-5 and Z-5 cohorts were balanced for patient characteristics through propensity scoring on prespecified prognostic factors and standardized mortality ratio weighting. Differences between treatment groups with a standardized mean difference (SMD) <0.1 were deemed balanced. Overall response rate (ORR) was compared using odds ratio (OR). Overall survival (OS), progression-free survival (PFS) and time to next treatment (TTNT) were evaluated using Kaplan-Meier analysis and hazard ratios (HR). 

Results
143 patients were identified in S-5, reducing to 85 patients after applying propensity score weights along with 86 patients in Z-5. Median follow-up time for Z-5 was 23.3 months and for S-5 was 26.2 months. Variables that were successfully matched (SMD<0.1) included POD24, number of prior LOT, relapsed vs refractory, prior stem cell transplant, size of largest node, response to prior LOT, time since last therapy and age. Despite matching, the S-5 cohort had a higher proportion of ECOG 1 vs 0 (71.0% vs 40.7%) at baseline.  

In 3L+ patients, the ORR was 42/85 (49.9%) in S-5 compared to 81/86 (94.2%) for an OR of 16.2 (95% confidence interval [CI]: 5.6-46.9). The median PFS and OS were not reached in Z-5 and in S-5 were 12.7 months and 59.8 months, respectively (Table 1). The HRs for OS and PFS were 0.42 (95%CI: 0.21-0.83) and 0.30 (95%CI: 0.18-0.49; Figure 1). In sub-group analysis of 4L+ patients, improvements in all time-to-event outcomes were more pronounced (Table 1).

Table 1. Matched time-to-event outcomes 

 

 

18 months %(95% CI)

Median month (95% CI)

Hazard ratio (95% CI)

p-value

SCHOLAR-5

   ZUMA-5       

SCHOLAR-5

   ZUMA-5        

Primary  analysis: 

3L+

OS

67.1

(54.1, 80.2)

88.3

(79.4, 93.5)

59.8

(21.9, -)

NR

(31.6, -)

0.42

(0.21, 0.83)

0.013

PFS

23.8

(11.0, 36.5)

68.8%

(57.4, 77.8)

12.7

(6.2, 14.7)

NR

(23.5, -)

0.30

(0.18, 0.49)

<0.001

TTNT

47.2

(34.2, 60.2)

69.7

(58.8, 78.3)

14.4

(6.2, 25.8)

NR

(-, -)

0.42

(0.26, 0.68)

<0.001

Sub-group  analysis: 

4L+

OS

55.0

(39.6, 70.3)

88.3

(77, 94.2)

28.4

(12.3, -)

NR

(31.6, -)

0.31

(0.15, 0.66)

0.003

PFS

12.7

(0.7, 24.6)

67.0

(52.7, 77.8)

3.5

(1.8, 12.9)

NR

(19.0, -)

0.20

(0.11 to 0.34)

<0.001

TTNT

37.7

(22.0, 53.4)

68.3

(54.9, 78.5)

6.9

(5.1, 23.5)

NR

(22.8, -)

0.38

(0.21, 0.68)

0.001

Conclusion
Compared to currently available therapies in r/r FL patients, axi-cel demonstrated a substantial and statistically significant improvement in meaningful clinical endpoints including ORR, PFS, TTNT and OS, highlighting the durable treatment effect of axi-cel. These findings suggest that axi-cel addresses an important unmet medical need for r/r FL patients.

Keyword(s): CAR-T, Clinical data, Indolent non-Hodgkin's lymphoma

Presentation during EHA2021: The Late-Breaking Oral Session will be held on Saturday, June 12, 2021 (16:00 - 17:30 CEST) and will be accessible for on-demand viewing until August 15, 2021 on the Virtual Congress platform.

Abstract: LB1904

Type: Oral Presentation

Session title: Late-Breaking Oral Session

Background
In the pivotal ZUMA-5 (Z-5) trial, axicabtagene ciloleucel (axi-cel; an autologous anti-CD19 chimeric antigen receptor T-cell therapy) demonstrated high rates of durable response in r/r FL patients, including those with high-risk disease such as patients who progressed within 24 months of initiating first-line chemoimmunotherapy (POD24).

Aims
To compare clinical outcomes from updated 18-month Z-5 to a matched sample from the international SCHOLAR-5 (S-5) external control cohort.

Methods
The international S-5 cohort source data were extracted for r/r FL patients from 7 institutions in 5 countries who initiated a third or higher (3L+) line of therapy (LOT) after July 2014. Data from the pivotal idelalisib DELTA trial was also included in the S-5 cohort. Z-5 trial eligibility criteria were applied to the S-5 cohort, with patients excluded or censored upon transformation. The S-5 and Z-5 cohorts were balanced for patient characteristics through propensity scoring on prespecified prognostic factors and standardized mortality ratio weighting. Differences between treatment groups with a standardized mean difference (SMD) <0.1 were deemed balanced. Overall response rate (ORR) was compared using odds ratio (OR). Overall survival (OS), progression-free survival (PFS) and time to next treatment (TTNT) were evaluated using Kaplan-Meier analysis and hazard ratios (HR). 

Results
143 patients were identified in S-5, reducing to 85 patients after applying propensity score weights along with 86 patients in Z-5. Median follow-up time for Z-5 was 23.3 months and for S-5 was 26.2 months. Variables that were successfully matched (SMD<0.1) included POD24, number of prior LOT, relapsed vs refractory, prior stem cell transplant, size of largest node, response to prior LOT, time since last therapy and age. Despite matching, the S-5 cohort had a higher proportion of ECOG 1 vs 0 (71.0% vs 40.7%) at baseline.  

In 3L+ patients, the ORR was 42/85 (49.9%) in S-5 compared to 81/86 (94.2%) for an OR of 16.2 (95% confidence interval [CI]: 5.6-46.9). The median PFS and OS were not reached in Z-5 and in S-5 were 12.7 months and 59.8 months, respectively (Table 1). The HRs for OS and PFS were 0.42 (95%CI: 0.21-0.83) and 0.30 (95%CI: 0.18-0.49; Figure 1). In sub-group analysis of 4L+ patients, improvements in all time-to-event outcomes were more pronounced (Table 1).

Table 1. Matched time-to-event outcomes 

 

 

18 months %(95% CI)

Median month (95% CI)

Hazard ratio (95% CI)

p-value

SCHOLAR-5

   ZUMA-5       

SCHOLAR-5

   ZUMA-5        

Primary  analysis: 

3L+

OS

67.1

(54.1, 80.2)

88.3

(79.4, 93.5)

59.8

(21.9, -)

NR

(31.6, -)

0.42

(0.21, 0.83)

0.013

PFS

23.8

(11.0, 36.5)

68.8%

(57.4, 77.8)

12.7

(6.2, 14.7)

NR

(23.5, -)

0.30

(0.18, 0.49)

<0.001

TTNT

47.2

(34.2, 60.2)

69.7

(58.8, 78.3)

14.4

(6.2, 25.8)

NR

(-, -)

0.42

(0.26, 0.68)

<0.001

Sub-group  analysis: 

4L+

OS

55.0

(39.6, 70.3)

88.3

(77, 94.2)

28.4

(12.3, -)

NR

(31.6, -)

0.31

(0.15, 0.66)

0.003

PFS

12.7

(0.7, 24.6)

67.0

(52.7, 77.8)

3.5

(1.8, 12.9)

NR

(19.0, -)

0.20

(0.11 to 0.34)

<0.001

TTNT

37.7

(22.0, 53.4)

68.3

(54.9, 78.5)

6.9

(5.1, 23.5)

NR

(22.8, -)

0.38

(0.21, 0.68)

0.001

Conclusion
Compared to currently available therapies in r/r FL patients, axi-cel demonstrated a substantial and statistically significant improvement in meaningful clinical endpoints including ORR, PFS, TTNT and OS, highlighting the durable treatment effect of axi-cel. These findings suggest that axi-cel addresses an important unmet medical need for r/r FL patients.

Keyword(s): CAR-T, Clinical data, Indolent non-Hodgkin's lymphoma

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