TWO-YEAR SURVIVAL WITH AXICABTAGENE CILOLEUCEL IN RELAPSED OR REFRACTORY LARGE B-CELL LYMPHOMA: AN UPDATED ANALYSIS
Author(s): ,
Ibrahim Diakite
Affiliations:
Pharmerit International,Bethesda,United States
,
Vincent W. Lin
Affiliations:
Kite, a Gilead Company,Santa Monica,United States
,
Sven Klijn
Affiliations:
Pharmerit International,Rotterdam,Netherlands
,
Lynn Navale
Affiliations:
Kite, a Gilead Company,Santa Monica,United States
,
Anna G. Purdum
Affiliations:
Kite, a Gilead Company,Santa Monica,United States
,
Elisabeth Fenwick
Affiliations:
Pharmerit International,Oxford,United Kingdom
,
Marc Botteman
Affiliations:
Pharmerit International,Bethesda,United States
Ben van Hout
Affiliations:
University of Sheffield,Sheffield,United Kingdom
EHA Library. Adolf T. 05/16/19; 267536; PB1782
Tiffany Adolf
Tiffany Adolf
Contributions
Abstract

Abstract: PB1782

Type: Publication Only

Background
Relapsed/refractory large B cell lymphoma is historically associated with a poor prognosis, with a median overall survival (OS) of 6.3 months. In the 2-year update of the ZUMA-1 trial of axicabtagene ciloleucel (axi-cel), median OS was not reached after a median follow-up of 27.1 months. Prior analysis at 1-year suggests that traditional parametric survival models cannot accurately estimate long-term OS with axi-cel when a large proportion of patients achieve durable remissions, thereby supporting the use of a mixture cure model (MCM) for survival extrapolations (Bansal, et al. Biol Blood Marrow Transplant. 2018).

Aims
We analyzed the updated 2-year ZUMA-1 data to further explore the robustness of MCM.

Methods
The ZUMA-1 data were analyzed using a traditional parametric model, MCM, a general mixture model (GMM), and an integrated Markov cure model (IMCM). The MCM assumed patients with long-term OS would have similar mortality as the age-adjusted general population. The GMM relaxed this assumption by separately fitting and then combining parametric survival functions for poor- and good-prognosis patients in a single survival function. The IMCM simultaneously accounted for OS and disease progression in a single framework. All parameters were estimated via maximum likelihood estimations, and model fit was assessed via Akaike information criterion (AIC).

Results
The best-fitting traditional model estimated a mean OS of 10.6 years (AIC = 444.3). The best-fitting MCM estimated a mean OS of 13.5 years, with a 51.0% long-term OS fraction (AIC = 439.3). The best-fitting GMM produced a mean OS of 13.5 years, with a 52.7% long-term OS fraction (AIC = 442.1). The best-fitting IMCM estimated a mean OS of 13.4 years, with a 50.5% long-term OS fraction (AIC = 916.6). The higher AIC for GMM and IMCM is partly because of specifying more parameters than MCM.

Conclusion
Analyzing the updated ZUMA-1 2-year data, both the GMM and IMCM showed good model fit and results consistent with those of the MCM. These results support the long-term survival associated with axi-cel in relapsed/refractory large B cell lymphoma driven by the ≥ 50% long-term OS rates.

Session topic: 19. Aggressive Non-Hodgkin lymphoma - Clinical

Keyword(s): Antigen-specific T cells, Large granular lymphocytic leukaemia, Targeted therapy

Abstract: PB1782

Type: Publication Only

Background
Relapsed/refractory large B cell lymphoma is historically associated with a poor prognosis, with a median overall survival (OS) of 6.3 months. In the 2-year update of the ZUMA-1 trial of axicabtagene ciloleucel (axi-cel), median OS was not reached after a median follow-up of 27.1 months. Prior analysis at 1-year suggests that traditional parametric survival models cannot accurately estimate long-term OS with axi-cel when a large proportion of patients achieve durable remissions, thereby supporting the use of a mixture cure model (MCM) for survival extrapolations (Bansal, et al. Biol Blood Marrow Transplant. 2018).

Aims
We analyzed the updated 2-year ZUMA-1 data to further explore the robustness of MCM.

Methods
The ZUMA-1 data were analyzed using a traditional parametric model, MCM, a general mixture model (GMM), and an integrated Markov cure model (IMCM). The MCM assumed patients with long-term OS would have similar mortality as the age-adjusted general population. The GMM relaxed this assumption by separately fitting and then combining parametric survival functions for poor- and good-prognosis patients in a single survival function. The IMCM simultaneously accounted for OS and disease progression in a single framework. All parameters were estimated via maximum likelihood estimations, and model fit was assessed via Akaike information criterion (AIC).

Results
The best-fitting traditional model estimated a mean OS of 10.6 years (AIC = 444.3). The best-fitting MCM estimated a mean OS of 13.5 years, with a 51.0% long-term OS fraction (AIC = 439.3). The best-fitting GMM produced a mean OS of 13.5 years, with a 52.7% long-term OS fraction (AIC = 442.1). The best-fitting IMCM estimated a mean OS of 13.4 years, with a 50.5% long-term OS fraction (AIC = 916.6). The higher AIC for GMM and IMCM is partly because of specifying more parameters than MCM.

Conclusion
Analyzing the updated ZUMA-1 2-year data, both the GMM and IMCM showed good model fit and results consistent with those of the MCM. These results support the long-term survival associated with axi-cel in relapsed/refractory large B cell lymphoma driven by the ≥ 50% long-term OS rates.

Session topic: 19. Aggressive Non-Hodgkin lymphoma - Clinical

Keyword(s): Antigen-specific T cells, Large granular lymphocytic leukaemia, Targeted therapy

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