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Abstract

Abstract: S118

Type: Oral Presentation

Session title: Cellular, antibody and targeted therapy

Background
B2001X (NCT03123939) is a multicenter global study of tisagenlecleucel set up to provide access to pediatric and young adult patients with relapsed/refractory (r/r) acute lymphoblastic leukemia (ALL) including patients with prior anti-CD19 therapy after enrollment ended in the pivotal ELIANA (NCT02435849) study.

Aims
We report clinical outcomes and cellular kinetics of patients treated in the B2001X study, including patients with prior blinatumomab (BLINA) exposure or inotuzumab (INO) as a bridging therapy.

Methods
Eligible patients ≤21 years old at diagnosis with ≥2 relapses, refractory or post allogeneic transplant (alloSCT) relapse, were enrolled globally.

Results
As of November 4, 2019, 73 patients were enrolled; 67 patients received tisagenlecleucel. 91% received lymphodepletion chemotherapy. Among 65 patients who had ≥3 months’ follow-up or who discontinued earlier (efficacy analysis set [EAS]) median follow-up was 9.6 months (range, 0.2–16.5). Median age was 10 years (range, 2–33); 61% had prior alloSCT; 15 patients received prior BLINA and 9 patients received INO as bridging therapy. Efficacy outcomes are summarized in Table. 14 patients relapsed; 13/14 were medullary (isolated or combined with extramedullary) and 1/14 extramedullary; 9 within 6 months including 4/5 who were CD19(+). 64% had cytokine release syndrome (grade 3/4; 13%/15%; Penn scale); 24% had neurologic events (grade 3/4; 9%/2%; CTCAE v4.03). 4 deaths were reported in ≤30 days: 2 early ALL progression, 1 fatal cytokine release syndrome case associated with refractory ALL, and 1 infection with multiorgan failure. 

Transgene levels by qPCR in peripheral blood in 50 evaluable patients showed limited to no in vivo expansion in nonresponders (n = 8) vs responders (n = 42). Median duration of persistence (T last) of tisagenlecleucel was 272 days (range, 27-379) in responders. In patients with CR/CRi, Cmax (Geo-mean [CV%]) and median T last were 9,260 (124) copies/μg DNA and 154 days (range, 28-349), respectively, in patients who received INO as bridging therapy (n = 6) vs 38,500 (215) and 273 days (range, 27-379), respectively, in those who did not receive INO as bridging therapy (n = 36).

Conclusion
Efficacy and safety of tisagenlecleucel in the B2001X study remain consistent with outcomes in ELIANA. In patients with INO as bridging therapy, a trend toward suboptimal expansion was observed. In patients with prior BLINA or INO as bridging therapy, a trend toward suboptimal outcomes was observed. These observations should be interpreted with caution due to small numbers, short follow-up, and potential confounding factors.

Session topic: 02. Acute lymphoblastic leukemia - Clinical

Keyword(s): Acute lymphoblastic leukemia, CAR-T, CD19, Pediatric

Abstract: S118

Type: Oral Presentation

Session title: Cellular, antibody and targeted therapy

Background
B2001X (NCT03123939) is a multicenter global study of tisagenlecleucel set up to provide access to pediatric and young adult patients with relapsed/refractory (r/r) acute lymphoblastic leukemia (ALL) including patients with prior anti-CD19 therapy after enrollment ended in the pivotal ELIANA (NCT02435849) study.

Aims
We report clinical outcomes and cellular kinetics of patients treated in the B2001X study, including patients with prior blinatumomab (BLINA) exposure or inotuzumab (INO) as a bridging therapy.

Methods
Eligible patients ≤21 years old at diagnosis with ≥2 relapses, refractory or post allogeneic transplant (alloSCT) relapse, were enrolled globally.

Results
As of November 4, 2019, 73 patients were enrolled; 67 patients received tisagenlecleucel. 91% received lymphodepletion chemotherapy. Among 65 patients who had ≥3 months’ follow-up or who discontinued earlier (efficacy analysis set [EAS]) median follow-up was 9.6 months (range, 0.2–16.5). Median age was 10 years (range, 2–33); 61% had prior alloSCT; 15 patients received prior BLINA and 9 patients received INO as bridging therapy. Efficacy outcomes are summarized in Table. 14 patients relapsed; 13/14 were medullary (isolated or combined with extramedullary) and 1/14 extramedullary; 9 within 6 months including 4/5 who were CD19(+). 64% had cytokine release syndrome (grade 3/4; 13%/15%; Penn scale); 24% had neurologic events (grade 3/4; 9%/2%; CTCAE v4.03). 4 deaths were reported in ≤30 days: 2 early ALL progression, 1 fatal cytokine release syndrome case associated with refractory ALL, and 1 infection with multiorgan failure. 

Transgene levels by qPCR in peripheral blood in 50 evaluable patients showed limited to no in vivo expansion in nonresponders (n = 8) vs responders (n = 42). Median duration of persistence (T last) of tisagenlecleucel was 272 days (range, 27-379) in responders. In patients with CR/CRi, Cmax (Geo-mean [CV%]) and median T last were 9,260 (124) copies/μg DNA and 154 days (range, 28-349), respectively, in patients who received INO as bridging therapy (n = 6) vs 38,500 (215) and 273 days (range, 27-379), respectively, in those who did not receive INO as bridging therapy (n = 36).

Conclusion
Efficacy and safety of tisagenlecleucel in the B2001X study remain consistent with outcomes in ELIANA. In patients with INO as bridging therapy, a trend toward suboptimal expansion was observed. In patients with prior BLINA or INO as bridging therapy, a trend toward suboptimal outcomes was observed. These observations should be interpreted with caution due to small numbers, short follow-up, and potential confounding factors.

Session topic: 02. Acute lymphoblastic leukemia - Clinical

Keyword(s): Acute lymphoblastic leukemia, CAR-T, CD19, Pediatric

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