KEY TAKEAWAYS
- Phase 3 B2001X trial aims to evaluate the efficacy and safety of tisagenlecleucel in pediatric and young adult patients with relapsed/refractory.
- Eligible patients ≤21 years old at diagnosis with ≥2 relapses, refractory or post alloSCT relapse, were enrolled globally.
- Efficacy outcomes showed a consistent response rate with the pivotal ELIANA study, but patients with prior BLINA or INO therapy.
- Transgene levels by qPCR in peripheral blood showed limited in vivo expansion in nonresponders and a median duration of 272 days in responders.
As enrolment in the pivotal ELIANA (NCT02435849) research closed, the B2001X (NCT03123939) project was designed to give young adults and children with relapsed/refractory (r/r) acute lymphoblastic leukemia (ALL) access to tisagenlecleucel.
Patients exposed to blinatumomab (BLINA) or who had received inotuzumab (INO) as a bridge therapy are included in this report, as are their clinical outcomes and cellular kinetics after treatment in the B2001X study. Patients with at least two relapses, refractoriness, or recurrence after allogeneic stem cell transplantation (alloSCT) were enrolled worldwide.
To date (04/11/2019), 73 patients have been enrolled, with 67 receiving tisagenlecleucel. About 91 percent were treated with lymphodepleting chemotherapy. Median follow-up was 9.6 months among the 65 patients who were followed for 3 months or who discontinued treatment early (efficacy analysis set [EAS]) (range, 0.2–16.5). 15 patients had previous BLINA, and 9 received INO as bridging therapy; the median age was 10 years old (range, 2-33); 61% had prior alloSCT. By 6 months, 9 patients relapsed, including 4/5 who were CD19(+). Thirteen of the 14 relapses were medullary (alone or in combination with extramedullary), and one was extramedullary.
Neurological problems occurred in 24% (grade 3/4; 9%/2%; CTCAE v4.03), and 64% experienced cytokine release syndrome (grade 3/4; 13%/15%; Penn scale). Within the first 30 days, there were 4 documented deaths: 2 from the early development of ALL, 1 from cytokine release syndrome associated with refractory ALL, and 1 from infection with multiorgan failure.
Fifty evaluable patients had their transgene levels measured, and the results showed that in nonresponders (n = 8), there was little to no in vivo expansion compared to responders (n = 42). Among those who responded to tisagenlecleucel, the median persistence time (T last) was 272 days (range 27-379). Patients in CR/CRi who got INO as bridging therapy (n = 6) had a Cmax (Geo-mean [CV%]) of 9,260 (124) copies/g DNA and a median T last of 154 days (range, 28-349), while patients in the control group (n = 36) had Cmax values of 38,500 (215) and median T last values of 273 days (range, 27-379). The B2001X research confirmed the safety and efficacy of tisagenlecleucel, which was previously seen in the ELIANA trial. A tendency for poor expansion was seen in patients with INO as a bridging therapy. Patients previously receiving BLINA or INO as bridging therapy tended to have inferior outcomes. Due to the low sample size, limited follow-up time, and potential confounding factors, caution is warranted when interpreting these results.
Source:https://library.ehaweb.org/eha/2020/eha25th/294938/andre.baruchel.tisagenlecleucel.for.pediatric.young.adult.patients.with.htmlf=menu%3D6%2Abrowseby%3D8%2Asortby%3D2%2Amedia%3D3%2Ace_id%3D1766%2Aot_id%3D23219%2Amarker%3D756
Clinical Trial:https://clinicaltrials.gov/ct2/show/NCT03123939
Baruchel A, Krueger J, Balduzzi A, Bittencourt H, Moerloose B, Peters C, Bader P, Boissel N, Hiramatsu H, Waldron E, Sanjeevi P, White M, Eldjerou L, & Rives S. TISAGENLECLEUCEL FOR PEDIATRIC/YOUNG ADULT PATIENTS WITH RELAPSED/REFRACTORY B-CELL ACUTE LYMPHOBLASTIC LEUKEMIA: PRELIMINARY REPORT OF B2001X FOCUSING ON PRIOR EXPOSURE TO BLINATUMOMAB AND INOTUZUMAB. (Abstract release date: 05/14/20) EHA Library. Baruchel A. 06/12/2020; 294938; S118
