Three-Year Update of Tisagenlecleucel in Pediatric and Young Adult Patients With Relapsed/Refractory Acute Lymphoblastic Leukemia in the ELIANA Trial

Abstract

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.In the primary analysis of the global phase II ELIANA trial (ClinicalTrials.gov identifier: NCT02435849), tisagenlecleucel provided an overall remission rate of 81% in pediatric and young adult patients with relapsed or refractory B-cell acute lymphoblastic leukemia (R/R B-ALL), with 59% of responders remaining relapse-free at 12 months. Here, we report an update on efficacy, safety, and patient-reported quality of life in 79 pediatric and young adult patients with R/R B-ALL following a median follow-up of 38.8 months. The overall remission rate was 82%. The median event-free survival was 24 months, and the median overall survival was not reached. Event-free survival was 44% (95% CI, 31 to 57) and overall survival was 63% (95% CI, 51 to 73) at 3 years overall (most events occur within the first 2 years). The estimated 3-year relapse-free survival with and without censoring for subsequent therapy was 52% (95% CI, 37 to 66) and 48% (95% CI, 34 to 60), respectively. No new or unexpected long-term adverse events were reported. Grade 3/4 adverse events were reported in 29% of patients > 1 year after infusion; grade 3/4 infection rate did not increase > 1 year after infusion. Patients reported improvements in quality of life up to 36 months after infusion. These findings demonstrate favorable long-term safety and suggest tisagenlecleucel as a curative treatment option for heavily pretreated pediatric and young adult patients with R/R B-ALL.

Conflict of interest statement

Theodore W. LaetschStock and Other Ownership Interests: Advanced MicrobubblesConsulting or Advisory Role: Novartis, Bayer, Cellectis, Aptitude Health, Clinical Education Alliance, Deciphera, Jumo Health, Massive Bio, Med Learning Group, Medscape, Physicans' Education Resource, Y-mAbs Therapeutics, AI Therapeutics, Jazz Pharmaceuticals, GentiBio, Menarini, Pyramid BiosciencesResearch Funding: Pfizer (Inst), Novartis (Inst), Bayer (Inst), AbbVie (Inst), Amgen (Inst), Atara Biotherapeutics (Inst), Bristol Myers Squibb (Inst), Lilly (Inst), Epizyme (Inst), GlaxoSmithKline (Inst), Janssen (Inst), Jubilant Pharmaceuticals (Inst), Novella Clinical (Inst), Servier (Inst), Foundation Medicine (Inst), Merck Sharp & Dohme (Inst), Turning Point Therapeutics (Inst) Shannon L. MaudeConsulting or Advisory Role: Novartis, KiteResearch Funding: Novartis (Inst), Wugen, Inc (Inst)Patents, Royalties, Other Intellectual Property: PCT/US2017/044425: Combination Therapies of Car and PD-1 InhibitorsTravel, Accommodations, Expenses: Novartis Susana RivesHonoraria: Novartis, Kite/Gilead, Celgene/Bristol Myers Squibb, Shire/ServierConsulting or Advisory Role: Servier, Amgen, Novartis, Kite/Gilead, Shire/Servier, Celgene/Bristol Myers Squibb, Cellectis, Jazz PharmaceuticalsSpeakers' Bureau: NovartisResearch Funding: Novartis (Inst)Travel, Accommodations, Expenses: Novartis, Shire/Servier, Cellectis, Jazz Pharmaceuticals Hidefumi HiramatsuHonoraria: Novar PharmaConsulting or Advisory Role: Novartis Henrique BittencourtConsulting or Advisory Role: Novartis Canada Pharmaceuticals Inc, Jazz PharmaceuticalsSpeakers' Bureau: Novartis Oncology Canada Peter BaderHonoraria: Medac (Inst), Riemser (Inst), Neovii (Inst)Consulting or Advisory Role: Novartis (Inst), Amgen (Inst), Miltenyi (Inst), Servier (Inst)Speakers' Bureau: Novartis (Inst), Amgen (Inst), Riemser (Inst), Medac (Inst), Miltenyi (Inst), Servier (Inst)Research Funding: Medac (Inst), Neovii (Inst), Riemser (Inst)Patents, Royalties, Other Intellectual Property: Patent on MSC licensend to Medac André BaruchelLeadership: DBV Technologies, lysogen, Medday Pharmaceuticals, Ascendis PharmaStock and Other Ownership Interests: DBV Technologies, Ascendis PharmaHonoraria: Novartis, Kite, a Gilead company, AstraZenecaConsulting or Advisory Role: Jazz Pharmaceuticals, Novartis, Servier, CelgeneResearch Funding: Jazz Pharmaceuticals (Inst), Servier (Inst)Travel, Accommodations, Expenses: Jazz Pharmaceuticals, Sanofi, Servier Michael BoyerHonoraria: NovartisEmployment: Thunder BiotechLeadership: Thunder Biotech Barbara De MoerlooseConsulting or Advisory Role: NovartisUncompensated Relationships: Novartis (Inst), Gilead Sciences (Inst), Articulate Science, Jazz Pharmaceuticals Muna QayedHonoraria: Novartis, Vertex, Medexus, Jazz Pharmaceuticals, MesoblastConsulting or Advisory Role: NovartisTravel, Accommodations, Expenses: Novartis Jochen BuechnerHonoraria: Novartis, Pfizer, KiteConsulting or Advisory Role: Novartis, Janssen (Inst), Amgen (Inst)Speakers' Bureau: Novartis Michael A. PulsipherThis author is a member of the Journal of Clinical Oncology Editorial Board. Journal policy recused the author from having any role in the peer review of this manuscript.Honoraria: Novartis, MesoblastConsulting or Advisory Role: Novartis, Medexus Pharmaceuticals, Equillium, Gentibio, Vertex, Bluebird BioResearch Funding: Adaptive Biotechnologies, Miltenyi Biotec Gary Douglas MyersHonoraria: NovartisConsulting or Advisory Role: NovartisSpeakers' Bureau: NovartisResearch Funding: Novartis (Inst) Heather E. StefanskiConsulting or Advisory Role: NovartisSpeakers' Bureau: Novartis Paul L. MartinConsulting or Advisory Role: Neovii Biotech GmbH, Genentech, Enlivex Therapeutics, and PharmacyclicsResearch Funding: Novartis (Inst), Bluebird Bio (Inst), AbGenomics (Inst) Eneida NemecekConsulting or Advisory Role: Novartis, Medexus, Atara Bio Christina PetersHonoraria: Neovii, Jazz Pharmaceuticals, NovartisConsulting or Advisory Role: Amgen, Neovii, NovartisSpeakers' Bureau: Medac, Riemser, AmgenResearch Funding: Medac (Inst), Neovii (Inst), Riemser (Inst), Jazz Pharmaceuticals (Inst), Amgen (Inst)Travel, Accommodations, Expenses: Neovii, Jazz Pharmaceuticals, Novartis Seong Lin KhawHonoraria: Novartis Kara L. DavisHonoraria: NovartisResearch Funding: Jazz Pharmaceuticals Joerg KruegerEmployment: JanssenConsulting or Advisory Role: Novartis, Kite/Gilead, SOBIOther Relationship: Canadian Agency for Drugs and Technologies in Health (CADTH) Adriana BalduzziSpeakers' Bureau: Novartis, Amgen, MedacTravel, Accommodations, Expenses: Novartis, Medac, Neovii Nicolas BoisselHonoraria: Amgen, ARIAD/Incyte, Novartis, Servier, Astellas Pharma, Bristol Myers Squibb, Jazz Pharmaceuticals, Celgene, Sanofi, PfizerConsulting or Advisory Role: Amgen, Novartis, Servier, PfizerResearch Funding: Amgen, Novartis, Bristol Myers Squibb, Jazz PharmaceuticalsExpert Testimony: Amgen Ranjan TiwariEmployment: Novartis Darragh O’DonovanEmployment: Novartis Ireland LtdStock and Other Ownership Interests: Novartis Stephan A. GruppHonoraria: TCR2 Therapeutics, Eureka Therapeutics, CellectisConsulting or Advisory Role: Novartis, Jazz Pharmaceuticals, Janssen, Cellular Biomedicine Group, Roche, Adaptimmune, Alimera Sciences, Cabaletta Bio, CRISPR Therapeutics/VertexResearch Funding: Novartis (Inst), Kite/Gilead (Inst), Servier (Inst), Jazz Pharmaceuticals (Inst), Vertex (Inst)Patents, Royalties, Other Intellectual Property: UPenn Toxicity management patent (Inst)Expert Testimony: Juno TherapeuticsNo other potential conflicts of interest were reported.

Figures

FIG 1.

(A) DOR, (B) EFS, and (C) OS. (A) DOR—patients who achieved a BOR of CR/CRi are included. One patient who achieved a BOR of CRi within 6 months (day 173) is included. Time is relative to detection of remission. (B) EFS—time is relative to first tisagenlecleucel infusion date. (C) OS—time is relative to first tisagenlecleucel infusion date. BOR, best overall response; CR, complete remission; CRi, complete remission with incomplete hematologic recovery; DOR, duration of remission; EFS, event-free survival; NE, not estimable; OS, overall survival.

FIG 2.

Duration of remission by B-cell recovery time point. Time is relative to first tisagenlecleucel infusion date. EFS, event-free survival; NE, not estimable.