TISAGENLECLEUCEL APPEARS EFFECTIVE AND SAFE IN PEDIATRIC AND YOUNG ADULT PATIENTS WITH RELAPSED/REFRACTORY ACUTE LYMPHOBLASTIC LEUKEMIA WITH HIGH-RISK CYTOGENETIC ABNORMALITIES
Author(s): ,
Stephan Grupp
Affiliations:
Children's Hospital of Philadelphia,Philadelphia,United States
,
Shannon Maude
Affiliations:
Children's Hospital of Philadelphia,Philadelphia,United States
,
Andre Baruchel
Affiliations:
Universite Paris Diderot et Institut Universitaire d'Hematologie,Paris,France
,
Theodore W. Laetsch
Affiliations:
University of Texas Southwestern,Dallas,United States
,
Timothy Driscoll
Affiliations:
Duke University,Durham,United States
,
Muna Qayed
Affiliations:
Emory University,Atlanta,United States
,
John Levine
Affiliations:
Mount Sinai School of Medicine,New York City,United States
,
Michael Boyer
Affiliations:
University of Utah,Salt Lake City,United States
,
Joerg Krueger
Affiliations:
The Hospital for Sick Children,Toronto,Canada
,
Gary Douglas Myers
Affiliations:
Children's Mercy Hospital,Kansas City,United States
,
Christina Peters
Affiliations:
St Anna Children's Hospital,Vienna,Austria
,
Susana Rives
Affiliations:
Sant Joan de Deu Hospital,Barcelona,Spain
,
Peter Bader
Affiliations:
University Children's Hospital,Frankfurt,Germany
,
Nicolas Boissel
Affiliations:
Hopspital Saint-Louis-Univeristy,Paris,France
,
Stella Davies
Affiliations:
Cincinnati Children's Hospital,Cincinnati,United States
,
Kara Davis
Affiliations:
Stanford University,Stanford,United States
,
Eneida Nemecek
Affiliations:
Oregon Health & Science University,Portland,United States
,
Gregory Yanik
Affiliations:
University of Michigan,Ann Arbor,United States
,
Ranjan Tiwari
Affiliations:
Novartis Pharmaceuticals Corporation,East Hanover,United States
,
Srivani Konduri
Affiliations:
Novartis Pharmaceuticals Corporation,East Hanover,United States
,
Lamis Eldjerou
Affiliations:
Novartis Pharmaceuticals Corporation,East Hanover,United States
,
Andrea Chassot Agostinho
Affiliations:
Novartis Pharmaceuticals Corporation,East Hanover,United States
,
Stephen Hunger
Affiliations:
Children's Hospital of Philadelphia,Philadelphia,United States
Michael Pulsipher
Affiliations:
Children's Hospital Los Angeles,Los Angeles,United States
EHA Library. A. Grupp S. 06/16/19; 267372; S1618
Stephan A. Grupp
Stephan A. Grupp
Contributions
Abstract

Abstract: S1618

Type: Oral Presentation

Presentation during EHA24: On Sunday, June 16, 2019 from 08:15 - 08:30

Location: Elicium 1

Background
Cytogenetic and molecular genetic findings at diagnosis constitute important independent prognostic and risk stratification factors in B-cell acute lymphoblastic leukemia (ALL). Certain alterations signify high-risk (HR) cytogenetic abnormalities and are associated with poorer prognosis and inferior outcomes, particularly in patients (pts) with relapsed/refractory (r/r) disease. Tisagenlecleucel is an anti-CD19 chimeric antigen receptor (CAR)-T cell therapy approved in multiple countries/regions for the treatment of pediatric and young adult pts with r/r ALL (r/r pALL). Tisagenlecleucel has demonstrated high rates of durable responses and a manageable safety profile in the ELIANA and ENSIGN trials.

Aims
We analyzed outcomes in a subgroup of pts from the ELIANA and ENSIGN studies with reported HR cytogenetic abnormalities at enrollment, namely: hypodiploidy; t(9;22)(q34;q11.2)/BCR-ABL1; KMT2A (MLL) rearrangement; intrachromosomal amplification of chromosome 21 (iAMP21); t(17;19)(q23;p13), encoding TCF3-HLF fusion; BCR-ABL1-like; CRLF2 rearrangement; and/or TP53 mutation/deletion.

Methods
ELIANA and ENSIGN are single-arm, multicenter, phase 2 trials of tisagenlecleucel in pts with r/r pALL. The primary endpoint is overall remission rate (ORR: complete remission [CR] + CR with incomplete blood count recovery [CRi]) within 3 months per independent review committee (IRC) assessment. In this subgroup analysis, pooled efficacy and safety data from ELIANA and ENSIGN are presented for pts with HR cytogenetic abnormalities.

Results
A total of 29/137 infused pts (ELIANA 13/79, ENSIGN 16/58) were identified with HR cytogenetic abnormalities (Table). Median age was 12 years (range, 3-21 years); median previous lines of therapy was 3 (range, 1-8); and 15/29 pts received at least 1 prior hematopoietic stem cell transplant. Among all infused pts (full analysis set), 19/29 (65.5%) pts with HR cytogenetic abnormalities (vs 81/108 [75.0%] pts without the aforementioned HR cytogenetic abnormalities) from this pooled data set achieved confirmed remission per IRC assessment, and 18/19 of these responding pts were negative for minimal residual disease by flow cytometry. Of the remaining 10 pts, 4 did not reach Day 28 assessment at data cutoff, 3 died before Day 28 assessment (1 each from progressive leukemia, cerebral hemorrhage, and embolic stroke), 2 had missing assessments, and 1 did not respond to therapy. Among the 19 responding pts, 4 relapsed; the median duration of response was not reached, with estimated relapse-free probability at 12 and 24 months after remission onset of 74.6% (vs 61.7% and 58.5%, respectively, in pts without HR cytogenetic abnormalities). Median overall survival in pts with HR cytogenetic abnormalities was not reached, with estimated 12- and 24-month survival probability of 74.9% and 66.6%, respectively (vs 70.7% and 58.8%, respectively, in pts without HR cytogenetic abnormalities). Rates of select adverse events that occurred within 8 weeks after infusion in pts with HR cytogenetic abnormalities were: cytokine release syndrome (grade 3, 17.2%; grade 4, 27.6%), infections (grade 3, 13.8%; grade 4, 3.4%), cytopenias not resolved by Day 28 (grade 3, 17.2%; grade 4; 13.8%), and neurological events (grade 3, 3.4%; no grade 4 events).

Conclusion
In pts with HR cytogenetic abnormalities with historically poor prognosis, tisagenlecleucel appears effective, with high rates of durable responses, prolonged survival, and a manageable safety profile.

Clinical trial information: NCT02435849; NCT02228096.

Session topic: 2. Acute lymphoblastic leukemia - Clinical

Keyword(s): ALL, Clinical trial, Pediatric, Young adult

Abstract: S1618

Type: Oral Presentation

Presentation during EHA24: On Sunday, June 16, 2019 from 08:15 - 08:30

Location: Elicium 1

Background
Cytogenetic and molecular genetic findings at diagnosis constitute important independent prognostic and risk stratification factors in B-cell acute lymphoblastic leukemia (ALL). Certain alterations signify high-risk (HR) cytogenetic abnormalities and are associated with poorer prognosis and inferior outcomes, particularly in patients (pts) with relapsed/refractory (r/r) disease. Tisagenlecleucel is an anti-CD19 chimeric antigen receptor (CAR)-T cell therapy approved in multiple countries/regions for the treatment of pediatric and young adult pts with r/r ALL (r/r pALL). Tisagenlecleucel has demonstrated high rates of durable responses and a manageable safety profile in the ELIANA and ENSIGN trials.

Aims
We analyzed outcomes in a subgroup of pts from the ELIANA and ENSIGN studies with reported HR cytogenetic abnormalities at enrollment, namely: hypodiploidy; t(9;22)(q34;q11.2)/BCR-ABL1; KMT2A (MLL) rearrangement; intrachromosomal amplification of chromosome 21 (iAMP21); t(17;19)(q23;p13), encoding TCF3-HLF fusion; BCR-ABL1-like; CRLF2 rearrangement; and/or TP53 mutation/deletion.

Methods
ELIANA and ENSIGN are single-arm, multicenter, phase 2 trials of tisagenlecleucel in pts with r/r pALL. The primary endpoint is overall remission rate (ORR: complete remission [CR] + CR with incomplete blood count recovery [CRi]) within 3 months per independent review committee (IRC) assessment. In this subgroup analysis, pooled efficacy and safety data from ELIANA and ENSIGN are presented for pts with HR cytogenetic abnormalities.

Results
A total of 29/137 infused pts (ELIANA 13/79, ENSIGN 16/58) were identified with HR cytogenetic abnormalities (Table). Median age was 12 years (range, 3-21 years); median previous lines of therapy was 3 (range, 1-8); and 15/29 pts received at least 1 prior hematopoietic stem cell transplant. Among all infused pts (full analysis set), 19/29 (65.5%) pts with HR cytogenetic abnormalities (vs 81/108 [75.0%] pts without the aforementioned HR cytogenetic abnormalities) from this pooled data set achieved confirmed remission per IRC assessment, and 18/19 of these responding pts were negative for minimal residual disease by flow cytometry. Of the remaining 10 pts, 4 did not reach Day 28 assessment at data cutoff, 3 died before Day 28 assessment (1 each from progressive leukemia, cerebral hemorrhage, and embolic stroke), 2 had missing assessments, and 1 did not respond to therapy. Among the 19 responding pts, 4 relapsed; the median duration of response was not reached, with estimated relapse-free probability at 12 and 24 months after remission onset of 74.6% (vs 61.7% and 58.5%, respectively, in pts without HR cytogenetic abnormalities). Median overall survival in pts with HR cytogenetic abnormalities was not reached, with estimated 12- and 24-month survival probability of 74.9% and 66.6%, respectively (vs 70.7% and 58.8%, respectively, in pts without HR cytogenetic abnormalities). Rates of select adverse events that occurred within 8 weeks after infusion in pts with HR cytogenetic abnormalities were: cytokine release syndrome (grade 3, 17.2%; grade 4, 27.6%), infections (grade 3, 13.8%; grade 4, 3.4%), cytopenias not resolved by Day 28 (grade 3, 17.2%; grade 4; 13.8%), and neurological events (grade 3, 3.4%; no grade 4 events).

Conclusion
In pts with HR cytogenetic abnormalities with historically poor prognosis, tisagenlecleucel appears effective, with high rates of durable responses, prolonged survival, and a manageable safety profile.

Clinical trial information: NCT02435849; NCT02228096.

Session topic: 2. Acute lymphoblastic leukemia - Clinical

Keyword(s): ALL, Clinical trial, Pediatric, Young adult

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