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LISOCABTAGENE MARALEUCEL (LISO-CEL) AS SECOND-LINE THERAPY FOR R/R LARGE B-CELL LYMPHOMA (LBCL) IN PATIENTS NOT INTENDED FOR HSCT: PRIMARY ANALYSIS FROM THE PHASE 2 PILOT STUDY
Author(s): ,
Alison Sehgal
Affiliations:
University of Pittsburgh Medical Center, Hillman Cancer Center,Pittsburgh,États-unis;University of Pittsburgh Medical Center, Hillman Cancer Center,Pittsburgh,Vereinigte Staaten;University of Pittsburgh Medical Center, Hillman Cancer Center,Pittsburgh,Stati Uniti;University of Pittsburgh Medical Center, Hillman Cancer Center,Pittsburgh,United States;University of Pittsburgh Medical Center, Hillman
,
Daanish Hoda
Affiliations:
Intermountain Healthcare, Loveland Clinic for Blood Cancer Therapy,Salt Lake City,États-unis;Intermountain Healthcare, Loveland Clinic for Blood Cancer Therapy,Salt Lake City,Vereinigte Staaten;Intermountain Healthcare, Loveland Clinic for Blood Cancer Therapy,Salt Lake City,Stati Uniti;Intermountain Healthcare, Loveland Clinic for Blood Cancer Therapy,Salt Lake City,United States;Intermountain He
,
Peter A. Riedell
Affiliations:
University of Chicago Comprehensive Cancer Center,Chicago,États-unis;University of Chicago Comprehensive Cancer Center,Chicago,Vereinigte Staaten;University of Chicago Comprehensive Cancer Center,Chicago,Stati Uniti;University of Chicago Comprehensive Cancer Center,Chicago,United States;University of Chicago Comprehensive Cancer Center,Chicago,Estados Unidos;University of Chicago Comprehensive Can
,
Nilanjan Ghosh
Affiliations:
Levine Cancer Institute, Atrium Health,Charlotte,États-unis;Levine Cancer Institute, Atrium Health,Charlotte,Vereinigte Staaten;Levine Cancer Institute, Atrium Health,Charlotte,Stati Uniti;Levine Cancer Institute, Atrium Health,Charlotte,United States;Levine Cancer Institute, Atrium Health,Charlotte,Estados Unidos;Levine Cancer Institute, Atrium Health,Charlotte,Verenigde Staten;Levine Cancer Inst
,
Mehdi Hamadani
Affiliations:
BMT & Cellular Therapy Program, Medical College of Wisconsin,Milwaukee,États-unis;BMT & Cellular Therapy Program, Medical College of Wisconsin,Milwaukee,Vereinigte Staaten;BMT & Cellular Therapy Program, Medical College of Wisconsin,Milwaukee,Stati Uniti;BMT & Cellular Therapy Program, Medical College of Wisconsin,Milwaukee,United States;BMT & Cellular Thera
,
Gerhard C. Hildebrandt
Affiliations:
Markey Cancer Center, University of Kentucky,Lexington,États-unis;Markey Cancer Center, University of Kentucky,Lexington,Vereinigte Staaten;Markey Cancer Center, University of Kentucky,Lexington,Stati Uniti;Markey Cancer Center, University of Kentucky,Lexington,United States;Markey Cancer Center, University of Kentucky,Lexington,Estados Unidos;Markey Cancer Center, University of Kentucky,Lexington
,
John E. Godwin
Affiliations:
Providence Cancer Center, Earle A. Chiles Research Institute,Portland,États-unis;Providence Cancer Center, Earle A. Chiles Research Institute,Portland,Vereinigte Staaten;Providence Cancer Center, Earle A. Chiles Research Institute,Portland,Stati Uniti;Providence Cancer Center, Earle A. Chiles Research Institute,Portland,United States;Providence Cancer Center, Earle A. Chiles Research Institute,Por
,
Patrick Reagan
Affiliations:
University of Rochester Medical Center,Rochester,États-unis;University of Rochester Medical Center,Rochester,Vereinigte Staaten;University of Rochester Medical Center,Rochester,Stati Uniti;University of Rochester Medical Center,Rochester,United States;University of Rochester Medical Center,Rochester,Estados Unidos;University of Rochester Medical Center,Rochester,Verenigde Staten;University of Roch
,
Nina Wagner-Johnston
Affiliations:
Johns Hopkins Hospital,Baltimore,États-unis;Johns Hopkins Hospital,Baltimore,Vereinigte Staaten;Johns Hopkins Hospital,Baltimore,Stati Uniti;Johns Hopkins Hospital,Baltimore,United States;Johns Hopkins Hospital,Baltimore,Estados Unidos;Johns Hopkins Hospital,Baltimore,Verenigde Staten;Johns Hopkins Hospital,Baltimore,Estados Unidos;Johns Hopkins Hospital,Baltimore,United States;Johns Hopkins Hospi
,
James Essell
Affiliations:
Oncology Hematology Care,Cincinnati,États-unis;Oncology Hematology Care,Cincinnati,Vereinigte Staaten;Oncology Hematology Care,Cincinnati,Stati Uniti;Oncology Hematology Care,Cincinnati,United States;Oncology Hematology Care,Cincinnati,Estados Unidos;Oncology Hematology Care,Cincinnati,Verenigde Staten;Oncology Hematology Care,Cincinnati,Estados Unidos;Oncology Hematology Care,Cincinnati,United St
,
Rajneesh Nath
Affiliations:
Banner MD Anderson Cancer Center,Gilbert,États-unis;Banner MD Anderson Cancer Center,Gilbert,Vereinigte Staaten;Banner MD Anderson Cancer Center,Gilbert,Stati Uniti;Banner MD Anderson Cancer Center,Gilbert,United States;Banner MD Anderson Cancer Center,Gilbert,Estados Unidos;Banner MD Anderson Cancer Center,Gilbert,Verenigde Staten;Banner MD Anderson Cancer Center,Gilbert,Estados Unidos;Banner MD
,
Scott R. Solomon
Affiliations:
Northside Hospital Cancer Institute,Atlanta,États-unis;Northside Hospital Cancer Institute,Atlanta,Vereinigte Staaten;Northside Hospital Cancer Institute,Atlanta,Stati Uniti;Northside Hospital Cancer Institute,Atlanta,United States;Northside Hospital Cancer Institute,Atlanta,Estados Unidos;Northside Hospital Cancer Institute,Atlanta,Verenigde Staten;Northside Hospital Cancer Institute,Atlanta,Esta
,
Rebecca Champion
Affiliations:
Norton Cancer Institute,Louisville,États-unis;Norton Cancer Institute,Louisville,Vereinigte Staaten;Norton Cancer Institute,Louisville,Stati Uniti;Norton Cancer Institute,Louisville,United States;Norton Cancer Institute,Louisville,Estados Unidos;Norton Cancer Institute,Louisville,Verenigde Staten;Norton Cancer Institute,Louisville,Estados Unidos;Norton Cancer Institute,Louisville,United States;Nor
,
Edward Licitra
Affiliations:
Astera Cancer Care,East Brunswick,États-unis;Astera Cancer Care,East Brunswick,Vereinigte Staaten;Astera Cancer Care,East Brunswick,Stati Uniti;Astera Cancer Care,East Brunswick,United States;Astera Cancer Care,East Brunswick,Estados Unidos;Astera Cancer Care,East Brunswick,Verenigde Staten;Astera Cancer Care,East Brunswick,Estados Unidos;Astera Cancer Care,East Brunswick,United States;Astera Canc
,
Suzanne Fanning
Affiliations:
Prisma Health,Greenville,États-unis;Prisma Health,Greenville,Vereinigte Staaten;Prisma Health,Greenville,Stati Uniti;Prisma Health,Greenville,United States;Prisma Health,Greenville,Estados Unidos;Prisma Health,Greenville,Verenigde Staten;Prisma Health,Greenville,Estados Unidos;Prisma Health,Greenville,United States;Prisma Health,Greenville,USA
,
Neel Gupta
Affiliations:
Stanford Cancer Genetics Clinic,Palo Alto,États-unis;Stanford Cancer Genetics Clinic,Palo Alto,Vereinigte Staaten;Stanford Cancer Genetics Clinic,Palo Alto,Stati Uniti;Stanford Cancer Genetics Clinic,Palo Alto,United States;Stanford Cancer Genetics Clinic,Palo Alto,Estados Unidos;Stanford Cancer Genetics Clinic,Palo Alto,Verenigde Staten;Stanford Cancer Genetics Clinic,Palo Alto,Estados Unidos;Sta
,
Ronald Dubowy
Affiliations:
Bristol Myers Squibb,Seattle,États-unis;Bristol Myers Squibb,Seattle,Vereinigte Staaten;Bristol Myers Squibb,Seattle,Stati Uniti;Bristol Myers Squibb,Seattle,United States;Bristol Myers Squibb,Seattle,Estados Unidos;Bristol Myers Squibb,Seattle,Verenigde Staten;Bristol Myers Squibb,Seattle,Estados Unidos;Bristol Myers Squibb,Seattle,United States;Bristol Myers Squibb,Seattle,USA
,
Aleco D'Andrea
Affiliations:
Celgene, a Bristol-Myers Squibb Company,Boudry,Suisse;Celgene, a Bristol-Myers Squibb Company,Boudry,Schweiz;Celgene, a Bristol-Myers Squibb Company,Boudry,Svizzera;Celgene, a Bristol-Myers Squibb Company,Boudry,Switzerland;Celgene, a Bristol-Myers Squibb Company,Boudry,Suiza;Celgene, a Bristol-Myers Squibb Company,Boudry,Zwitserland;Celgene, a Bristol-Myers Squibb Company,Boudry,Suíça;Celgene, a
,
Lei Wang
Affiliations:
Bristol Myers Squibb,Seattle,États-unis;Bristol Myers Squibb,Seattle,Vereinigte Staaten;Bristol Myers Squibb,Seattle,Stati Uniti;Bristol Myers Squibb,Seattle,United States;Bristol Myers Squibb,Seattle,Estados Unidos;Bristol Myers Squibb,Seattle,Verenigde Staten;Bristol Myers Squibb,Seattle,Estados Unidos;Bristol Myers Squibb,Seattle,United States;Bristol Myers Squibb,Seattle,USA
Leo I. Gordon
Affiliations:
Northwestern University, Feinberg School of Medicine, Robert H. Lurie Comprehensive Cancer Center,Chicago,États-unis;Northwestern University, Feinberg School of Medicine, Robert H. Lurie Comprehensive Cancer Center,Chicago,Vereinigte Staaten;Northwestern University, Feinberg School of Medicine, Robert H. Lurie Comprehensive Cancer Center,Chicago,Stati Uniti;Northwestern University, Feinberg School
(Abstract release date: 05/26/22) EHA Library. Sehgal A. 06/11/22; 357122; S258
Alison Sehgal
Alison Sehgal
Contributions
Abstract
Presentation during EHA2022: All Oral presentations will be presented between Friday, June 10 and Sunday, June 12 and will be accessible for on-demand viewing from Monday, June 20 until Monday, August 15, 2022 on the Congress platform.

Abstract: S258

Type: Oral Presentation

Session title: Gene therapy and cellular immunotherapy - Clinical 1

Background
Patients with relapsed or refractory (R/R) LBCL after first-line treatment who are unable to undergo high-dose chemotherapy (HDCT) and hematopoietic stem cell transplantation (HSCT) have poor outcomes and limited treatment options.

Aims
PILOT (NCT03483103) evaluated liso-cel, an autologous, CD19-directed chimeric antigen receptor (CAR) T cell product, as second-line treatment in patients with R/R LBCL not intended for HSCT.

Methods
Eligible patients were adults with R/R LBCL after first-line treatment who were not deemed candidates for HDCT and HSCT by their physician and met ≥ 1 frailty criteria as follows: age ≥ 70 years, Eastern Cooperative Oncology Group performance status (ECOG PS) of 2, diffusing capacity for carbon monoxide ≤ 60%, left ventricular ejection fraction < 50%, creatinine clearance < 60 mL/min, or alanine aminotransferase/aspartate aminotransferase > 2 × the upper limit of normal. Bridging therapy was allowed. Patients received lymphodepletion with cyclophosphamide and fludarabine, followed 2–7 days later by liso-cel infusion at a target dose of 100 × 106 CAR+ T cells. Cytokine release syndrome (CRS) was graded per Lee 2014 criteria. Neurological events (NE) were defined as investigator-identified neurological adverse events related to liso-cel and graded using the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.03. The primary endpoint was objective response rate (ORR) per independent review committee; all patients had ≥ 6 months of follow-up from first response.

Results
Of 74 patients who underwent leukapheresis, 61 received liso-cel and 1 received nonconforming product (ie, product wherein one of the CD8 or CD4 cell components did not meet one of the requirements to be considered liso-cel). Common reasons for preinfusion dropout included death and loss of eligibility (5 each). For liso-cel–treated patients, median age was 74 years (range, 53–84; 79% ≥ 70 years) and 69%, 26%, and 5% met 1, 2, and 3 frailty criteria, respectively; 26% had ECOG PS of 2 and 44% had Hematopoietic Cell Transplantation-specific Comorbidity Index score ≥ 3. After first-line treatment, 54% were chemotherapy refractory, 21% relapsed within 12 months, and 25% relapsed after 12 months; 51% of patients received bridging chemotherapy. Median (range) on-study follow-up was 12.3 months (1.2–26.5). ORR and complete response rate were 80% and 54%, respectively (Table). Median duration of response and progression-free survival were 12.1 months and 9.0 months, respectively. Median overall survival has not been reached. The most frequent treatment-emergent adverse events (TEAE) were neutropenia (51%), fatigue (39%), and CRS (38%), with grade 3 CRS in 1 patient (2%) and no grade 4/5 CRS events. Any-grade NEs were seen in 31% (n = 19) of patients; grade 3 NEs occurred in 5% (n = 3) of patients and no grade 4/5 NEs were reported. Seven percent (n = 4) received tocilizumab only, 3% (n = 2) received corticosteroids only, and 20% (n = 12) received both tocilizumab and corticosteroids for treatment of CRS and/or NEs. Overall, grade ≥ 3 TEAEs occurred in 79% (n = 48) of patients, with grade 5 TEAEs in 2 patients (both due to COVID-19). Two patients (3%) had grade 3/4 infections and 15 (25%) had grade ≥3 neutropenia at Day 29.

Conclusion
In the PILOT study, liso-cel as second-line treatment in patients with LBCL who met ≥ 1 frailty criteria and for whom HSCT was not intended demonstrated substantial and durable overall and complete responses, with no new safety concerns.

Keyword(s): B cell lymphoma, CAR-T, Clinical trial



© 2022 American Society of Clinical Oncology, Inc. Reused with permission. This abstract was accepted and previously presented at the 2022 ASCO Annual Meeting. All rights reserved.
Presentation during EHA2022: All Oral presentations will be presented between Friday, June 10 and Sunday, June 12 and will be accessible for on-demand viewing from Monday, June 20 until Monday, August 15, 2022 on the Congress platform.

Abstract: S258

Type: Oral Presentation

Session title: Gene therapy and cellular immunotherapy - Clinical 1

Background
Patients with relapsed or refractory (R/R) LBCL after first-line treatment who are unable to undergo high-dose chemotherapy (HDCT) and hematopoietic stem cell transplantation (HSCT) have poor outcomes and limited treatment options.

Aims
PILOT (NCT03483103) evaluated liso-cel, an autologous, CD19-directed chimeric antigen receptor (CAR) T cell product, as second-line treatment in patients with R/R LBCL not intended for HSCT.

Methods
Eligible patients were adults with R/R LBCL after first-line treatment who were not deemed candidates for HDCT and HSCT by their physician and met ≥ 1 frailty criteria as follows: age ≥ 70 years, Eastern Cooperative Oncology Group performance status (ECOG PS) of 2, diffusing capacity for carbon monoxide ≤ 60%, left ventricular ejection fraction < 50%, creatinine clearance < 60 mL/min, or alanine aminotransferase/aspartate aminotransferase > 2 × the upper limit of normal. Bridging therapy was allowed. Patients received lymphodepletion with cyclophosphamide and fludarabine, followed 2–7 days later by liso-cel infusion at a target dose of 100 × 106 CAR+ T cells. Cytokine release syndrome (CRS) was graded per Lee 2014 criteria. Neurological events (NE) were defined as investigator-identified neurological adverse events related to liso-cel and graded using the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.03. The primary endpoint was objective response rate (ORR) per independent review committee; all patients had ≥ 6 months of follow-up from first response.

Results
Of 74 patients who underwent leukapheresis, 61 received liso-cel and 1 received nonconforming product (ie, product wherein one of the CD8 or CD4 cell components did not meet one of the requirements to be considered liso-cel). Common reasons for preinfusion dropout included death and loss of eligibility (5 each). For liso-cel–treated patients, median age was 74 years (range, 53–84; 79% ≥ 70 years) and 69%, 26%, and 5% met 1, 2, and 3 frailty criteria, respectively; 26% had ECOG PS of 2 and 44% had Hematopoietic Cell Transplantation-specific Comorbidity Index score ≥ 3. After first-line treatment, 54% were chemotherapy refractory, 21% relapsed within 12 months, and 25% relapsed after 12 months; 51% of patients received bridging chemotherapy. Median (range) on-study follow-up was 12.3 months (1.2–26.5). ORR and complete response rate were 80% and 54%, respectively (Table). Median duration of response and progression-free survival were 12.1 months and 9.0 months, respectively. Median overall survival has not been reached. The most frequent treatment-emergent adverse events (TEAE) were neutropenia (51%), fatigue (39%), and CRS (38%), with grade 3 CRS in 1 patient (2%) and no grade 4/5 CRS events. Any-grade NEs were seen in 31% (n = 19) of patients; grade 3 NEs occurred in 5% (n = 3) of patients and no grade 4/5 NEs were reported. Seven percent (n = 4) received tocilizumab only, 3% (n = 2) received corticosteroids only, and 20% (n = 12) received both tocilizumab and corticosteroids for treatment of CRS and/or NEs. Overall, grade ≥ 3 TEAEs occurred in 79% (n = 48) of patients, with grade 5 TEAEs in 2 patients (both due to COVID-19). Two patients (3%) had grade 3/4 infections and 15 (25%) had grade ≥3 neutropenia at Day 29.

Conclusion
In the PILOT study, liso-cel as second-line treatment in patients with LBCL who met ≥ 1 frailty criteria and for whom HSCT was not intended demonstrated substantial and durable overall and complete responses, with no new safety concerns.

Keyword(s): B cell lymphoma, CAR-T, Clinical trial



© 2022 American Society of Clinical Oncology, Inc. Reused with permission. This abstract was accepted and previously presented at the 2022 ASCO Annual Meeting. All rights reserved.

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