LISOCABTAGENE MARALEUCEL FOR TREATMENT OF SECOND-LINE TRANSPLANT NONELIGIBLE RELAPSED/REFRACTORY AGGRESSIVE LARGE B-CELL NON-HODGKIN LYMPHOMA: UPDATED RESULTS FROM THE PILOT STUDY
Author(s): ,
Nilanjan Ghosh
Affiliations:
Levine Cancer Institute/Atrium Health,Charlotte,United States
,
Alison Sehgal
Affiliations:
University of Pittsburgh Medical Center, Hillman Cancer Center,Pittsburgh,United States
,
Gerhard Hildebrandt
Affiliations:
University of Kentucky Markey Cancer Center,Lexington,United States
,
John Godwin
Affiliations:
Providence Cancer Center, Earle A Chiles Research Institute,Portland,United States
,
Nina Wagner-Johnston
Affiliations:
The Johns Hopkins Hospital,Baltimore,United States
,
Daanish Hoda
Affiliations:
Intermountain Healthcare, Loveland Clinic for Blood Cancer Therapy,Salt Lake City,United States
,
Edward Licitra
Affiliations:
Regional Cancer Care Associates,East Brunswick,United States
,
Javier Munoz
Affiliations:
Banner MD Anderson Cancer Center,Gilbert,United States
,
Nikolaus Trede
Affiliations:
Juno Therapeutics, a Bristol-Myers Squibb company,Seattle,United States
,
Lei Wang
Affiliations:
Juno Therapeutics, a Bristol-Myers Squibb company,Seattle,United States
,
Jerill Thorpe
Affiliations:
Juno Therapeutics, a Bristol-Myers Squibb company,Seattle,United States
Leo Gordon
Affiliations:
Northwestern University Feinberg School of Medicine, Robert H. Lurie Comprehensive Cancer Center,Chicago,United States
EHA Library. Ghosh N. 06/12/20; 295064; S244
Nilanjan Ghosh
Nilanjan Ghosh
Contributions
Abstract

Abstract: S244

Type: Oral Presentation

Presentation during EHA25: All oral abstract presentations will be made available on the on-demand Virtual Congress platform as of Friday, June 12 at 08:30 CEST and will be accessible until October 15, 2020.

Session title: Aggressive Lymphomas: Cellular and bispecific antibody therapies

Background
Patients with aggressive large B-cell non-Hodgkin lymphoma (NHL) who are relapsed/refractory (R/R) after first-line immunochemotherapy and not eligible for high-dose chemotherapy and hematopoietic stem cell transplantation (HSCT) have a poor prognosis and no established standard of care. Lisocabtagene maraleucel (liso-cel) is an investigational, CD19-directed, defined composition, 4-1BB chimeric antigen receptor (CAR) T cell product infused at equal target doses of CD8+ and CD4+ CAR+ T cells.

Aims
The ongoing, open-label, phase 2 PILOT study is the first to assess the safety and efficacy of liso-cel as second-line (2L) therapy in transplant noneligible (TNE) patients (NCT03483103).

Methods
Eligible patients had aggressive R/R diffuse large B-cell lymphoma not otherwise specified (de novo or transformed follicular lymphoma [FL]), high-grade B-cell lymphoma, or FL grade 3B and received 1 line of prior therapy containing an anthracycline and anti-CD20 agent. Patients were deemed TNE by the treating center/physician and meeting ≥1 objective criteria: age ≥70 years, Eastern Cooperative Oncology Group performance status (ECOG PS) 2, or impaired organ function (diffusing capacity of the lung for carbon monoxide ≤60% [but saturated oxygen ≥92% and Common Terminology Criteria for Adverse Events ≤1 dyspnea], left ventricular ejection fraction ≥40% to <50%, creatinine clearance >30 to <60 mL/min, or aspartate aminotransferase/alanine aminotransferase >2 to ≤5 × upper limit of normal). Liso-cel (100 × 106 CAR+ T cells) was administered 2–7 days after lymphodepletion (LD) with fludarabine/cyclophosphamide. The primary endpoint is objective response rate (ORR); key secondary endpoints are adverse events (AEs) and complete response (CR) rate.

Results
At data cutoff, 25 patients had received LD followed by liso-cel infusion. Patient characteristics are summarized in the Table. Overall, 48% (n=12) had high tumor burden and 48% were primary refractory. Of 25 patients, 18 (72%) had grade ≥3 treatment-emergent AEs, 40% of which were cytopenias. No grade 5 AEs occurred within the first 30 days after liso-cel. Five patients (20%) had cytokine release syndrome (CRS) and 3 (12%) had neurological events (NEs). No grade 3/4 CRS was observed; 2 patients (8%) had grade 3/4 NEs. Five patients (20%) received tocilizumab and/or dexamethasone for CRS/NEs. At a median follow-up of 3.5 months, the ORR was 80% (95% confidence interval, 59–93; n=20); 48% of patients (n=12) achieved CR. 

Patient characteristics

Liso-cel–treated patients (n=25)

Age, years (range)

72 (53–85)

Male, n (%)

16 (64)

TNE screening criteria, n (%)

Age ≥70 years

ECOG PS 2

Organ function

≥2 TNE criteria

 

17 (68)

7 (28)

6 (24)

6 (24)

R/R to last therapy, n (%)

13 (52)/12 (48)

SPD ≥50 cm2/LDH ≥500 U/L, n (%)

10 (43.5)/5 (20)

HCT-CI score

Median (range) (n=24)

≥3, n (%)

 

2.5 (0–9)

12 (50)

HCT-CI, HSCT comorbidity index; LDH, lactate dehydrogenase; SPD, sum of the product of perpendicular diameters.

Conclusion
These interim data suggest that elderly and/or comorbid patients with R/R aggressive large B-cell NHL, who are not eligible for high-dose chemotherapy and HSCT, can receive 2L liso-cel with similar safety and efficacy to that previously reported in third-line patients (Abramson, ASH 2019 #241). Updated data with longer follow-up will be presented.

Session topic: 19. Aggressive Non-Hodgkin lymphoma - Clinical

Keyword(s): B cell lymphoma, Cellular therapy, Refractory, Relapsed lymphoma

Abstract: S244

Type: Oral Presentation

Presentation during EHA25: All oral abstract presentations will be made available on the on-demand Virtual Congress platform as of Friday, June 12 at 08:30 CEST and will be accessible until October 15, 2020.

Session title: Aggressive Lymphomas: Cellular and bispecific antibody therapies

Background
Patients with aggressive large B-cell non-Hodgkin lymphoma (NHL) who are relapsed/refractory (R/R) after first-line immunochemotherapy and not eligible for high-dose chemotherapy and hematopoietic stem cell transplantation (HSCT) have a poor prognosis and no established standard of care. Lisocabtagene maraleucel (liso-cel) is an investigational, CD19-directed, defined composition, 4-1BB chimeric antigen receptor (CAR) T cell product infused at equal target doses of CD8+ and CD4+ CAR+ T cells.

Aims
The ongoing, open-label, phase 2 PILOT study is the first to assess the safety and efficacy of liso-cel as second-line (2L) therapy in transplant noneligible (TNE) patients (NCT03483103).

Methods
Eligible patients had aggressive R/R diffuse large B-cell lymphoma not otherwise specified (de novo or transformed follicular lymphoma [FL]), high-grade B-cell lymphoma, or FL grade 3B and received 1 line of prior therapy containing an anthracycline and anti-CD20 agent. Patients were deemed TNE by the treating center/physician and meeting ≥1 objective criteria: age ≥70 years, Eastern Cooperative Oncology Group performance status (ECOG PS) 2, or impaired organ function (diffusing capacity of the lung for carbon monoxide ≤60% [but saturated oxygen ≥92% and Common Terminology Criteria for Adverse Events ≤1 dyspnea], left ventricular ejection fraction ≥40% to <50%, creatinine clearance >30 to <60 mL/min, or aspartate aminotransferase/alanine aminotransferase >2 to ≤5 × upper limit of normal). Liso-cel (100 × 106 CAR+ T cells) was administered 2–7 days after lymphodepletion (LD) with fludarabine/cyclophosphamide. The primary endpoint is objective response rate (ORR); key secondary endpoints are adverse events (AEs) and complete response (CR) rate.

Results
At data cutoff, 25 patients had received LD followed by liso-cel infusion. Patient characteristics are summarized in the Table. Overall, 48% (n=12) had high tumor burden and 48% were primary refractory. Of 25 patients, 18 (72%) had grade ≥3 treatment-emergent AEs, 40% of which were cytopenias. No grade 5 AEs occurred within the first 30 days after liso-cel. Five patients (20%) had cytokine release syndrome (CRS) and 3 (12%) had neurological events (NEs). No grade 3/4 CRS was observed; 2 patients (8%) had grade 3/4 NEs. Five patients (20%) received tocilizumab and/or dexamethasone for CRS/NEs. At a median follow-up of 3.5 months, the ORR was 80% (95% confidence interval, 59–93; n=20); 48% of patients (n=12) achieved CR. 

Patient characteristics

Liso-cel–treated patients (n=25)

Age, years (range)

72 (53–85)

Male, n (%)

16 (64)

TNE screening criteria, n (%)

Age ≥70 years

ECOG PS 2

Organ function

≥2 TNE criteria

 

17 (68)

7 (28)

6 (24)

6 (24)

R/R to last therapy, n (%)

13 (52)/12 (48)

SPD ≥50 cm2/LDH ≥500 U/L, n (%)

10 (43.5)/5 (20)

HCT-CI score

Median (range) (n=24)

≥3, n (%)

 

2.5 (0–9)

12 (50)

HCT-CI, HSCT comorbidity index; LDH, lactate dehydrogenase; SPD, sum of the product of perpendicular diameters.

Conclusion
These interim data suggest that elderly and/or comorbid patients with R/R aggressive large B-cell NHL, who are not eligible for high-dose chemotherapy and HSCT, can receive 2L liso-cel with similar safety and efficacy to that previously reported in third-line patients (Abramson, ASH 2019 #241). Updated data with longer follow-up will be presented.

Session topic: 19. Aggressive Non-Hodgkin lymphoma - Clinical

Keyword(s): B cell lymphoma, Cellular therapy, Refractory, Relapsed lymphoma

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