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Lisocabtagene maraleucel as second-line therapy in adults with relapsed or refractory large B-cell lymphoma who were not intended for haematopoietic stem cell transplantation (PILOT): an open-label, phase 2 study.
Sehgal, Alison; Hoda, Daanish; Riedell, Peter A; Ghosh, Nilanjan; Hamadani, Mehdi; Hildebrandt, Gerhard C; Godwin, John E; Reagan, Patrick M; Wagner-Johnston, Nina; Essell, James; Nath, Rajneesh; Solomon, Scott R; Champion, Rebecca; Licitra, Edward; Fanning, Suzanne; Gupta, Neel; Dubowy, Ronald; D'Andrea, Aleco; Wang, Lei; Ogasawara, Ken; Thorpe, Jerill; Gordon, Leo I.
Afiliación
  • Sehgal A; University of Pittsburgh Medical Center, Hillman Cancer Center, Pittsburgh, PA, USA. Electronic address: sehgalar@upmc.edu.
  • Hoda D; Intermountain Healthcare, LDS Hospital, Salt Lake City, UT, USA.
  • Riedell PA; Department of Medicine, Section of Hematology/Oncology, University of Chicago Medical Center, Chicago, IL, USA.
  • Ghosh N; Levine Cancer Institute, Atrium Health, Charlotte, NC, USA.
  • Hamadani M; BMT and Cellular Therapy Program, Medical College of Wisconsin, Milwaukee, WI, USA.
  • Hildebrandt GC; Markey Cancer Center, University of Kentucky, Lexington, KY, USA.
  • Godwin JE; Providence Cancer Center, Earle A Chiles Research Institute, Portland, OR, USA.
  • Reagan PM; University of Rochester Medical Center, Rochester, NY, USA.
  • Wagner-Johnston N; Department of Oncology, Johns Hopkins Hospital, Baltimore, MD, USA.
  • Essell J; Oncology Hematology Care, Cincinnati, OH, USA.
  • Nath R; Department of Stem Cell Transplant and Cellular Therapy, Banner MD Anderson Cancer Center, Gilbert, AZ, USA.
  • Solomon SR; Transplant and Cellular Immunotherapy Program, Northside Hospital Cancer Institute, Atlanta, GA, USA.
  • Champion R; Hematologic Malignancies Program, Norton Cancer Institute, Louisville, KY, USA.
  • Licitra E; Astera Cancer Care, East Brunswick, NJ, USA.
  • Fanning S; Prisma Health, Greenville, SC, USA.
  • Gupta N; Stanford Cancer Genetics Clinic, Palo Alto, CA, USA.
  • Dubowy R; Bristol Myers Squibb, Seattle, WA, USA.
  • D'Andrea A; Celgene, a Bristol-Myers Squibb company, Boudry, Switzerland.
  • Wang L; Bristol Myers Squibb, Seattle, WA, USA.
  • Ogasawara K; Bristol Myers Squibb, Lawrence Township, NJ, USA.
  • Thorpe J; Bristol Myers Squibb, Seattle, WA, USA.
  • Gordon LI; Northwestern University, Feinberg School of Medicine, Robert H Lurie Comprehensive Cancer Center, Chicago, IL, USA.
Lancet Oncol ; 23(8): 1066-1077, 2022 08.
Article en En | MEDLINE | ID: mdl-35839786
ABSTRACT

BACKGROUND:

Patients with relapsed or refractory large B-cell lymphoma after first-line treatment who are not intended for haematopoietic stem-cell transplantation (HSCT) have poor outcomes and limited treatment options. We assessed the antitumour activity and safety of lisocabtagene maraleucel, an autologous, CD19-directed chimeric antigen receptor (CAR) T-cell product, as second-line treatment in adults with relapsed or refractory large B-cell lymphoma not intended for HSCT.

METHODS:

PILOT, an open-label, phase 2 trial done at 18 clinical sites in the USA, included adults aged 18 years or older who had relapsed or refractory large B-cell lymphoma and PET-positive disease, had received first-line therapy containing an anthracycline and a CD20-targeted agent, were not intended for HSCT by their physician, and met at least one prespecified transplantation not intended criterion. Patients received lymphodepleting chemotherapy (intravenous fludarabine 30 mg/m2 and intravenous cyclophosphamide 300 mg/m2 daily for 3 days) followed 2-7 days later by two sequential lisocabtagene maraleucel infusions (equal target doses of CD8+ and CD4+ CAR+ T cells for a total target dose of 100 × 106 CAR+ T cells). The primary endpoint was the overall response rate and was assessed in all patients who received lisocabtagene maraleucel and had confirmed PET-positive disease before lisocabtagene maraleucel administration based on an independent review committee according to the Lugano 2014 criteria. Safety was assessed in all patients who received lisocabtagene maraleucel. Patient follow-up is ongoing. This study is registered with ClinicalTrials.gov, NCT03483103.

FINDINGS:

Between July 26, 2018, and Sept 24, 2021 (data cutoff for the primary analysis), 74 patients underwent leukapheresis and 61 received lisocabtagene maraleucel (efficacy and safety sets); median age was 74 years (IQR 70-78), 24 (39%) patients were women versus 37 (61%) men, and 54 (89%) patients were White. 16 (26%) of 61 patients had an Eastern Cooperative Oncology Group performance status of 2, 33 (54%) had refractory disease, 13 (21%) relapsed within 1 year of first-line therapy, and 15 (25%) relapsed after 12 months of first-line therapy. Median on-study follow-up was 12·3 months (IQR 6·1-18·0). 49 (80% [95% CI 68-89]; p<0·0001) patients had an overall response. The most common grade 3 or worse treatment-emergent adverse events were neutropenia (29 [48%] patients), leukopenia (13 [21%]), and thrombocytopenia (12 [20%]). Lisocabtagene maraleucel-related serious treatment-emergent adverse events were reported in 13 (21%) patients. There were no treatment-related deaths. Cytokine release syndrome occurred in 23 (38%; grade 3 in one) patients and neurological events in 19 (31%; grade 3 in three) patients, with no grade 4 events or deaths.

INTERPRETATION:

These results support lisocabtagene maraleucel as a potential second-line treatment in patients with large B-cell lymphoma for whom HSCT is not intended.

FUNDING:

Juno Therapeutics, a Bristol-Myers Squibb company.
Asunto(s)

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Trombocitopenia / Linfoma Folicular / Linfoma de Células B Grandes Difuso / Trasplante de Células Madre Hematopoyéticas Límite: Adult / Aged / Female / Humans / Male Idioma: En Año: 2022 Tipo del documento: Article

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Trombocitopenia / Linfoma Folicular / Linfoma de Células B Grandes Difuso / Trasplante de Células Madre Hematopoyéticas Límite: Adult / Aged / Female / Humans / Male Idioma: En Año: 2022 Tipo del documento: Article