June 2023 Clinical Case of the Month
Title: CAR T-cell therapy for the treatment of relapsed/refractory DLBCL
Submitted by: Real case treated at Mayo Clinic in Jacksonville, FL, USA
Physicians expert perspective: Firas Baidoun and Mohamed A. Kharfan-Dabaja
A 45-year-old woman was referred to our center for treatment of refractory diffuse large B-cell lymphoma (DLBCL). Her past medical history consisted of hormone receptor negative/HER-2 positive breast cancer in her 30s treated with neoadjuvant chemotherapy, surgical resection, radiation therapy and trastuzumab maintenance for 1 year. Her DLBCL presented as an ileum mass and mesenteric lymph nodes. Front-line therapy consisted of chemoimmunotherapy with cyclophosphamide, doxorubicin, vincristine and prednisolone plus rituximab (R-CHOP). Response assessment after 3 cycles of R-CHOP documented evidence of disease progression. Her second line therapy consisted of a chemoimmunotherapy combination of ifosfamide, carboplatinum and etoposide plus rituximab (R-ICE). After 3 cycles of R-ICE, response assessment showed evidence of persistent disease. The patient was evaluated for treatment with chimeric antigen receptor T-cell therapy (CAR T-cell). Vital organ work up demonstrated adequate cardiac, hepatic, pulmonary and renal function. Also, infectious disease work up did not show evidence of active infections; and work up for HIV, hepatitis B and hepatitis C were all negative. She received lymphodepleting chemotherapy consisting of fludarabine plus cyclophosphamide (days -5, -4, and -3) followed by infusion of axicabtagene ciloleucel (axi-cel) on day 0. Post CAR T-cell response assessment confirmed complete metabolic response (CR) on day +30 after the procedure. Subsequent radiologic evaluation at 3 months confirmed continuous CR. Her most recent evaluation at 3 years post CAR T-cell infusion continues to demonstrate CR.
The patient would like to know for what her expected 5-year overall survival.
CAR T-cell therapy has revolutionized the treatment of relapsed/refractory (R/R) DLBCL, particularly in patients who had failed 2 or more prior lines of systemic chemoimmunotherapy. Prior to CAR T-cell, the probability of attaining a CR to third-line conventional chemoimmunotherapy was estimated to range between 2% to 15% based on the SCHOLAR-1 study1. The ZUMA 1 study which evaluated the efficacy of axicabtagene ciloleucel in 101 patients with R/R large B cell lymphoma (69% had received 3 or more prior lines of therapy)2. This study showed that a CR was attained in 55% of cases. Moreover, a recently published 5-year follow up of ZUMA 1 showed that 5-year overall survival rate was 42.6% (all patients) and 64.4% in those patients who achieved a CR to axi-cel3.
Correct Answer – C
- Crump M, Neelapu SS, Farooq U, et al. Outcomes in refractory diffuse large B-cell lymphoma: results from the international SCHOLAR-1 study [published correction appears in Blood. 2018 Feb 1;131(5):587-588]. Blood. 2017;130(16):1800-1808. doi:10.1182/blood-2017-03-769620
- Neelapu SS, Locke FL, Bartlett NL, et al. Axicabtagene Ciloleucel CAR T-Cell Therapy in Refractory Large B-Cell Lymphoma. N Engl J Med. 2017;377(26):2531-2544. doi:10.1056/NEJMoa1707447
- Neelapu SS, Jacobson CA, Ghobadi A, et al. Five-year follow-up of ZUMA-1 supports the curative potential of axicabtagene ciloleucel in refractory large B-cell lymphoma. Blood. 2023;141(19):2307-2315. doi:10.1182/blood.2022018893
Mohamed A. Kharfan-Dabaja, MD, MBA, FACP
Professor of Medicine
Director, Blood and Marrow Transplantation and Cellular Therapies
Director, Inpatient Hematology Unit
Medical Director, Cancer Research Office (Mayo Clinic Florida Campus)
Firas Baidoun, MD, FACP
Mayo Clinic Florida
Future Clinical Case of the Month
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