News & Perspective

First CAR T cell therapy approved for lymphoma patients

Hematology
10 months ago, OP Editor

Axicabtagene ciloleucel is the second chimeric antigen receptor (CAR) T cell therapy approved by the FDA and the first for adults with certain types of large B-cell lymphoma.1 The strong patient responses to CAR T cell therapies, which now include tisagenlecleucel and axicabtagene, have led to the accelerated approval of this innovative class of treatment.1,2

CAR T cell therapy, unlike other approved cancer therapies, consists of autologous T cells that are genetically modified to produce a CAR protein, allowing the T cells to identify and eliminate CD19-expressing normal and malignant cells.2 As suggested by Dr. James Kochenderfer, a lead investigator on the early National Cancer Institute (NCI) trials, the rapid translation from the therapy’s initial development to an FDA approval “is an important accomplishment.”2

“Today marks another milestone in the development of a whole new scientific paradigm for the treatment of serious diseases. In just several decades, gene therapy has gone from being a promising concept to a practical solution to deadly and largely untreatable forms of cancer,” said Dr. Scott Gottlieb, FDA Commissioner.1

Axicabtagene is approved for the treatment of adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, primary mediastinal large B-cell lymphoma, high-grade B-cell lymphoma, and DLBCL arising from follicular lymphoma.3 The approval of axicabtagene may offer hope to patients who relapsed after multiple rounds of chemotherapy or a stem-cell transplant, since “their chance of complete remission from salvage therapy is only 7%.” said Dr. David Chang, Kite Pharma’s chief medical officer (now a part of Gilead Sciences).4

With axicabtagene, the objective response rate (ORR) was 72%, with a complete remission (CR) rate of 51%.3,5 The estimated median duration of response (DOR) among patients achieving CR was not reached (95% CI: 8.1 months to not estimable [NE]).3,5 Among patients achieving partial remission (PR), the estimated median DOR was 2.1 months (95% CI: 1.3 to 5.3).3,5

“Many of the patients that received CAR T cell therapy had already relapsed several times with traditional treatments such as chemotherapy or hematopoietic stem cell transplant. Now, thanks to this new therapy, many patients are in remission for months.” said Dr. Frederick L. Locke, ZUMA-1 Co-Lead Investigator and Vice Chair of the Department of Blood and Marrow Transplant and Cellular Immunotherapy at Moffitt Cancer Center in Tampa, Florida.6

Of note, the key concerns with CAR T cell therapies are the risks of cytokine release syndrome (CRS) and neurological effects.2,7 Nearly 30% of patients experienced a serious neurological event and 13% had a potentially dangerous CRS.2,3 To address these concerns, FDA is requiring staff at hospitals that want to be able to offer axicabtagene to undergo special training and certification.2

Nonetheless, CAR T cell therapies “will be a critical part of lymphoma therapy for a long time”, as there is a strong rationale to test them earlier in the disease course of patients with lymphoma, said Dr. Kochenderfer.2 Moreover, Dr. Julia Vose, chief of Hematology/Oncology at Nebraska Medicine, also commented, “there will soon be additional clinical trials that will likely expand the number of patients who are eligible for this therapy.”2

 

 

  1. FDA approves CAR-T cell therapy to treat adults with certain types of large B-cell lymphoma. FDA News Release. 2017 (Accessed November 2, 2017, at https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm581216.htm).
  2. With FDA Approval for Advanced Lymphoma, Second CAR T-Cell Therapy Moves to the Clinic. National Cancer Institute. 2017 (Accessed November 2, 2017, at https://www.cancer.gov/news-events/cancer-currents-blog/2017/yescarta-fda-lymphoma).
  3. FDA approves axicabtagene ciloleucel for large B-cell lymphoma. FDA News Release. 2017 (Accessed November 2, 2017, at https://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm581296.htm).
  4. Move over, Novartis: Kite and Gilead break into CAR-T market with early axi-cel nod. FiercePharma. 2017 (Accessed November 2, 2017, at http://www.fiercepharma.com/regulatory/kite-and-gilead-join-novartis-red-hot-car-t-market-early-axi-cel-approval).
  5. Kite’s Yescarta™ (Axicabtagene Ciloleucel) Becomes First CAR T Therapy Approved by the FDA for the Treatment of Adult Patients With Relapsed or Refractory Large B-Cell Lymphoma After Two or More Lines of Systemic Therapy. BusinessWire. 2017 (Accessed November 1, 2017, at http://www.businesswire.com/news/home/20171018006639/en/Kite%E2%80%99s-Yescarta%E2%84%A2-Axicabtagene-Ciloleucel-CAR-Therapy-Approved).
  6. Kite’s Yescarta™ (Axicabtagene Ciloleucel) Becomes First CAR T Therapy Approved by the FDA for the Treatment of Adult Patients With Relapsed or Refractory Large B-Cell Lymphoma After Two or More Lines of Systemic Therapy. Gilead Press Releases. 2017 (Accessed November 6, 2017, at http://www.gilead.com/news/press-releases/2017/10/kites-yescarta-axicabtagene-ciloleucel-becomes-first-car-t-therapy-approved-by-the-fda-for-the-treatment-of-adult-patients-with-relapsed-or-refractory-large-bcell-lymphoma-after-two-or-more-lines-of-systemic-therapy).
  7. CAR T Cell Immunotherapy Approved for Adult Non-Hodgkin Lymphoma Patients. Cancer Research Institute. 2017 (Accessed November 6, 2017, at https://www.cancerresearch.org/blog/october-2017/car-t-cell-yescarta-approved-lymphoma).

Tags

Menu Section