Kymriah vs. Yescarta [UPDATED]

August 20, 2019 Guides, Scientific Blog Tags: 7 Comments

Kymriah® and Yescarta® are currently the only two FDA-approved CAR-T cell therapy products available on the market in the United States. Do you have trouble distinguishing between them? We created a simple chart to showcase some of the similarities and differences between the two therapies:

Company Novartis Kite/Gilead
Generic Name CTL019
Tisagenlecleucel
KTE-C19
Axicabtagen ciloleucel
FDA Breakthrough Therapy Designation Yes Yes
Date of Initial FDA Approval August 2017 October 2017
FDA Approved Indications Acute lymphoblastic leukemia (ALL)
Diffuse large B-cell lymphoma (DLBCL)
DLBCL
Non-Hodgkins lymphoma
Approx. Cost Per Treatment $475,000 USD for ALL
$373,000 USD for DLBCL
$373,000 USD
Approx. Response Time 1 month 1 month
Side Effects Cytokine release syndrome
Neurotoxicity
Cytokine release syndrome
Neurotoxicity
Disease Free Survival/Remission Rate 62% for ALL
64% for DLBCL
51%
Manufacturing Time 22 days 17 days
Gene Editing Vector Lentivirus Retrovirus
Promoter EF1a MSCV
ScFv (CD19) FMC63 FMC63
Signaling Domain 4-1BB zeta CD28 zeta
Hinge and TM CD8 alpha CD28
Cell Culture Frozen
CD3/28 beads
Fresh
PBMC/CD3
CAR-T Persistence At least 1-7 years < 6 weeks
Treatment Type Autologous Autologous
Kymriah vs. Yescarta Infographic Guide

Comparison Guide

Download our one page comparison guide for free:


Glossary:

Types of Cancer

  • Acute lymphoblastic leukemia (ALL): also known as acute lymphocytic leukemia, quickly progressing cancer of the blood and bone marrow that leads to creation of immature white blood cells, most common type of cancer in children
  • Diffuse large B-cell lymphoma (DLBCL): most common type of non-Hodgkin lymphoma in adults, affects B cells, usually occurs with age
  • Non-Hodgkin’s lymphoma: usually develops in the lymph nodes and lymphatic tissue though in some cases, can affect bone marrow and blood, can begin in C or T cells but ~90% of cases start in B cells
  • Leukemia vs. Lymphoma: both are blood cell cancers but leukemias begin in the bone marrow while lymphomas tend to affect lymph nodes

Cell Therapy Treatment Basics

  • PBMC: peripheral blood mononuclear cell; any peripheral blood cell having a round nucleus – these consist of lymphocytes (T cells, B cells, NK cells) and monocytes.
  • CAR-T Persistence: promotion of long-term anti-tumor effects, T cells persist in vivo to ensure long-term therapeutic effects of treatment and prevent tumor relapse
  • Autologous vs. Allogeneic: autologous treatments use a person’s own cells, while allogeneic treatments use cells from a donor whose human leukocyte antigens (HLA) are acceptable matches to the patient’s

Side Effects of CAR-T Therapy

  • Cytokine release syndrome (CRS): condition that occurs post CAR-T cell treatment due to the rapid release cytokines from affected immune cells, manifests as flu-like symptoms but can be potentially life-threatening, can be treated symptomatically but may require corticosteroids, tocilizumab or siltuximab
  • Tocilizumab: also known as Actemra, immunosuppressive drug, made by Genentech/Roche, humanized monoclonal antibody against the IL-6 receptor, FDA approved in August 2017 for treatment of CRS after CAR-T cell therapy
  • Siltuximab: anti-IL-6 chimeric monoclonal antibody, direct IL-6 blocker (as opposed to indirect mechanism of tocilizumab)
  • Neurotoxicity: damage to the nervous system, associated with CRS, symptoms may include confusion; delirium; aphasia; seizure; limb weakness or numbness; loss of memory, vision or intellect; headache; cognitive and behavioral problems
  • B-cell aplasia: result of “on-target, off-tumor” toxicity; depletion of all B cells including healthy cells, requires chronic treatment with gamma globulin replacement; occurs when anti-CD19 CAR-T cells kill normal lymphocytes that express CD19, putting the patient at high risk of developing infections

Viral Vectors

  • Retrovirus: retroviruses are a family of RNA viruses that produce reverse transcriptase, which copies the viral RNA into DNA to insert into the host cell’s genome.
  • Lentiviruses: subtype of retroviruses that can infect both quiescent and mitotically active cell types, while other retroviruses are only capable of infecting actively dividing cell types.

Promoters

  • Promoters: DNA sequences located upstream of a gene that define where transcription by RNA polymerase begins
    • EF1alpha: human elongation factor-1 alpha; a promoter of human origin, drives robust, constitutive, long-term gene expression in cell types where other promoters have diminished activity or have been silenced (e.g. stem cells)
    • MSCV: murine stem cell virus; a retroviral expression system that contains vectors that are optimized for introducing and expressing target genes in pluripotent cell lines.

Components of Chimeric Antigen Receptors

  • ScFv (CD19): Single-chain variable fragment; the extracellular antigen recognition domain, a fusion protein of the variable regions of the heavy and light chains of immunoglobulins, connected by a short linker peptide; CD19 is expressed at normal to high levels in B cell malignancies.
  • FMC63: This antibody specifically binds to human CD19, which is a B-lymphocyte antigen used as a biomarker in CAR-T cell therapy
  • Signaling Domain: function is to transduce extracellular binding signal into CAR T cells and to initiate the activation of downstream signaling cascades
  • 4-1BB zeta: an activation-induced costimulatory molecule, an important regulator of immune response; induced when T cells receive antigen-specific signals and subsequently triggers cytokine release
  • CD28 zeta: T-cell co-stimulatory receptor that enhances activation and signaling after recognition of CD19; inclusion of CD28 may increase proliferation of T cells and antitumor activity compared to inclusion of the CD3-zeta chain alone
  • Hinge and TM: hinge domain and transmembrane spacer; hinge domain is a structure between the targeting moiety and the T cell plasma membrane, enhances CAR T cells migratory capacity, contributes to CAR T cell expansion, and can increase antitumor efficacy; the length and the composition of the extracellular spacer domain is crucial in optimizing the design for CAR-T.
  • CD3/28: cluster of differentiation 3; cell co-receptor helps to activate both the cytotoxic T cell and T helper cells. CD28 signaling domain may increase proliferation of T cells and antitumor activity compared to the inclusion of CD3 zeta chain alone

References:

Get exclusive updates direct to your inbox.

7 Comments

    • Dr. Alyssa Master 4 months Reply

      Thank you! We will make the change.

  1. Avery 4 months Reply

    Update should also be made on the cost of Kymriah since it is different for ALL and DLBCL.

    • Dr. Alyssa Master 4 months Reply

      The update has been added. Thank you!

  2. chris heath 4 months Reply

    sorry, but those remission rates are not correct.

    • Dr. Alyssa Master 4 months Reply

      Hi! We are always looking to improve our content. If you could share with us sources for the correct statistics, we would be happy to update.

    • Marion 2 months Reply

      what are the correct remission rates?

Leave a reply

Your email address will not be published. Required fields are marked *