The safety and efficacy of Celgene's CAR T cell therapies are under investigation and have not been established. There is no guarantee that these agents will receive health authority approval or become commercially available in any country for the uses being investigated.

Cancer Immune Response

Refresh your knowledge about the immune response to cancer, and how cancer can evade detection

CAR T Science

Learn about the science behind CAR T cell therapies

B Cell Malignancies

Learn about unmet needs in select B cell malignancies

CAR T Process

Learn what the CAR T therapy process may involve for you and your patients

CAR T Cell Therapy Is a Collaborative Process

Close collaboration between patient, healthcare team, and manufacturer is critical for CAR T cell therapies

Each CAR T cell therapy is an autologous cellular biologic that combines CAR gene constructs with an individual patient’s T cells. CAR T cell therapies require close collaboration with the entire team and ongoing engagement from the patient and their caregivers.

1 Apheresis, 2 Transport and handling, 3 Cell engineering, 4 Conditioning chemotherapy, 5 CAR T infusion, 6 Monitoring and follow-up.]
1

Apheresis

Creation of a CAR T cell therapy begins with collection of the patient’s blood and separation of the lymphocytes through apheresis (leukapheresis). Clinicians coordinate collection based on the patient’s treatment regimen to ensure the presence of sufficient numbers of T cells.1 The procedure is performed at the clinic or infusion center coordinated by the patient’s healthcare team.2

2

Transport & Handling

Once collected, the lymphocytes are immediately packaged by the clinic or infusion center for hand delivery to a centralized manufacturing facility.3 The manufacturer may require lymphocytes be shipped fresh (1°C to 10°C) or cryopreserved, depending on their shipping guidelines.4,5

3

Cell Engineering

CAR T cell engineering involves a number of steps. The apheresis product may be processed to remove any cells that inhibit T cell activation and expansion.6,7 The CAR gene construct can then be incorporated into the T cells using one of several different methods. Finally, the CAR T cells are expanded, or grown, outside the body, to an appropriate dose.8

LEARN MORE ABOUT T CELL SUBTYPES

4

Conditioning Chemotherapy

The patient's healthcare team administers conditioning chemotherapy to deplete lymphocytes before CAR T cell therapy, which may improve expansion and persistence.2

LEARN MORE ABOUT CAR T CELL EXPANSION AND PERSISTENCE

5

CAR T Cell Infusion

The patient’s healthcare team administers the prepared CAR T cell therapy. Administration directions vary depending on the CAR T cell therapy.

6

Monitoring & Follow-up

As part of a manufacturer's certification of a CAR T cell treatment center, clinics may be required to implement a program to train healthcare staff who prescribe, dispense, or administer CAR T cell therapy about how to monitor, manage, and educate patients on adverse events.

Serious toxicities are known to occur with CAR T cell therapies. These toxicities may require immediate medical attention and may sometimes result in death. They occur in the first few days to weeks after CAR T cell treatment.2,9

Two of the most serious adverse events are Cytokine-release syndrome (CRS) and Neurological toxicity (NT)9:

  •  CRS symptoms can be progressive, must include fever at the onset and may include hypotension, capillary leak (hypoxia), and end organ dysfunction9
  •  NT symptoms or signs can be progressive and may include aphasia, altered level of consciousness, impairment of cognitive skills, motor weakness, seizures, and cerebral edema9

Other adverse events include5:

  •  Serious Infections
  •  Prolonged Cytopenias
  •  Hypogammaglobulinemia

Rare cases of fulminant hemophagocytic lymphohistiocytosis (HLH), characterized by severe immune activation, lymphohistiocytic tissue infiltration, and immune-mediated multiorgan failure, have also been reported.10

These are not all of the side effects associated with CAR T cell therapies, and the side effects are different from product to product.

Further information on adverse event monitoring and management can be obtained from CAR T cell therapy manufacturers or study investigators.

How CAR T cell therapy is used

Two CAR T cell therapies have been approved in third or later line for adult patients with relapsed or refractory large B cell lymphoma, and one has been approved for pediatric and young adult patients with B cell precursor acute lymphoblastic leukemia (ALL) that is refractory or in second or later relapse. CAR T cell therapies are being investigated in relapsed or refractory B cell malignancies, including DLBCL, multiple myeloma, CLL, and follicular lymphoma.11,12

As CAR T cell therapies continue to be investigated for B cell malignancies, they may become available for appropriate patients who need them.13,14

References:

  1. Wang X, Rivière I. Mol Ther–Oncolytics. 2016;3:16015. doi:10.1038/mto.2016.15.
  2. Batlevi CL, Matsuki E, Brentjens RJ, Younes A. Nat Rev Clin Oncol. 2016;13:25-40.
  3. Dai H, Wang Y, Lu X, Han W. J Natl Cancer Inst. 2016;108:1-14.
  4. Roberts ZJ, Better M, Bot A, Roberts MR, Ribas A. Leuk Lymphoma. 2018;59:1785-1796. doi:10.1080/10428194.2017.1387905.
  5. Novartis. Accessed October 18, 2018.
  6. Fesnak A, Lin C, Siegel DL, Maus MV. Transfus Med Rev. 2016;30:139-145.
  7. Bryn T, Yaqub S, Mahic M, Henjum K, Aandahl EM, Tasken K. Int Immunol. 2008;20:235-245.
  8. Lee DW, Barrett DM, Mackall C, Orentas R, Grupp SA. Clin Cancer Res. 2012;18:2780-2791.
  9. Lee DW, Santomasso BD, Locke FL, et al. Biol Blood Marrow Transplant. 2019;25:625-638. doi:10.1016/j.bbmt.2018.12.758.
  10. Neelapu SS, Tummala S, Kebriaei P, et al. Nat Rev Clin Oncol. 2018;15:47-62.
  11. ClinicalTrials.gov. Accessed September 29, 2018.
  12. Stenner F, Renner C. Front Oncol. 2018;8:219.
  13. Maus MV, Levine BL. Oncologist. 2016;21:608-617.
  14. Khalil DN, Smith EL, Brentjens RJ, Wolchok JD. Nat Rev Clin Oncol. 2016;13:273-290.

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