CAR-T therapy process

CAR-T cell therapy is a targeted, personalized therapy that involves the infusion of patients’ autologous T cells genetically reengineered to fight cancer.1

The T cells are altered to express a CAR, which combines the specificity of a monoclonal antibody with the cytotoxic and memory functions of T cells.2 CAR-T cells may multiply and differentiate into central or effector memory cells, which may promote the survival of CAR-T cells.3,4

After cell collection and cryopreservation, cell manufacturing, and infusion, these altered T cells can now fight and destroy the cancerous cells they could not find before.

Watch this video below to understand the mechanism of action for CAR-T cell therapy.
CAR-T cell therapy is a targeted, personalized therapy that involves the infusion of patients’ autologous T cells genetically reengineered to fight cancer.1

The T cells are altered to express a CAR, which combines the specificity of a monoclonal antibody with the cytotoxic and memory functions of T cells.2 CAR-T cells may multiply and differentiate into central or effector memory cells, which may promote the survival of CAR-T cells.3,4

After cell collection and cryopreservation, cell manufacturing, and infusion, these altered T cells can now fight and destroy the cancerous cells they could not find before.

Watch this video below to understand the mechanism of action for CAR-T cell therapy.

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HOW CAR-T WORKS

1 CELL COLLECTION

1 CELL COLLECTION

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1

Blood from the patient is drawn and separated to collect their T cells through apheresis (leukapheresis). This process occurs over 3 to 6 hours. Within 24 hours, the leukapheresis material is cryopreserved and sent to a manufacturing facility for reprogramming.1

CELL COLLECTION

2 CELL MANUFACTURING

2 CELL MANUFACTURING

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2

The patient’s cryopreserved cells are shipped via specialized courier to an FDA-approved manufacturing facility, where the patient’s cells are genetically reprogrammed into CAR-T cells.1

CELL MANUFACTURING

3 INFUSION

3 INFUSION

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3

The patient may receive lymphodepleting chemotherapy to reduce the number of white blood cells and prepare the body for CAR-T cells. The patient receives their reprogrammed CAR-T cells during a single infusion, which can be administered in either an inpatient or outpatient setting at the hematologist’s discretion.1

INFUSION

4 MONITORING

4 MONITORING

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4

Monitor the patient 2 to 3 times during the first week after infusion. The patient should stay close to their treatment center for at least 4 weeks to monitor and be treated for potential side effects. Routine long-term monitoring is recommended.1

MONITORING

After the infusion and the initial post-infusion monitoring period (at least 4 weeks), the patient may return to their medical team for ongoing monitoring and regular care appointments. Here are some materials to support patients with their follow-up care.

Download the CAR-T guide for healthcare professionalsDownload the CAR-T guide for healthcare professionals

Is CAR-T suitable for my pALL and DLBCL patients?

CONSIDERATIONS TO ENHANCE PATIENT OUTCOMES

Before CAR-T cell therapy, pediatric and young adult patients with relapsed or refractory pALL or DLBCL had limited treatment options, low survival rates, and poorer outcomes. For many patients, treatments such as chemotherapy and bone marrow transplant are insufficient in achieving remission.

Did you know that…

 Who-is-eli-for-car-t-image
~1 of 5 children relapse or are refractory

in response to treatment for B-cell ALL5,6,7

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~25% cannot achieve complete remission

after experiencing refractory or relapsed pALL8

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>30% failure rate

for frontline therapy diagnosed for DLBCL, the most common lymphoid cancer, and adults with refractory/ relapsed DLBCL9

 Who-is-eli-for-car-t-image
~1 in 3 relapse after CHOP

with alternative therapies needed for these DLBCL patients10, and nearly 50% of the refractory/relapsed DLBCL patient population have no effective standard of care treatment options11

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~50% of DLBCL patients relapse within 3 years

among all adult DLBCL patients who are eligible for transplant. Transplant also has a considerable risk of transplant related morbidity 12

Survival rates for those undergoing transplant:

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< 50% in DLBCL patients

in second or later remission (24-month survival rate) 12

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≤ 40% after allogeneic SCT in children

who were in their second or later remission (5-year survival rate) 13

However, medical breakthroughs and scientific advancements have improved the treatment landscape for pALL and DLBCL patients.

  • CAR-T cells have displayed a high level of efficacy in B cell malignancies, achieving up to a 90% complete remission rate in anti-CD19 CAR-T cells for B-cell ALL14
  • CAR T therapy has improved outcomes for patients with refractory/relapsed DLBCL, as compared to standard chemotherapy regimens. According to a meta-analysis published by Mubarak Al‑Mansour, Meteb Al‑Foheidi and Ezzeldin Ibrahim on 29 July 2020 in Molecular and Clinical Oncology, a study conducted among 306 patients with R/R DLBCL showed that outcomes were highly favorable with a complete remission mean rate of 46%15

Why should patients be referred early to a CAR-T expert?

Timely patient identification and referrals to CAR-T experts is critical for better patient outcomes. Data shows T cell health deteriorates over time and is associated with lower response rates to CAR-T therapies.16 To minimize the impact on T cell health, monitor and consider your patients for this treatment option when their T cells are relatively healthy. Chemotherapy and additional treatments impact T cell health over time, therefore referrals for apheresis should also be considered prior to giving therapies that may compromise the leukapheresis product.17

  • Consider collecting T cells early or before patients undergo many rounds of treatment
  • For optimal cell quality, consider leukapheresis before putting the patient through chemotherapy
  • Certain salvage drugs with long washout periods will significantly delay apheresis18

Which patients may be suitable
for CAR-T therapy?

PEDIATRIC B-CELL ACUTE LYMPHOBLASTIC LEUKEMIA

Pediatric and young adult patients up to and including 25 years of age with pediatric B-cell acute lymphoblastic leukemia (pALL) that is refractory, in relapse post-transplant or in second or later relapse19, which includes those who:

  • Have not gone into remission following frontline treatment (primary refractory)
  • Have relapsed and cannot achieve remission (chemorefractory)
  • Have had second or subsequent relapse following complete remission
  • Have relapsed following allogeneic SCT

DIFFUSE LARGE B-CELL
LYMPHOMA

Adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) after two or more lines of systemic therapy19, which includes patients who are/have:

  • Ineligible or not a candidate for autologous transplant therapy
  • Relapsed following autologous SCT
  • Transplant-intended but is currently unresponsive to salvage chemotherapy
  • Notable comorbidities (including organ dysfunction)
  • Refractory disease
  • High grade lymphoma

Note: Complete remission is not a requirement.

Getting started with CAR-T

Getting Start Image

CAR-T cell therapy is available at certified hospital sites around the globe and reimbursed in many markets. Patients seeking to receive treatment may be required to travel.

CAR-T therapy may be associated with certain risks such as cytokine release syndrome (CRS) and neurological toxicities, which may be severe or life-threatening. Please refer to the Prescribing Information for more details.

Getting Start Image

References

  1. https://www.hcp.novartis.com/products/kymriah/diffuse-large-b-cell-lymphoma-adults/treatment-process/ (8/21 138566) – extracted from Novartis resource

  2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4861363/; Maus MV, Levine BL. Oncologist. 2016; 21:608-617

  3. Kawalekar OU, O’Connor RS, Fraietta JA, et al. Immunity. 2016;44:380-390

  4. Porter DL, Hwang WT, Frey NV, et al. Sci Transl Med. 2015;7:303ra139. doi:10.1126/scitranslmed.aac5415.

  5. Eissa HM et al. Blood Cancer J. 2017;7(2):e531

  6. Locatelli F et al. Blood. 2012;120(14):2807-2816.

  7. Ko RH et al. J Clin Oncol. 2010;28(4):648-654.

  8. Schrappe M et al. N Engl J Med. 2012;366(15):1371-1381.

  9. Crump M et al. Blood 2017;130:1800–8

  10. Harris LJ, Patel K, Martin M. Novel Therapies for Relapsed or Refractory Diffuse Large B-Cell Lymphoma. Int J Mol Sci. 2020;21(22):8553. Published 2020 Nov 13. doi:10.3390/ijms21228553

  11. Karlovitch, S. (2021, October 12). Newer agents for DLBCL show potential for earlier use in the course of treatment. Targeted Oncology. Retrieved October 27, 2021, from https://www.targetedonc.com/view/newer-agents-for-dlbcl-show-potential-for-earlier-use-in-the-course-of-treatment.

  12. Friedberg JW. Hematology Am Soc Hematol Educ Program. 2011;2011:498-505.

  13. Bondarenko SN et al. CTT Journal. 2016;5(2):12-20.

  14. New development in CAR-T cell therapy. (2017). PubMed Central (PMC). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5320663/

  15. Efficacy and safety of second-generation CAR T-cell therapy in diffuse large B-cell lymphoma: A meta-analysis. (2020, October 1). PubMed Central (PMC). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7416618/

  16. Das RK et al. Cancer Discov. 2019;9(4):492-499

  17. Yakoub-Agha I, et al. Haematologica. 2020;105(2):297-316

  18. Jain T, et al. Biol Blood Marrow Transplant. 2019;25(12):2305-2321

  19. Kymriah [summary of product characteristics]. Nuremberg, Germany: Novartis Pharma GmbH; 2020.