Lisocabtagene maraleucel

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Lisocabtagene maraleucel
Gene therapy
Target gene CD19
Clinical data
Trade names Breyanzi
Other namesJCAR017, LM
AHFS/Drugs.com Monograph
MedlinePlus a621017
License data
Routes of
administration 		Intravenous
Drug class Antineoplastic
ATC code
Legal status
Legal status
Identifiers
DrugBank
UNII
KEGG
ChEMBL

Lisocabtagene maraleucel, sold under the brand name Breyanzi, is a cell-based gene therapy used to treat B-cell lymphoma. [3] [6]

Contents

Side effects include hypersensitivity reactions, serious infections, low blood cell counts, and a weakened immune system. [6] The most common side effects include decreases in neutrophils (a type of white blood cell that fights infections), in red blood cells or in blood platelets (components that help the blood to clot), as well as cytokine release syndrome (a potentially life-threatening condition that can cause fever, vomiting, shortness of breath, pain and low blood pressure) and tiredness. [4]

Lisocabtagene maraleucel, a chimeric antigen receptor (CAR) T cell (CAR-T) therapy, is the third gene therapy approved by the US Food and Drug Administration (FDA) for certain types of non-Hodgkin lymphoma, including diffuse large B-cell lymphoma (DLBCL). [6] Lisocabtagene maraleucel was approved for medical use in the United States in February 2021. [3] [6]

Medical uses

In the US, lisocabtagene maraleucel is indicated for the treatment of adults with large B-cell lymphoma (LBCL), including diffuse large B-cell lymphoma (DLBCL) not otherwise specified (including DLBCL arising from indolent lymphoma), high-grade B cell lymphoma, primary mediastinal large B-cell lymphoma, and follicular lymphoma grade 3B, who have refractory disease to first-line chemoimmunotherapy or relapse within 12 months of first-line chemoimmunotherapy; or disease to first-line chemoimmunotherapy or relapse after first-line chemoimmunotherapy and are not eligible for hematopoietic stem cell transplantation (HSCT) due to comorbidities or age; or relapsed or refractory disease after two or more lines of systemic therapy. [2] [3] [7] It is also indicated for adults with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who have received at least two prior lines of therapy, including a Bruton tyrosine kinase (BTK) inhibitor and a B-cell lymphoma 2 (BCL-2) inhibitor. [3]

In the EU, lisocabtagene maraleucel is indicated for the treatment of adults with diffuse large B-cell lymphoma (DLBCL), high grade B-cell lymphoma (HGBCL), primary mediastinal large B-cell lymphoma (PMBCL) and follicular lymphoma grade 3B (FL3B), who relapsed within 12 months from completion of, or are refractory to, first-line chemoimmunotherapy. [4]

Lisocabtagene maraleucel is not indicated for the treatment of people with primary central nervous system lymphoma. [3] [6]

Adverse effects

The FDA label carries a boxed warning for cytokine release syndrome (CRS), which is a systemic response to the activation and proliferation of CAR-T cells, causing high fever and flu-like symptoms and neurologic toxicities. [6]

In April 2024, the FDA label boxed warning was expanded to include T cell malignancies. [8]

History

Lisocabtagene maraleucel's safety and efficacy were established in a multicenter clinical trial of more than 250 adults with refractory or relapsed large B-cell lymphoma. [6] The complete remission rate after treatment was 54%. [6]

The FDA granted lisocabtagene maraleucel priority review, orphan drug, regenerative medicine advanced therapy (RMAT), and breakthrough therapy designations. [6] [9] Lisocabtagene maraleucel is the first regenerative medicine therapy with RMAT designation to be licensed by the FDA. [6] The FDA granted approval of Breyanzi to Juno Therapeutics Inc., a Bristol-Myers Squibb Company. [6]

Efficacy was evaluated in TRANSFORM (NCT03575351), a randomized, open-label, multicenter trial in adults with primary refractory LBCL or relapse within twelve months of achieving complete response (CR) to first-line therapy. [9] Participants had not yet received treatment for relapsed or refractory lymphoma and were potential candidates for autologous HSCT. [9] A total of 184 participants were randomized 1:1 to receive a single infusion of lisocabtagene maraleucel following fludarabine and cyclophosphamide lymphodepleting chemotherapy or to receive second-line standard therapy, consisting of three cycles of chemoimmunotherapy followed by high-dose therapy and autologous HSCT in participants who attained CR or partial response (PR). [9]

Efficacy was also evaluated in PILOT (NCT03483103), a single-arm, open-label, multicenter trial in transplant-ineligible patients with relapsed or refractory LBCL after one line of chemoimmunotherapy. [9] The study enrolled participants who were ineligible for high-dose therapy and HSCT due to organ function or age, but who had adequate organ function for CAR-T cell therapy. [9] Efficacy was based on CR rate and duration of response (DOR) as determined by an IRC. [9] Of 74 participants who underwent leukapheresis (median age, 73 years), 61 (82%) received lisocabtagene maraleucel of whom 54% (95% CI: 41, 67) achieved CR. [9] The median DOR was not reached (95% CI: 11.2 months, not reached) in participants who achieved CR and 2.1 months (95% CI: 1.4, 2.3) in participants with a best response of PR. [9] Among all leukapheresed participants, the CR rate was 46% (95% CI: 34, 58). [9]

Society and culture

In January 2022, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Breyanzi, intended for the treatment of adults with relapsed or refractory diffuse large B cell lymphoma (DLBCL), primary mediastinal large B-cell lymphoma (PMBCL) and follicular lymphoma grade 3B (FL3B), after at least two previous lines of treatments. [10] [11] The applicant for this medicinal product is Bristol-Myers Squibb Pharma EEIG. [10] Lisocabtagene maraleucel was approved for medical use in the European Union in April 2022. [4] [5]

Names

Lisocabtagene maraleucel is the international nonproprietary name (INN). [12]

Related Research Articles

In biology, chimeric antigen receptors (CARs)—also known as chimeric immunoreceptors, chimeric T cell receptors or artificial T cell receptors—are receptor proteins that have been engineered to give T cells the new ability to target a specific antigen. The receptors are chimeric in that they combine both antigen-binding and T cell activating functions into a single receptor.

<span class="mw-page-title-main">Diffuse large B-cell lymphoma</span> Type of blood cancer

Diffuse large B-cell lymphoma (DLBCL) is a cancer of B cells, a type of lymphocyte that is responsible for producing antibodies. It is the most common form of non-Hodgkin lymphoma among adults, with an annual incidence of 7–8 cases per 100,000 people per year in the US and UK. This cancer occurs primarily in older individuals, with a median age of diagnosis at ~70 years, although it can occur in young adults and, in rare cases, children. DLBCL can arise in virtually any part of the body and, depending on various factors, is often a very aggressive malignancy. The first sign of this illness is typically the observation of a rapidly growing mass or tissue infiltration that is sometimes associated with systemic B symptoms, e.g. fever, weight loss, and night sweats.

<span class="mw-page-title-main">Inotuzumab ozogamicin</span> Chemical compound

Inotuzumab ozogamicin, sold under the brand name Besponsa, is an antibody-drug conjugate medication used to treat relapsed or refractory B-cell precursor acute lymphoblastic leukemia. It is administered by intravenous infusion.

<span class="mw-page-title-main">Copanlisib</span> Chemical compound

Copanlisib, sold under the brand name Aliqopa, is a medication used for the treatment of adults experiencing relapsed follicular lymphoma who have received at least two prior systemic therapies.

Polatuzumab vedotin, sold under the brand name Polivy, is a CD79b-directed antibody-drug conjugate medication used for the treatment of diffuse large B-cell lymphoma (cancer). It was developed by the Genentech subsidiary of Roche.

<span class="mw-page-title-main">Juno Therapeutics</span> American biopharmaceutical company

Juno Therapeutics Inc was an American biopharmaceutical company founded in 2013 through a collaboration of the Fred Hutchinson Cancer Research Center, Memorial Sloan-Kettering Cancer Center and pediatrics partner Seattle Children's Research Institute. The company was launched with an initial investment of $120 million, with a remit to develop a pipeline of cancer immunotherapy drugs. The company raised $300 million through private funding and a further $265 million through their IPO.

<span class="mw-page-title-main">Venetoclax</span> Medication

Venetoclax, sold under the brand names Venclexta and Venclyxto, is a medication used to treat adults with chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), or acute myeloid leukemia (AML).

<span class="mw-page-title-main">Duvelisib</span> PI3K inhibitor

Duvelisib, sold under the brand name Copiktra, is a medication used to treat chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), and follicular lymphoma after other treatments have failed. It is taken by mouth. It is a PI3 kinase inhibitor.

Tisagenlecleucel, sold under the brand name Kymriah, is a CAR T cells medication for the treatment of B-cell acute lymphoblastic leukemia (ALL) which uses the body's own T cells to fight cancer.

Axicabtagene ciloleucel, sold under the brand name Yescarta, is a medication used for the treatment for large B-cell lymphoma that has failed conventional treatment. T cells are removed from a person with lymphoma and genetically engineered to produce a specific T-cell receptor. The resulting chimeric antigen receptor T cells (CAR-Ts) that react to the cancer are then given back to the person to populate the bone marrow. Axicabtagene treatment carries a risk for cytokine release syndrome (CRS) and neurological toxicities.

<span class="mw-page-title-main">Umbralisib</span> Chemical compound

Umbralisib, sold under the brand name Ukoniq, is an anti-cancer medication for the treatment of marginal zone lymphoma (MZL) and follicular lymphoma (FL). It is taken by mouth.

<span class="mw-page-title-main">Loncastuximab tesirine</span> Medication

Loncastuximab tesirine, sold under the brand name Zynlonta, is a monoclonal antibody conjugate medication used to treat large B-cell lymphoma and high-grade B-cell lymphoma. It is an antibody-drug conjugate (ADC) composed of a humanized antibody targeting the protein CD19.

<span class="mw-page-title-main">Selinexor</span> Anti-cancer drug

Selinexor sold under the brand name Xpovio among others, is a selective inhibitor of nuclear export used as an anti-cancer medication. It works by blocking the action of exportin 1 and thus blocking the transport of several proteins involved in cancer-cell growth from the cell nucleus to the cytoplasm, which ultimately arrests the cell cycle and leads to apoptosis. It is the first drug with this mechanism of action.

<span class="mw-page-title-main">Zanubrutinib</span> Chemical compound

Zanubrutinib, sold under the brand name Brukinsa, is an anticancer medication used for the treatment of mantle cell lymphoma (MCL), Waldenström's macroglobulinemia (WM), marginal zone lymphoma (MZL), and chronic lymphocytic leukemia (CLL). Zanubrutinib is classified as a Bruton's tyrosine kinase (BTK) inhibitor. It is given by mouth.

<span class="mw-page-title-main">Pemigatinib</span> Pharmaceutical drug

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Brexucabtagene autoleucel, sold under the brand name Tecartus, is a cell-based gene therapy medication for the treatment of mantle cell lymphoma (MCL) and acute lymphoblastic leukemia (ALL).

Tafasitamab, sold under the brand name Monjuvi, is a medication used in combination with lenalidomide for the treatment of adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL).

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References

  1. ↑ "Summary Basis of Decision - Breyanzi". Health Canada. 16 August 2022. Archived from the original on 29 September 2022. Retrieved 29 September 2022.
  2. 1 2 "Breyanzi- lisocabtagene maraleucel kit". DailyMed. Archived from the original on 24 March 2024. Retrieved 24 March 2024.
  3. 1 2 3 4 5 6 "Breyanzi (lisocabtagene maraleucel)". U.S. Food and Drug Administration (FDA). 13 November 2020. Archived from the original on 24 March 2024. Retrieved 24 March 2024.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  4. 1 2 3 4 "Breyanzi EPAR". European Medicines Agency. 24 January 2022. Archived from the original on 24 March 2024. Retrieved 24 March 2024. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  5. 1 2 "Breyanzi Product information". Union Register of medicinal products. Archived from the original on 4 March 2023. Retrieved 3 March 2023.
  6. 1 2 3 4 5 6 7 8 9 10 11 "FDA Approves New Treatment For Adults With Relapsed Or Refractory Large-B-Cell Lymphoma". U.S. Food and Drug Administration (FDA) (Press release). 5 February 2021. Archived from the original on 5 March 2022. Retrieved 5 February 2021.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  7. ↑ "FDA Roundup: March 15, 2024". U.S. Food and Drug Administration (FDA). 15 March 2024. Archived from the original on 16 March 2024. Retrieved 24 March 2024.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  8. ↑ "FDA Requires Boxed Warning for T cell Malignancies Following Treatment with BCMA-Directed or CD19-Directed Autologous Chimeric Antigen Receptor (CAR) T cell Immunotherapies". U.S. Food and Drug Administration (FDA). 18 April 2024. Archived from the original on 19 April 2024. Retrieved 19 April 2024.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  9. 1 2 3 4 5 6 7 8 9 10 "FDA approves lisocabtagene maraleucel". U.S. Food and Drug Administration. 27 June 2022. Archived from the original on 28 June 2022. Retrieved 28 June 2022.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  10. 1 2 "Breyanzi: Pending EC decision". European Medicines Agency (EMA). 28 January 2022. Archived from the original on 28 January 2022. Retrieved 28 January 2022. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  11. ↑ "New gene therapy treatment for patients with relapsed or refractory large B-cell lymphoma" (Press release). European Medicines Agency (EMA). 27 January 2022. Archived from the original on 28 January 2022. Retrieved 28 January 2022.
  12. ↑ World Health Organization (2019). "International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 81". WHO Drug Information. 33 (1): 82-3. hdl: 10665/330896 .
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