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Mantle cell lymphoma

GtoPdb Disease Summaries

This section gives an overview of the disease, and where available shows the following:

  • Synonyms: Shows known synonyms for the disease.
  • Description: Gives a basic description/definition of the disease.
  • Database Link: External links to the same disease at the Disease Ontology, OMIM or Orphanet sites.
  • Immunopharmacology comments: General comments about the target's role in immunopharmacology, provided by GtoImmuPdb curators.
  • Associated with: Counts are displayed for the total targets the disease is associated with in GtoPdb. The counts of targets and ligands of immunological relevance associated to the disease are also shown.

More information can be found in the help pages.

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Disease ID:591
Name:Mantle cell lymphoma
Associated with:3 targets
3 immuno-relevant ligands
Description
MCL is an aggressive form of non-Hodgkin’s lymphoma (NHL; median survival of 3-4 years) that arises from B-cells originating within the mantle zone of lymphatic follicles. In the US, around six percent of all new NHL cases are MCL.
Database Links
Disease Ontology: DOID:0050746
Orphanet: ORPHA52416

Targets

GtoPdb Disease Summaries - Targets

Click on the target name to link to its detailed view page

Where available, information is display on the role of the target in the disease; drugs which target the disease and their therapeutic use and side-effects.

If there is mutation data curated in GtoPdb this is indicated, with a link back to the appropriate section on the target detailed view page

Immuno ligand interactions - If available, a table of immuno-relevant ligands is shown. These ligands have been curated as having an association to the disease and possess interaction data with the target in GtoPdb. The approval status of the ligand is shown, along with curator comments and an indication of whether the target is considered the primary target of the ligand.

More information can be found in the help pages.

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Key to terms and symbols
CCR7
References:  4
ATM serine/threonine kinase
regulator of G-protein signaling 13
References:  3

Ligands

GtoPdb Disease Summaries - Ligands

Click ligand name to view ligand summary page

  • Approved: If the ligand is an approved drug this is indicated, along with approval bodies.
  • Immuno: Immuno icon indicates the ligand is immuno-relevant

Click the arrow in the final column to expand comments

  • Immuno Disease Comments: Curatorial comments specifically added as part of GtoImmuPdb. They give more information on the association between the ligand and disease in the context of immunopharmacology.
  • Clinical Use: General clinical comments relating to the ligand and may not necessarily be specific to the disease in question. With hyperlink to more details on the ligand summary pages.
  • Bioactivty Comments: Curatorial comments specifically about the compounds biological activity - with hyperlink to more details on the ligand summary pages.

More information can be found in the help pages.

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Key to terms and symbols Click ligand name to view ligand summary Click column headers to sort
Ligand References Clinical and Disease comments
acalabrutinib 11
Immuno Disease Comments: Approved drug for MCL patients who have received at least one prior therapy.
Clinical Use: Having already received FDA Orphan Drug Designation and Breakthrough Therapy Designation for mantle cell lymphoma (MCL: a rare and fast-growing type of non-Hodgkin lymphoma), in August 2017 the FDA granted priority review for acalabrutinib's New Drug Application (NDA), based on results from a Phase 2 study in relapsed/refractory MCL (NCT02213926). This resulted in full FDA approval in October 2017 (link to FDA announcement). This approval is for the treatment of MCL patients who have received at least one prior therapy.

For a list of all registered acalabrutinib trials, link here to ClinicalTrials.gov.

In November 2019, FDA approval was expanded to include treatment of CLL or SLL, following evaluation in trials including NCT02475681 and NCT02970318; clinial trial results in patients with CLL are reported in [5], [2] and [1].

Trials to assess acalabrutinib's efficacy in a variety of solid tumours (such as bladder, prostate and non-small cell lung cancers) are ongoing.

In the European Union, the EMA has granted acalabrutinib orphan designation for three rare diseases (as of 2016): CLL/SLL, lymphoplasmacytic lymphoma and MCL.

SARS-CoV-2 and COVID-19: In response to the SARS-CoV-2 pandemic acalabrutinib was evaluated in COVID-19 patients, as part of the UK's Accelerating COVID-19 Research and Development (ACCORD) initiative (June 2020). ACCORD is designed to fast-track potential treatments for COVID-19 through early-stage clinical trials [8]. In this setting researchers would aimed to determine if the anti-inflammatory action of BTK-inhibition has efficacy to reduce mortality in patients with severe COVID-19. In November 2020, AstraZeneca announced that acalabrutinib missed its primary endpoint in Phase 2, and failed to "increase the proportion of patients who remained alive and free of respiratory failure". | View clinical data
Bioactivity Comments: Acalabrutinib has improved selectivity, pharmacologic features (rapid oral absorption, favourable plasma exposure and a short half-life for example) and in vivo target coverage compared to the first generation BTK inhibitor, [2,10]. The IC50 values in the table below are for kinases that contain a cysteine residue aligning with Cysteine-481 in BTK (with exception of LYN). Unlike ibrutinib, acalabrutinib is devoid of activity across the SRC family kinases (IC50s > 1000 nM) [2]. | View biological activity
ibrutinib
Immuno Disease Comments: Approved drug for MCL.
Clinical Use: Ibrutinib is approved to treat patients with mantle cell lymphoma (MCL), a rare and aggressive type of leukemia, especially patients with MCL who have received at least one prior therapy. In Feb 2014 ibrutinib was granted US FDA approval for treating chronic lymphocytic leukemia (CLL), as with MCL, this is only indicated for patients who have received at least one prior therapy. In February 2015, the US FDA expanded approval to include the treatment of Waldenström's macroglobulinemia (WM), which is a form of type of non-Hodgkin's lymphoma. Approval was granted based on the outcome of clinical trial NCT01614821 which indicated that the drug can offer a substantial improvement over contemporary therapies.
In August 2017, the FDA expanded approval to include treatment of chronic graft versus host disease (cGVHD) after failure of one or more lines of systemic therapy (e.g. first-line corticosteroid therapy). This approval followed results from clinical trial NCT02195869. The recommended dose of ibrutinib for cGVHD is 420 mg, orally once daily. | View clinical data
zanubrutinib
Immuno Disease Comments: Approved drug for MCL (FDA 2019)
Clinical Use: Zanubrutinib was evaluated for efficacy in a large number of clinical trials, across a range of hematological cancers. Click here to link to ClinicalTrials.gov's full list of zanubrutinib/BGB-3111 studies.
The FDA first approved zanubrutinib in November 2019 for the treatment of mantle cell lymphoma (MCL; in adult patients who have received at least one prior therapy). In June 2020, the drug was approved in China for the treatment of adult patients with CLL/SLL who have received at least one prior therapy, and for patients with MCL who have received at least one prior therapy. In the EU, zanubrutinib holds orphan designation for lymphoplasmacytic lymphoma, which was granted in May 2019. In April 2021, the The FDA accepted a supplemental new drug application (sNDA) for zanubrutinib for the treatment of adults with Waldenström macroglobulinemia, and approval followed in August that year. FDA approval was expanded in early 2023, to include treatment of CLL, based on evidence from the phase 3 SEQUOIA study (NCT03336333) [6-7]. A further expansion by the FDA in March 2024 added the treatment of relapsed/refractory follicular lymphoma to zanubrutinib's indication list. | View clinical data
Bioactivity Comments: In a cellular assay, zanubrutinib inhibits BTK with an IC50 of 20nM [9]. | View biological activity

References

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1. Awan FT, Schuh A, Brown JR, Furman RR, Pagel JM, Hillmen P, Stephens DM, Woyach J, Bibikova E, Charuworn P et al.. (2019) Acalabrutinib monotherapy in patients with chronic lymphocytic leukemia who are intolerant to ibrutinib. Blood Adv, 3 (9): 1553-1562. [PMID:31088809]

2. Byrd JC, Harrington B, O'Brien S, Jones JA, Schuh A, Devereux S, Chaves J, Wierda WG, Awan FT, Brown JR et al.. (2016) Acalabrutinib (ACP-196) in Relapsed Chronic Lymphocytic Leukemia. N Engl J Med, 374 (4): 323-32. [PMID:26641137]

3. Islam TC, Asplund AC, Lindvall JM, Nygren L, Liden J, Kimby E, Christensson B, Smith CI, Sander B. (2003) High level of cannabinoid receptor 1, absence of regulator of G protein signalling 13 and differential expression of Cyclin D1 in mantle cell lymphoma. Leukemia, 17 (9): 1880-90. [PMID:12970790]

4. López-Giral S, Quintana NE, Cabrerizo M, Alfonso-Pérez M, Sala-Valdés M, De Soria VG, Fernández-Rañada JM, Fernández-Ruiz E, Muñoz C. (2004) Chemokine receptors that mediate B cell homing to secondary lymphoid tissues are highly expressed in B cell chronic lymphocytic leukemia and non-Hodgkin lymphomas with widespread nodular dissemination. J Leukoc Biol, 76 (2): 462-71. [PMID:15155773]

5. Sharman JP, Banerji V, Fogliatto LM, Herishanu Y, Munir T, Walewska R, Follows G, Karlsson K, Ghia P, Corbett G et al.. (2019) ELEVATE TN: Phase 3 Study of Acalabrutinib Combined with Obinutuzumab (O) or Alone Vs O Plus Chlorambucil (Clb) in Patients (Pts) with Treatment-Naive Chronic Lymphocytic Leukemia (CLL). Blood, 134 (Supplement_1): 31. [PMID:31724010]

6. Tam CS, Brown JR, Kahl BS, Ghia P, Giannopoulos K, Jurczak W, Šimkovič M, Shadman M, Österborg A, Laurenti L et al.. (2022) Zanubrutinib versus bendamustine and rituximab in untreated chronic lymphocytic leukaemia and small lymphocytic lymphoma (SEQUOIA): a randomised, controlled, phase 3 trial. Lancet Oncol, 23 (8): 1031-1043. [PMID:35810754]

7. Tam CS, Robak T, Ghia P, Kahl BS, Walker P, Janowski W, Simpson D, Shadman M, Ganly PS, Laurenti L et al.. (2020) Zanubrutinib monotherapy for patients with treatment naïve chronic lymphocytic leukemia and 17p deletion. Haematologica, 106 (9): 2354-2363. [PMID:33054121]

8. UK Department of Health and Social Care. COVID-19 treatments could be fast-tracked through new national clinical trial initiative. Accessed on 01/06/2020. Modified on 01/06/2020. gov.uk, https://www.gov.uk/government/news/covid-19-treatments-could-be-fast-tracked-through-new-national-clinical-trial-initiative

9. Wang Z, Guo Y. (2016) Substituted pyrazolo[1,5-a]pyrimidines as bruton's tyrosine kinase modulators. Patent number: US9447106B2. Assignee: Beigene Ltd.. Priority date: 25/04/2013. Publication date: 20/09/2016.

10. Wu J, Zhang M, Liu D. (2016) Acalabrutinib (ACP-196): a selective second-generation BTK inhibitor. J Hematol Oncol, 9: 21. [PMID:26957112]

11. FDA Approves Calquence. Accessed on 01/11/2017. Modified on 01/11/2017. www.drugs.com, https://www.drugs.com/newdrugs/fda-approves-calquence-acalabrutinib-adults-mantle-cell-lymphoma-4624.html?utm_source=ddc&utm_medium=email&utm_campaign=FDA+Approves+Calquence+%28acalabrutinib%29+for+Adults+with+Mantle+Cell+Lymphoma