Isatuximab

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Isatuximab
Isatuximab 4CMH.png
Isatuximab (pale blue) binding CD38 (purple). PDB: 4CMH ​
Monoclonal antibody
Type Whole antibody
Source Chimeric (mouse/human)
Target CD38
Clinical data
Trade names Sarclisa
Other namesSAR-650984, isatuximab-irfc
AHFS/Drugs.com Monograph
MedlinePlus a620023
License data
Pregnancy
category
Routes of
administration 		Intravenous
Drug class Antineoplastic
ATC code
Legal status
Legal status
Identifiers
CAS Number
DrugBank
ChemSpider
  • none
UNII
KEGG
Chemical and physical data
Formula C6456H9932N1700O2026S44
Molar mass 145190.99 g·mol−1

Isatuximab, sold under the brand name Sarclisa, is a monoclonal antibody (mAb) medication for the treatment of multiple myeloma. [6] [4]

Contents

The most common side effects include neutropenia (low levels of neutrophils, a type of white blood cell), infusion reactions, pneumonia (infection of the lungs), upper respiratory tract infection (such as nose and throat infections), diarrhoea and bronchitis (inflammation of the airways in the lungs). [4]

Isatuximab is an anti-CD38 mAb intended to treat relapsed or refractory multiple myeloma. [7] It entered in Phase II trials for multiple myeloma [8] and T-cell leukemia in 2015. [9] [ needs update ]

Medical uses

In the United States it is indicated, in combination with pomalidomide and dexamethasone (video about this from ASH 2022), for the treatment of adults with multiple myeloma who have received at least two prior therapies including lenalidomide and a proteasome inhibitor. [10] [11] [12] It is also indicated in combination with carfilzomib and dexamethasone, for the treatment of adults with relapsed or refractory multiple myeloma who have received one to three prior lines of therapy. [13] As of September 2024, it is also approved in combination with lenalidomide, bortezomib and dexamethasone for newly diagnosed patients inelibible for a hematopoietic stem cell transplantation. [14]

In the European Union it is indicated, in combination with pomalidomide and dexamethasone, for the treatment of adults with relapsed and refractory multiple myeloma (MM) who have received at least two prior therapies including lenalidomide and a proteasome inhibitor (PI) and have demonstrated disease progression on the last therapy. [4]

History

It was granted orphan drug designation for multiple myeloma by the European Medicines Agency (EMA) in April 2014, and by the U.S. Food and Drug Administration (FDA) in December 2016. [4] [15]

Researchers started a Phase I study with isatuximab in combination with pomalidomide and dexamethasone for the treatment of patients with multiple myeloma (MM). The results during the Phase I trial showed that 26 out of the 45 patients discontinued the treatment due to progression of the disease. The patients had already been heavily pretreated. The latter lead to a manageable safety profile where the dose of isatuximab in combination with pomalidomide and dexamethasone would be capped to the maximum of 10 mg/kg weekly every two weeks for future studies. [16]

Based on the remarkable findings during the Phase I trial, a Phase II trial was launched where researchers investigated isatuximab as a single agent in patients with MM. The heavily pretreated patients reacted well to the single administration of isatuximab during Phase II of the trial. [17]

A Phase III combination trial for plasma cell myeloma is comparing pomalidomide and dexamethasone with and without isatuximab is in progress with a completion date of 2021. [18]

Additionally, two Phase III trials were added in 2017. The first trial highlights whether there is an added value in the combination of isatuximab with bortezomib, lenalidomide and dexamethasone. The latter will be tested in patients with newly diagnosed MM who are not qualified for a transplant (IMROZ trial). The second trial evaluates the combinations of isatuximab with carfilzomib and dexamethasone compared to carfilzomib with dexamethasone. The second trial was designed for patients who were previously treated with one to three prior lines (IKEMA). There is currently[ when? ] no treatment for MM, however promising improvements have been made and the study is still ongoing. [19] [20]

In March 2020, it was approved for medical use in the United States. [10] [11] [12] [21]

The U.S. Food and Drug Administration (FDA) approved isatuximab-irfc in March 2020, based on evidence from a clinical trial (NCT02990338) of 307 subjects with previously treated multiple myeloma. [12] The trial was conducted at 102 sites in Europe, North America, Asia, Australia and New Zealand. [12]

The trial evaluated the efficacy and side effects of isatuximab-irfc in subjects with previously treated multiple myeloma. [12] Subjects were randomly assigned to receive either isatuximab-irfc (in combination with pomalidomide and low-dose dexamethasone) or active comparator (pomalidomide and low-dose dexamethasone). [12] Treatment was administered in both groups in 28-day cycles until disease progression or unacceptable toxicity. [12] Both subjects and health care providers knew which treatment was given. [12] The trial measured the time patients lived without the cancer growing (progression-free survival or PFS). [12]

It was approved for medical use in the European Union in May 2020. [4]

Structure and reactivity

The structure of isatuximab consists of two identical immunoglobulin kappa light chains and also two equal immunoglobulin gamma heavy chains. Chemically, isatuximab is similar to the structure and reactivity of daratumumab, hence both drugs show the same CD38 targeting. However, isatuximab shows a more potent inhibition of its ectozyme function. The latter gives potential for some non-cross reactivity. Isatuximab shows action of an allosteric antagonist with the inhibition of the CD38 enzymatic activity. Additionally, isatuximab shows potential where it can induce apoptosis without cross linking. [22] Lastly, Isatuximab reveals direct killing activity when a larger increase in apoptosis is detected in CD38 expressing cancer cells. Furthermore, isatuximab demonstrated a dose dependent inhibition of CD38 enzymatic activity. However, daratumumab with the same experimental conditions shows a more limited inhibition without a dose response. [23]

Reactions

Isatuximab binds uniquely to an epitope on the CD38 receptor and is the only CD38 antibody which can start apoptosis directly. [24] Isatuximab binds to a different CD38 epitope amino-acid sequence than does the anti-CD38 monoclonal antibody daratumumab. [25] The binding with the CD38 receptor is mainly via the gamma heavy chains and are more potent than other CD38 antibodies such as daratumumab which can inhibit the enzymatic activity of CD38. Moreover, isatuximab inhibits the hydrolase activity of CD38.[ medical citation needed ]

The antibodies show signs of improving antitumor immunity by eliminating regulatory T cells, B cells and myeloid-derived suppressor cells. The difference in binding between isatuximab and daratumumab is in the recognition of the different amino acid groups. Isatuximab identifies 23 amino acids of CD38 to the contrary with daratumumab who has 27. The residue of Glu233 has a flexible sidechain and faces the N-terminal of Asp1 residue in the isatuximab light chain. The latter light chain of isatuximab is also flexible which makes the interaction between CD38/Glu233 and the Asp1 weaker than the other interactions between CD38 and isatuximab. The caspase-dependent apoptotic pathway and the lysosomal mediated cell death pathway in MM cells is induced by isatuximab. The MM cell death follows the downstream reactions of the lysosomal activation. The latter also activates the production of reactive oxygen species. [26]

Available forms

Isatuximab or isatuximab-irfc is available as a drug in an intravenous infusion form. Injection doses are 100 mg/5 mL (20 mg/mL) solution in single-dose vial or 500 mg/25 mL (20 mg/mL) solution in single-dose vial. [6]

Mechanism of action

Cancer of the blood that is distinguished by an overproduction of malignant plasma cells in the bone marrow is called multiple myeloma. The myeloma cells are marked with uniformed overexpression of CD38 surface glycoproteins. Although these proteins are also expressed on other myeloid and lymphoid cells, the extent is relatively minor compared to myeloma cells. The fact that CD38 glycoproteins carry out various important cellular functions, and that they are plentiful on the surface of myeloma cells, has made them an appealing target for multiple myeloma treatment. [27] CD38 was first described as an activation marker, but later the molecule displayed functions in adhesion to endothelial CD31 proteins, e.g. as an aiding component of the synapse complex, as well as an ectoenzyme implicated in the metabolism of extracellular NAD+ and cytoplasmic NADP. The tumour cells can evade the immune system, possibly due to adenosine, an immunosuppressive molecule that arises as a product of the ectoenzymatic activity of CD38. [28]

Isatuximab-irfc is an IgG1-derived monoclonal antibody that selectively binds to the CD38 that exists on the exterior of hematopoietic and multiple myeloma cells (as well as other tumor cells). This drug induces apoptosis of tumor cells and activates immune effector mechanisms such as complement dependent cytotoxicity (CDC), antibody-dependent cellular phagocytosis (ADCP), and antibody-dependent cell-mediated cytotoxicity (ADCC). Isatuximab-irfc is able to stimulate natural killer (NK) cells in the absence of CD38-positive target tumor cells and blocks CD38-positive T-regulatory cells. [6] Furthermore, the NADase activity of CD38 is adjusted by isatuximab, similarly to other CD38 antibodies. Contrarily to daratumumab however, isatuximab can incite apoptosis directly without cross-linking, and in its binding epitope. [29] According to the FDA, isatuximab-irfc alone has reduced ADCC and direct tumor cell killing activity in vitro in comparison to when it is combined with pomalidomide. As well as increased anti-tumor activity as opposed to isatuximab-irfc or pomalidomide only in a human multiple myeloma xenograft model. [6]

Metabolism and toxicity

Metabolism

Isatuximab-irfc is likely to be metabolized through catabolic pathways into smaller peptides. When isatuximab is at a constant state it is expected that the ≥99% elimination will occur approximately two months after the last dose was administered. The clearance percentage diminished when the dosages were increased over time, as well as when multiple doses were administered. However, the elimination of isatuximab-irfc did not differ when applied as a single agent or as a combination therapy. [6]

Toxicity

A dose-limiting toxicity (DLT) has been characterized as the development of any of the following: grade ≥ 3 non-hematologic toxicity; grade 4 neutropenia or grade 4 thrombocytopenia lasting more than 5 days; grade ≥ 2 allergic reactions or hypersensitivity (i.e., infusion reactions); or any other toxicity considered to be dose-limiting by the investigators or sponsor. Grade ≤ 2 infusion reactions were excluded from the DLT definition, because, with suitable care, patients that had a grade 2 infusion reaction prior to completion of the infusion were able to finalize isatuximab administration. [29]

There is no recommended reduced dose of isatuximab-irfc. In the eventuality of hematological toxicity it may be necessary to delay administration so that the blood count may be recovered. [6] Although there is no counteracting agent for isatuximab, clinical experience with overdoses is seemingly nonexistent as well. Overdose symptoms will probably be in line with the side effects attached to isatuximab. Therefore, infusion reactions, gastrointestinal disturbances and an elevated risk of infections may occur. It is necessary to carefully monitor the patient in case of an overdose and to employ clinically indicated symptomatic and supportive procedures. [27]

No studies have been conducted with isatuximab concerning carcinogenicity, genotoxicity or fertility. [6]

Pregnancy

When given to pregnant women isatuximab-irfc can cause fetal injury, due to the mechanism of action. It can precipitate depletion of immune cells as well as decreased bone density in the fetus. Pregnant women are therefore notified of the potential risks to a fetus, and women that are able to reproduce are advised to use effective contraceptives during treatment and at least five months subsequent to the last dose of isatuximab-irfc.

Furthermore, it is not recommended to combine isatuximab-irfc with pomalidomide in women that are carrying a child, because pomalidomide may cause birth defects and death of the unborn child. [6]

Indications

Isatuximab is indicated as a CD38-directed cytolytic antibody. By inhibiting the enzymatic activity of CD38.

The binding of isatuximab to CD38 on multiple myeloma (MM) cells leads to a trigger to several mechanisms leading to direct apoptosis of target cancer cells. The triggered pathways are the caspase-dependent apoptotic and the lysosome-mediated cell death pathway in MM cells. [30]

It is used in a combination with dexamethasone and pomalidomide. The drug is thus to treat patients with multiple myeloma. Restrictions for the use of isatuximab is that the patients have to be adults who have at least received two previous treatments with lenalidomide and a proteasome inhibitor. [6]

Isatuximab is currently[ when? ] also being tested in a Phase II trial as a monotherapy against refractory/recurrent systemic light-chain amyloidosis. [30]

Efficacy and side effects

Efficacy

A Phase III study of patients with refractory and relapsed MM, who were resistant to lenalidomide and a proteasome inhibitor, and could not have received daratumumab, another anti-CD38 monoclonal antibody was published in 2019 (ICARIA-MM). The addition of isatuximab to pomalidomide and dexamethasone improved progression free survival to 11.5 months compared to 6.5 months, with an overall response rate of 63%. [31]

Side effects

Adverse reactions to isatuximab-irfc may include neutropenia, infusion-related reactions and/or secondary primary malignancies. [6] Of these three the most commonly occurring ones are the infusion-related reactions. [30] Examples of the most frequent symptoms of infusion-related reactions are dyspnea, cough, chills, and nausea, while the severest signs and symptoms included hypertension and dyspnea. [6]

Effects on animals

The activity of isatuximab has been researched in mouse tumor models. It has been proven that isatuximab leads to antitumor activity in MM cells. Furthermore, the combination of isatuximab and pomalidomide will lead to an extra enhanced antitumor activity in MM cells. Thus, pomalidomide in vivo and in vitro leads to an increase of the activity of isatuximab. [30]

Animal studies in reproduction toxicity have not yet been carried out. So, the risks of birth defects and miscarriage risks are unknown. [6]

Names

Isatuximab is the United States Adopted Name (USAN). [32]

It was developed by ImmunoGen and Sanofi-Aventis with the development name SAR-650984.[ citation needed ]

Related Research Articles

<span class="mw-page-title-main">Multiple myeloma</span> Cancer of plasma cells

Multiple myeloma (MM), also known as plasma cell myeloma and simply myeloma, is a cancer of plasma cells, a type of white blood cell that normally produces antibodies. Often, no symptoms are noticed initially. As it progresses, bone pain, anemia, renal insufficiency, and infections may occur. Complications may include hypercalcemia and amyloidosis.

<span class="mw-page-title-main">Lenalidomide</span> Pair of enantiomers

Lenalidomide, sold under the brand name Revlimid among others, is a medication used to treat multiple myeloma, smoldering myeloma, and myelodysplastic syndromes (MDS). For multiple myeloma, it is a first line treatment, and is given with dexamethasone. It is taken by mouth.

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

Bortezomib, sold under the brand name Velcade among others, is an anti-cancer medication used to treat multiple myeloma and mantle cell lymphoma. This includes multiple myeloma in those who have and have not previously received treatment. It is generally used together with other medications. It is given by injection.

Elotuzumab, sold under the brand name Empliciti, is a humanized IgG1 monoclonal antibody medication used in combination with lenalidomide and dexamethasone, for adults that have received 1 to 3 prior therapies for the treatment of multiple myeloma. It is also indicated for adult patients in combination with pomalidomide and dexamethasone, who have received 2 prior therapies including lenalidomide and a protease inhibitor. Administration of elotuzumab is done intravenously. Each intravenous injection of elotuzumab should be premedicated with dexamethasone, diphenhydramine, ranitidine and acetaminophen. It is being developed by Bristol Myers Squibb and AbbVie.

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

Pomalidomide, sold under the brand names Pomalyst and Imnovid, is an anti-cancer medication used for the treatment of multiple myeloma and AIDS-related Kaposi sarcoma.

Brentuximab vedotin, sold under the brand name Adcetris, is an antibody-drug conjugate medication used to treat relapsed or refractory Hodgkin lymphoma (HL) and systemic anaplastic large cell lymphoma (ALCL), a type of T cell non-Hodgkin lymphoma. It selectively targets tumor cells expressing the CD30 antigen, a defining marker of Hodgkin lymphoma and ALCL. The drug is being jointly marketed by Millennium Pharmaceuticals outside the US and by Seagen in the US.

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

Carfilzomib, sold under the brand name Kyprolis, is an anti-cancer medication acting as a selective proteasome inhibitor. Chemically, it is a tetrapeptide epoxyketone and an analog of epoxomicin. It was developed by Onyx Pharmaceuticals.

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

Indatuximab ravtansine (BT062) is an immunomodulator and antineoplastic antibody-drug conjugate.

<span class="mw-page-title-main">Daratumumab</span> Monoclonal antibody

Daratumumab, sold under the brand name Darzalex among others, is an anti-cancer monoclonal antibody medication. It binds to CD38, which is overexpressed in multiple myeloma cells. Daratumumab was originally developed by Genmab, but it is now being jointly developed by Genmab along with the Johnson & Johnson subsidiary Janssen Biotech, which acquired worldwide commercialization rights to the drug from Genmab.

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

Filanesib is a kinesin spindle protein (KIF11) inhibitor which has recently been proposed as a cancer treatment, specifically for multiple myeloma.

<span class="mw-page-title-main">Cereblon E3 ligase modulator</span> Class of immunomodulatory drugs

Cereblon E3 ligase modulators, also known as immunomodulatory imide drugs (IMiDs), are a class of immunomodulatory drugs containing an imide group. The IMiD class includes thalidomide and its analogues. These drugs may also be referred to as 'Cereblon modulators'. Cereblon (CRBN) is the protein targeted by this class of drugs.

MDX-1097 is a monoclonal antibody therapy that in 2023 has been assessed in a Phase IIb clinical trial in conjunction with lenalidomide and dexamethasone as a treatment for multiple myeloma, a type of white blood cell cancer. MDX-1097 was originally developed by scientists at Immune System Therapeutics Ltd. In 2015, Haemalogix Ltd acquired the rights to MDX-1097 and are taking it through clinical testing.

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

Ixazomib is a drug for the treatment of multiple myeloma, a type of white blood cell cancer, in combination with other drugs. It is taken by mouth in the form of capsules.

<span class="mw-page-title-main">Melphalan flufenamide</span> Alkylating type cancer drug

Melphalan flufenamide, sold under the brand names Pepaxto and Pepaxti, is an anticancer medication used to treat multiple myeloma.

<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.

Daratumumab/hyaluronidase, sold under the brand name Darzalex Faspro, is a fixed-dose combination medication for the treatment of adults with newly diagnosed or relapsed/refractory multiple myeloma. It is a combination of daratumumab and hyaluronidase. It is administered via subcutaneous injection.

Belantamab mafodotin, sold under the brand name Blenrep, is a monoclonal antibody conjugated with a cytotoxic agent for the treatment of relapsed and refractory multiple myeloma.

Teclistamab, sold under the brand name Tecvayli, is a human bispecific monoclonal antibody used for the treatment of relapsed and refractory multiple myeloma. It is a bispecific antibody that targets the CD3 receptor expressed on the surface of T-cells and B-cell maturation antigen (BCMA), which is expressed on the surface of malignant multiple myeloma B-lineage cells.

Talquetamab, sold under the brand name Talvey, is a humanized monoclonal antibody used for the treatment of multiple myeloma. It is a bispecific GPRC5D-directed CD3 T-cell engager. Talquetamab is a bispecific antibody against two targets: human CD3, a T-cell surface antigen, and human G-protein coupled receptor family C group 5 member D (GPRC5D), a tumor-associated antigen with potential antineoplastic activity. Talquetamab binds both targets, drawing the T cells close to the tumor cells, causing a cytotoxic T-lymphocyte response. It is being developed by Janssen Pharmaceuticals.

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

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References

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  2. ↑ "AusPAR: Isatuximab". Therapeutic Goods Administration (TGA). 27 May 2022. Archived from the original on 27 May 2022. Retrieved 12 June 2022.
  3. ↑ "Summary Basis of Decision (SBD) for Sarclisa". Health Canada. 23 October 2014. Archived from the original on 30 May 2022. Retrieved 29 May 2022.
  4. 1 2 3 4 5 6 "Sarclisa EPAR". European Medicines Agency (EMA). 24 March 2020. Archived from the original on 26 June 2020. Retrieved 25 June 2020. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  5. ↑ "Sarclisa Product information". Union Register of medicinal products. Retrieved 3 March 2023.
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  8. ↑ Martin T (2015). "A Dose Finding Phase II Trial of Isatuximab (SAR650984, Anti-CD38 mAb) As a Single Agent in Relapsed/Refractory Multiple Myeloma". Blood. 126 (23): 509. doi: 10.1182/blood.V126.23.509.509 .
  9. ↑ "Safety and Efficacy of Isatuximab in Lymphoblastic Leukemia". ClinicalTrials.gov. 8 January 2020. Archived from the original on 19 September 2020. Retrieved 4 March 2020.
  10. 1 2 "FDA approves isatuximab-irfc for multiple myeloma". U.S. Food and Drug Administration (FDA). 2 March 2020. Archived from the original on 5 March 2020. Retrieved 2 March 2020.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  11. 1 2 "FDA Approves New Therapy for Patients with Previously Treated Multiple Myeloma". U.S. Food and Drug Administration (FDA) (Press release). 2 March 2020. Archived from the original on 3 March 2020. Retrieved 4 March 2020.PD-icon.svg This article incorporates text from this source, which is in the public domain .
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  14. ↑ "FDA approves isatuximab-irfc with bortezomib, lenalidomide, and dexamethasone for newly diagnosed multiple myeloma". U.S. Food and Drug Administration . 20 September 2024. Archived from the original on 4 October 2024. Retrieved 14 November 2024.
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  17. ↑ Martin T (7 December 2015). "A Dose Finding Phase II Trial of Isatuximab (SAR650984, Anti-CD38 mAb) As a Single Agent in Relapsed/Refractory Multiple Myeloma". ASH. Archived from the original on 20 March 2020. Retrieved 20 March 2020.
  18. ↑ Facon T, Dimopoulos MA, Leleu XP, Beksac M, Pour L, Hajek R, et al. (June 2024). "Phase 3 study results of isatuximab, bortezomib, lenalidomide, and dexamethasone (Isa-VRd) versus VRd for transplant-ineligible patients with newly diagnosed multiple myeloma (IMROZ)". Journal of Clinical Oncology. 42 (16_suppl): 7500. doi:10.1200/JCO.2024.42.16_suppl.7500. ISSN   0732-183X.
  19. ↑ Orlowski RZ, Goldschmidt H, Cavo M, Martin TG, Paux G, Oprea C, et al. (20 May 2018). "Phase III (IMROZ) study design: Isatuximab plus bortezomib (V), lenalidomide (R), and dexamethasone (d) vs VRd in transplant-ineligible patients (pts) with newly diagnosed multiple myeloma (NDMM)". Journal of Clinical Oncology. 36 (15_suppl): TPS8055. doi:10.1200/JCO.2018.36.15_suppl.TPS8055.
  20. ↑ Moreau P, Dimopoulos MA, Yong K, Mikhael J, Risse ML, Asset G, et al. (January 2020). "Isatuximab plus carfilzomib/dexamethasone versus carfilzomib/dexamethasone in patients with relapsed/refractory multiple myeloma: IKEMA Phase III study design". Future Oncology. 16 (2): 4347–4358. doi: 10.2217/fon-2019-0431 . PMID   31833394.
  21. ↑ "Drug Approval Package: Sarclisa". U.S. Food and Drug Administration (FDA). 25 March 2020. Archived from the original on 11 April 2021. Retrieved 21 March 2021.
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  23. ↑ Martin T, Baz R, Benson DM, Lendvai N, Wolf J, Munster P, et al. (June 2017). "A phase 1b study of isatuximab plus lenalidomide and dexamethasone for relapsed/refractory multiple myeloma". Blood. 129 (25): 3294–3303. doi:10.1182/blood-2016-09-740787. PMC   5482100 . PMID   28483761.
  24. ↑ Martin TG, Corzo K, Chiron M (2019). "Therapeutic Opportunities with Pharmacological Inhibition of CD38 with Isatuximab". Cells . 8 (12): 1522. doi: 10.3390/cells8121522 . PMC   6953105 . PMID   31779273.
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  26. ↑ Martin TG, Corzo K, Chiron M, Velde HV, Abbadessa G, Campana F, et al. (November 2019). "Therapeutic Opportunities with Pharmacological Inhibition of CD38 with Isatuximab". Cells. 8 (12): 1522. doi: 10.3390/cells8121522 . PMC   6953105 . PMID   31779273.
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  28. ↑ Morandi F, Horenstein AL, Costa F, Giuliani N, Pistoia V, Malavasi F (28 November 2018). "CD38: A Target for Immunotherapeutic Approaches in Multiple Myeloma". Frontiers in Immunology. 9: 2722. doi: 10.3389/fimmu.2018.02722 . PMC   6279879 . PMID   30546360.
  29. 1 2 Martin T, Strickland S, Glenn M, Charpentier E, Guillemin H, Hsu K, et al. (March 2019). "Phase I trial of isatuximab monotherapy in the treatment of refractory multiple myeloma". Blood Cancer Journal. 9 (4): 41. doi:10.1038/s41408-019-0198-4. PMC   6440961 . PMID   30926770.
  30. 1 2 3 4 Martin TG, Corzo K, Chiron M, Velde HV, Abbadessa G, Campana F, et al. (November 2019). "Therapeutic Opportunities with Pharmacological Inhibition of CD38 with Isatuximab". Cells. 8 (12): 1522. doi: 10.3390/cells8121522 . PMC   6953105 . PMID   31779273.
  31. ↑ Attal M, Richardson PG, Rajkumar SV, San-Miguel J, Beksac M, Spicka I, et al. (December 2019). "Isatuximab plus pomalidomide and low-dose dexamethasone versus pomalidomide and low-dose dexamethasone in patients with relapsed and refractory multiple myeloma (ICARIA-MM): a randomised, multicentre, open-label, phase 3 study". Lancet. 394 (10214): 2096–2107. doi:10.1016/s0140-6736(19)32556-5. PMID   31735560. S2CID   208049235.
  32. ↑ Statement On A Nonproprietary Name Adopted By The USAN Council - Isatuximab, American Medical Association
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