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Selinisol is the world's first potent, oral nuclear output protein inhibitor with a unique mechanism of action and multiple signaling pathways, which can synergistically enhance the anti-tumor activity
of other drugs.
In December 2021, China's National Medical Products Administration (NMPA) approved that celinisol (trade name: Chevio ®) can be used in combination with dexamethasone to treat relapsed refractory multiple myeloma (R/R MM)
that has been previously treated and refractory to at least one proteasome inhibitor, an immunomodulator, and an anti-CD38 monoclonal antibody 。 Recently, the Expert Consensus on the Clinical Application of Selinisol in Multiple Myeloma (2022) (hereinafter referred to as the "Consensus") led by the Plasma Cell Disease Group of the Hematology Branch of the Chinese Medical Association was officially released, aiming to provide Chinese clinicians with medication reference
.
On this occasion, Yimaitong specially invited Professor Wu Depei from the First Affiliated Hospital of Soochow University, Professor Hu Yu from the Union Medical College Affiliated to Tongji Medical College of Huazhong University of Science and Technology, and Professor Li Juan from the First Affiliated Hospital of Sun Yat-sen University to interpret
the consensus from the aspects of the mechanism of action of Selinisole, standardized treatment recommendations and management of adverse events.
Without avoiding hardships, Seliniso faces the current situation and challenges of MM treatment
MM is the second most common malignancy of the hematological system, accounting for about 10%
of hematological malignancies.
According to 2020 statistics, there were 176404 new cases of MM worldwide and 117077 deaths
.
At present, the three new classes of drugs key to the treatment of MM are proteasome inhibitors (PIs), immunomodulators (IMiDs) and monoclonal antibodies (mAbs), although these three types of drugs have good efficacy for patients, but almost all patients will relapse in the course of the disease, MM is still incurable, so clinically there is an urgent need for drugs with different mechanisms of action to bring hope
to MM patients.
Selective nuclear output protein inhibitors (SINES) are considered a promising novel treatment, and Selinisole is a potent, oral XPO1 inhibitor that binds to the cargo-binding pocket Cys528 site in the XPO1 structure, reversibly blocking XPO1 activity
.
The mechanism of action of Seliniso against myeloma is mainly as follows: (1) to aggregate tumor suppressor proteins in the nucleus and then activate them to play anti-tumor effects; (2) Trap oncogene mRNA in the nucleus and reduce the level of oncogenic proteins in the cytoplasm; (3) Activate glucocorticoid receptor pathway and restore hormone sensitivity
.
In addition, the unique mechanism of action of Selinisol can also affect multiple signaling pathways, and cooperate with other drugs such as PIs and cytotoxic drugs to enhance anti-tumor activity and overcome drug
resistance.
No effort has been spared, and standardized medication of Selinisosol has brought clinical benefits to patients with MM
KEY REGISTERED CLINICAL STUDIES PUBLISHED IN THE MYELOMA FIELD INCLUDE PHASE II STORM, MARCH (CHINA) AND PHASE III BOSTON STUDIES, ALL OF WHICH HAVE SHOWN GOOD EFFICACY AND SAFETY OF CELINISOL AND HAVE BEEN APPROVED BY
THE FDA AND NMPA.
In addition, the Selinisod-based combination regimen has been included in the treatment recommendations of R/R MM in several domestic and international guidelines (see Table 1).
Based on the BOSTON study and some STOMP studies, SVd, SDd, SKd and other regimens have obvious benefits when applied to patients with first-time relapsed MM, so they are included in the first recurrence treatment recommendations
of domestic and foreign guidelines.
The expert group recommends the use of a 3-drug regimen based on Sd combined with other antimyeloma drugs for the treatment of patients with R/R MM, and the benefit of frontline relapse patients such as SVd, SKd, SPd, SDd, SRd, etc
.
will be more significant.
Clinicians can select the appropriate combination regimen
containing serinisol based on the patient's previous treatment, general condition, and disease status at relapse.
Table 1.
Seliniso is recommended in the guidelines for the diagnosis and treatment of MM at home and abroad
Selinisol combined with different antimyeloma drugs has done phase I dose climbing to obtain the corresponding RP2D
.
Regarding the selection of the starting dose of Selinisod, the expert group recommended the starting dose range of Selinisosol (see Table 2) with reference to RP2D in the combined regimen and combined with the therapeutic dose that patients can tolerate for long-term in clinical practice, for clinicians' reference, and will pay attention to more clinical research data and clinical practical application in the future
.
During the treatment of cerinisol, it is recommended that the initial dose be sufficient to minimize tumor burden
.
Timely dose adjustment rather than frequent or prolonged discontinuation may provide additional benefits
to patients.
Table 2.
Selinisosol dosage is recommended
Be confident, and the management of adverse reactions of Selinisole is under control
The most common adverse events of celinisol leading to dose adjustment or discontinuation of treatment are thrombocytopenia, neutropenia, and fatigue, especially when combined with myelosuppressive drugs such as IMiDs
.
Through active prevention and supportive treatment, timely dose adjustment, etc.
, as the treatment time is prolonged, the patient's tolerance will gradually improve
.
The occurrence of adverse events in Selinisole is mainly concentrated in the first 2 treatment cycles and should be closely monitored and monitored
.
It is recommended to monitor blood routine, blood chemistry (electrolytes), weight, etc.
weekly, and twice a
week in severe cases.
The treatment of nausea and vomiting is more important than treatment
.
Active anti-nausea and vomiting prevention is
recommended prior to administration.
Professor Wu Depei
In recent years, with the clinical application of PIs, IMiDs and mAb, the overall prognosis and survival of MM patients have been significantly improved, but with the increasing number of treatment options, how to reasonably select various new drugs according to the clinical characteristics of patients, formulate the best combination drug plan, and manage the complications of related drugs are all issues
that clinicians need to pay close attention to 。 This consensus describes the mechanism, efficacy and adverse event management of XPO1 inhibitor Selinisosol in patients with multiple myeloma, in terms of mechanism of action, Selinisosol has its unique mechanism, by affecting multiple signaling pathways, not only can exert direct anti-tumor activity, but also synergistically enhance the anti-tumor effect of other pathways, the dual mechanism of action for Selinisosol to improve the efficacy of patients, overcome drug resistance brings possibilities, and expects more MM patients to benefit from the new drug Selinisole
。
Yu Hu
As an incurable disease at present, most patients will eventually go to the dilemma of relapse and difficult treatment, facing problems such as limited treatment options and poor treatment effect, so new drugs are urgently needed to improve patient efficacy
.
As the world's first potent and oral nuclear output protein inhibitor, Selinisole has shown excellent efficacy in classic studies such as STORM, MARCH, BOSTON and STOMP, and Sd and SVd regimens have been approved, and SPd, SKd, SDd and other programs have also been recommended
by domestic and foreign guidelines.
In addition to bringing high response rate and prolonged PFS to patients with R/R MM who have received 1~3 lines of previous therapy, the combination regimen also provides significant benefits
for patients with MM such as frontline recurrence, carrying high-risk cytogenetic characteristics, refractory to lenalidomide, renal insufficiency, and the elderly.
This consensus summarizes the recommendations of domestic and foreign guidelines and the dosage of various celinisol combination regimens, and believes that with the continuous deepening of clinical research and the continuous promotion of real-world applications, this consensus can provide reference
for the majority of clinicians.
In addition, it is hoped that clinicians will continue to optimize treatment strategies according to the patient's own situation in the process of applying Selinisole, accumulate more clinical medication experience, and escort patients for deep remission and long-term survival!
Juan Li
With the launch of Selinisosol and its gradual practical application in clinical practice, clinicians should pay more attention to adverse reactions and their possible impact on patients' quality of life while paying attention
to patient efficacy.
Common hematological adverse reactions include thrombocytopenia and neutropenia during clinical use of Selinisole, and common non-hematological adverse reactions are nausea, vomiting, fatigue and fatigue, which can be improved
with supportive care.
Among them, for some adverse reactions such as nausea and vomiting, prevention is more important than treatment, and early active prevention is essential
to prevent the subsequent occurrence of nausea and vomiting.
Early intervention, close monitoring, and active management can be used as relevant principles for the management of adverse reactions in Selinisoleb, and this consensus lists in detail the management of common adverse events in the treatment of Selinisole, including adverse event grading, dose adjustment, and supportive treatment, hoping to provide a reference for clinicians, aiming to improve the safety and tolerability of patients treated with Selinisole, and lead MM patients to a brighter future!
Prof.
Depei Wu
Director of the Department of Hematology, Chief Physician, Professor, Doctoral Supervisor, The First Affiliated Hospital of Soochow University
Executive Deputy Director of the National Clinical Research Center for Hematological Diseases
Deputy Director of Jiangsu Hematology Institute
Director of the Institute of Hematopoietic Stem Cell Transplantation, Soochow University
Member of the 13th National Committee of the Chinese People's Political Consultative Conference
Chairman of the Hematology Branch of the Chinese Medical Association
Vice President of Hematologist Branch of Chinese Medical Doctor Association
Vice Chairman of the Expert Committee of China Hematopoietic Stem Cell Donor Database
Editor-in-Chief of Chinese Journal of Hematology
Prof.
Yu Hu
Member of the <>th National Committee of the Chinese People's Political Consultative Conference
Dean of Union Medical College Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology
Director of the Institute of Hematology, Huazhong University of Science and Technology
Recipient of the National Science Foundation for Outstanding Young Scholars
"Changjiang Scholar" Distinguished Professor
National Model Recipient of Teaching and Education
Winner of the second prize of National Science and Technology Progress Award
Winner of the National Innovation Medal
Ho Leung Ho Lee Foundation Award winner
Chairman-elect of Hematology Branch of Chinese Medical Association (Head of Thrombosis and Hemostasis Group)
Member of the Standing Committee of the Internal Medicine Branch of the Chinese Medical Association
Vice President of Hematologist Branch of Chinese Medical Doctor Association
Vice Chairman of the Experimental Hematology Society of the Chinese Society of Pathophysiology
Member of the Education Committee of the International Society for Thrombosis and Haemostasis
Chairman of the Hematology Branch of Hubei Medical Association
Editor-in-Chief of the Journal of Clinical Internal Medicine/Journal of Clinical Emergency
Associate Editor of Chinese Journal of Hematology/Journal of Clinical Hematology
Associate Editor of Chinese Journal of Hospital Management/Editorial Board Member of Chinese Journal of Hospital Management
Associate Editor of Thrombosis Research/Thrombosis and Haemostasis
Prof.
Juan Li
Second-level professor of Sun Yat-sen University, first-level chief physician, doctoral supervisor, famous doctor of Sun Yat-sen University
Director of the Institute of Hematology, Sun Yat-sen University, Director of the Department of Internal Medicine and Director of the Department of Hematology, The First Affiliated Hospital of Sun Yat-sen University
Chairman of Hematologist Branch of Guangdong Medical Association
Former Chairman of Hematology Branch of Guangdong Medical Association
Chairman of the Hematology Professional Committee of Guangdong Health Management Association
Vice President of Hematologist Branch of Chinese Medical Doctor Association, Vice Chairman of Multiple Myeloma Professional Committee
Member of the Standing Committee of the Hematology Branch of the Chinese Medical Association, leader of the Plasma Cell Disease Group
Vice Chairman of the Hematology Professional Committee of the Chinese Association of Women Doctors, the Hematology Professional Committee of the Cross-Strait Medical and Health Exchange Association, the Hematology Branch of the China Association for the Promotion of International Exchanges in Healthcare, and the Hematology Professional Committee of the China Medical Education Association
Member of the Standing Committee of the Hematology Branch of the Chinese Geriatrics Society
Member of the International Myeloma Society and the Asian Myeloma Network
He has presided over or is chairing more than 20 funds such as the National Natural Science Foundation, published more than 200 papers as the first author or corresponding author, more than 70 papers included in SCI, won the first and third prizes of Guangdong Province Science and Technology Progress Award, the second prize of the China Medical Award, and edited 7 monographs
as the first person in charge.
Note: Civio ® is the trade name
of Seliniso.
In December 2021, China's National Medical Products Administration (NMPA) approved Antengene's new drug application for Selinisol to treat previously treated relapsed or refractory multiple myeloma (R/R MM)
with at least one proteasome inhibitor, an immunomodulator, and an anti-CD38 monoclonal antibody in combination with dexamethasone.
In June 2020, the U.
S.
Food and Drug Administration (FDA) approved Selinisole for the treatment of patients with diffuse large B-cell lymphoma (DLBCL) above the third line; In addition, Seliniso is also approved in multiple countries for the treatment of patients with
relapsed and refractory DLBCL.
The content of the article is only for academic communication of medical and health professionals, if you are a non-medical and health professional, please take the initiative to exit browsing and reading, otherwise the related risks and consequences arising therefrom shall be borne
by yourself.
References:
Plasma Cell Disease Group, Hematology Branch of Chinese Medical Association.
Expert consensus on the clinical application of celinisol in multiple myeloma (2022).
Journal of Clinical Hematology.
2022, 35(9): 605-611.
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