Professor Xu Wei: Seliniso has contributed to improving the treatment status of DLBCL patients!

Pervasive large B-cell lymphoma (DLBCL) is a common subtype of highly aggressive and heterogeneous non-Hodgkin lymphoma that is more common in middle-aged and older people

Selinisol (trade name: Sivio ^®) is the world's first new mechanism of oral selective nuclear output protein inhibitor, based on good mechanism of action and clinical trial data, its treatment regimen has been approved by the U.

Professor Xu Wei

• Deputy Director of the Department of Hematology, First Affiliated Hospital of Nanjing Medical University (Jiangsu Provincial People's Hospital), doctoral supervisor

• Vice Chairman of the Hematology and Oncology Professional Committee of the Chinese Anti-Cancer Association, and leader of the lymphoma group

• Vice Chairman of the Lymphoma Professional Committee of the Chinese Geriatric Health Care Association

• Member of the Standing Committee of CSCO China Anti-Lymphoma Alliance

• Member of the Standing Committee of the Hematology Branch of the Chinese Geriatrics Society

• Member of the Standing Committee of the Hematology Committee of the Chinese Association of Women Physicians

• Member of the Standing Committee of the Lymphomatic Hematological Tumor Professional Committee of the Chinese Society of Geriatric Oncology

• Member of the Lymphoma Professional Committee of the Chinese Anti-Cancer Association

• He is a member of the Experimental Hematology Professional Committee of the Chinese Society of Pathophysiology

• He is a member and secretary of the Integrative Hematology Professional Committee of the Integrative Medicine Physicians Branch of the Chinese Medical Doctor Association

• Vice Chairman of the Hematology Society of Jiangsu Medical Association

• Vice President of Hematology Physician Branch of Jiangsu Medical Doctor Association

• He is the chairman of the Lymphoma Professional Committee of Jiangsu Research Hospital Association

• Chairman of Jiangsu Anti-Lymphoma Alliance

• Vice Chairman of the Hematology and Oncology Professional Committee of Jiangsu Anti-Cancer Association

• Member of the Standing Committee of the Lymphoma Professional Committee of Jiangsu Anti-Cancer Association

• Vice Chairman of Nanjing Hematology Society

• He is a member of the editorial boards of Chinese Journal of Hematology, Chinese Journal of Experimental Hematology, International Journal of Blood Transfusion and Hematology, Leukemia Lymphoma, and BLOOD Chinese Edition

Medical Pulse Pass: First of all, can you briefly introduce the current treatment status of DLBCL in China, and what are the treatment difficulties of DLBCL at present?

The continuous emergence of new drugs has enriched the treatment options of DLBCL patients and prolonged the survival of patients, but for some special or high-risk clinical subtypes of DLBCL, conventional treatment regimens have poor efficacy and poor prognosis

The SADAL study is an international, multi-centered, open-ended Phase 2b study designed to explore the efficacy and safety of Selinizol monotherapy in patients with R/R DLBCL, and has shown considerable efficacy in multiple clinical subgroups.

The results of the study showed that Selinisol was effective in patients with R/R DLBCL, with a total response rate (ORR) of 28% (95% CI 20.

Selinizol in patients with R/R DLBCL has controlled safety, and adverse events are mostly grade 1/2, and can be effectively managed
by supportive care or dose adjustment.

The most common grade 1/2 adverse events during treatment (TEAE) were nausea, fatigue, decreased appetite, and diarrhea, and the most common grade 3/4 TEAE were thrombocytopenia, neutropenia, and ^anemia4
.

Figure 1.
Tumor burden changes in all patients

Medical pulse communication: studies have shown that Selinizol has a prominent effect on CNS-affected DLBCL patients, the well-known hematology journal "Haematologica" has reported that a case of CNS-affected DLBCL patients after receiving Selinisol treatment, CNS lesions have shrunk significantly, please combine relevant research, talk about the efficacy and safety of Seliniso in the treatment of CNS-affected DLBCL patients?

The journal Haematologica published a Selinizol experience in the treatment of patients with refractory DLBCL with CNS involvement
.

The patient is a 55-year-old male patient who was diagnosed with DLBCL stage IIA in February 2011, with an International Prognosis Index (IPI) score of 0, GCB subtype, no expression of BCL-2, and weak expression of
MYC.

After previous 3-line therapy, 6 courses of R-CHOP regimen and 3 courses of R-ESHAP regimen were used in first-line and second-line therapy, and the best efficacy was CR, followed by autologous hematopoietic stem cell transplantation
.

After 7 months of second-line therapy, he was admitted to the hospital for the
development of clinical symptoms of CNS, including dysphagia and dysphonia due to paralysis.

After flow cytometry and cell analysis, clonal CD20 and CD10 lymphocytes appeared in the cerebrospinal fluid, so the three-line treatment
was started.

In the third-line therapy, the patient was given a salvage therapy with a high-dose intravenous methotrexate (HD-MTX) sheathed MTX, the patient did not respond to this treatment, and then joined the clinical trial, after 9 cycles of treatment, the patient developed left peripheral facial palsy, and MRI showed the presence of 2 lesions
in the CNS.

In the fourth-line therapy, the patient was given an oral 60 mg of Seliniso, BIW (d1, d3), and after 1 month of treatment, the patient's left side mass shrank by more than 50%, the right lesion completely regressed, and the cerebrospinal fluid was normal
.

After 5 months of treatment, MRI showed complete resolution
of the patient's brain lesions.

In terms of safety, patients with grade 3 fatigue and grade 2 anorexia during medication, supportive care and dose adjustment are given, and adverse reactions are well ^managed5
.

The patients in this case had DLBCL CNS recurrence/progression, usually this type of patient has a poor prognosis with an overall survival of less than 6 months, and the main cause of this type of adverse outcome is the lack of effective treatment
that can cross the blood-brain barrier.

Selinisol is the world's first approved oral selective nuclear output protein inhibitor (SINE) and has demonstrated good efficacy and safety
in a number of DLBCL clinical studies.

Clinical studies have shown that Selinizol can penetrate the blood-brain barrier and has antitumor activity
against central nervous system lymphoma.

The good efficacy of this patient after the application of Selinizol further confirms the above view
.

It is hoped that more CNS-related clinical data will be released in the future to bring more treatment options
for patients with CNS-refractory DLBCL.

Figure 2 AB: Selinizol before administration; CD: 1 month after the administration of Selinizol; After 5 months of administration of EF Selinizol

Medical Pulse Communication: Can you please combine your clinical experience in the use of the center to talk about the advantages of Selinizol in terms of efficacy and safety and its future clinical application prospects?

Selinizol is an inhibitor that targets nuclear output proteins 1 (XPO1) that mediate the transport of tumor suppressor and cancer-promoting proteins, are overexpressed in a variety of malignancies, and are associated
with poor patient prognosis.

As the world's first approved oral XPO1 inhibitor, Selinizol promotes the nuclear storage and activation of p53 and other tumor suppressor proteins and other growth regulators by inhibiting XPO-1 overexpression; Downregulate the levels of in-cytoplasmic proteins mRNA such as C-MYC and BCL-X; And activate the GR pathway, restore hormone sensitivity, induce apoptosis
of tumor cells with multiple mechanisms.

Selinizol has demonstrated good efficacy and safety in patients with R/R DLBCL in a number of clinical studies in the field of DLBL, such as the SEARCH study, the SELINDA study, and the XPORT-030 study^, based on the above, Selinisol has been approved by the FDA for the treatment of R/R DLBCL, and has been recommended by the NCCN guidelines for the third-line and above treatment of patients with R/R DLBCL6 ； In addition, in April 2022, Selinizol was recommended by the CSCO lymphoma guidelines for the treatment of R/R DLBCL⁷ with at least 2 relapses/progressions, opening up a new treatment option
for patients with DLBCL.

The future clinical application of Selinizol has broad prospects, and it can be explored
from the posterior line to the second line treatment, including the application of DLBCL patients with high-risk factors such as CNS involvement, EBV-positive, DHL, TP53 mutation, etc.

It is even possible to explore the use of Selinizol for first-line treatments, in combination with new treatment options, and new treatments, providing more patients with a wider range of treatment options
.

The continuous emergence of new drugs has enriched the treatment options of DLBCL patients and prolonged the survival of patients, but for DLBCL, which has high-risk factors such as CNS involvement, EBV positive, double strike, double expression and TP53 mutation, conventional treatment regimens have poor efficacy and poor patient prognosis, and there is no standard treatment plan to choose and use
.

Therefore, it is imperative
to improve the treatment effect of patients and improve the status quo of treatment.

Seliniso has shown broad application prospects in Chinese patients with R/R DLBCL and CNS-affected DLBCL, and it is worth further exploration to contribute to the continuous clinical benefits of patients!

Note: Sivio ^® is the trade name
of Seliniso.

In December 2021, China's State Drug Administration (NMPA) approved Deqi Pharmaceutical's Selinizol new drug marketing application to treat relapsed or refractory multiple myeloma (R/R MM) that has previously been treated with a proteasome inhibitor, an immunomodulator, and an anti-CD38 monoclonal antibody refractory to refractory multiple myeloma (R/R MM).

In June 2020, the U.
S.
Food and Drug Administration (FDA) approved Selinizol for the treatment of patients with third-line and above diffuse large B-cell lymphoma (DLBCL); In addition to this, Seliniso has been approved in several countries for the treatment of patients with
relapsed refractory DLBCL.

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References:

[1] Coiffier B,Sarkozy.
Diffuse large B-cell lymphoma: R-CHOP failure-what to do? [J].
Hematology Am Sor Hematol Educ Program, 2016, 2016(1): 366-378.

Chen Guangliang, et al.
Research progress of non-specific EBV-positive diffuse large B-cell lymphoma[J].
China Oncology,2022,32(3):258-267.

[3] Alaggio R,et al.
The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Lymphoid Neoplasms.
Leukemia.
2022 Jul; 36(7):1720-1748.

[4] Kalakonda N, et al.
Selinexor in patients with relapsed or refractory diffuse large B-cell lymphoma (SADAL): a single-arm, multinational, multicentre, open-label, phase 2 trial.
Lancet Haematol.
2020 Jul; 7(7):e511-e522.

[5] Bobillo S, et al.
Promising activity of selinexor in the treatment of a patient with refractory diffuse large B-cell lymphoma and central nervous system involvement.
Haematologica.
2018 Feb; 103(2):e92-e93.

[6] NCCN Clinical Practice Guidelines in Oncology for B-Cell Lymphomas.
2022 Version 2.

[7] Guidelines Working Committee of Chinese Society of Clinical Oncology.
Chinese Society of Clinical Oncology (CSCO) Guidelines for the Diagnosis and Treatment of Lymphoma 2022[M].
Beijing: People's Medical Publishing House, 2022.

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