Comments from Professor Zhang Qingyuan of Case Sharing: Selinesol treatment broke the dilemma of relapse and refractory, and R/R DLBCL patients achieved complete remission!

Diffuse large B-cell lymphoma (DLBCL) is a highly aggressive and heterogeneous subtype of non-Hodgkin lympho.
With the application of R-CHOP (rituximab combined with cyclophosphamide, doxorubicin, vincristine, and prednisone) as the first-line standard treatment regimen, the survival prognosis of most DLBCL patients has improved1, However, there are still about 40% of patients with disease progression to relapsed/refractory (R/R) DLB.
How to effectively prolong the survival of these patients and improve the prognosis has become a hot topic of related research at home and abro.
High expression of nuclear export protein 1 (XPO1) plays an important role in the progression of DLBCL disease and is associated with poor patient prognos.
Selinexor (trade name: Sivio®) is the world's first approved oral XPO1 Selective inhibitor of nuclear export protein (SINE), by inhibiting XPO1, promotes the nuclear retention and activation of tumor suppressor proteins and other growth regulatory proteins, and down-regulates the levels of various oncogenic proteins in the cytoplasm, and induces tumor cell apoptos.
It has shown good antitumor activity and safety in multiple clinical studies, bringing new hope to R/R DLBCL patien.
On this occasion, Yimaitong specially invited Professor Wang Jingxuan of Harbin Medical University Affiliated Cancer Hospital to share the case experience of Celinisol in the treatment of DLB.
Professor Zhang Qingyuan of Harbin Medical University Affiliated Cancer Hospital commented on the case! A 40-year-old man with DLBCL complained of fibrosis around kidneys for half a year and retroperitoneal mass for half a mon.
He had a 3-year history of syphil.
In May 2018, he was found to have left peri-renal fibrosis by physical examinati.
He received hormone therapy in a foreign hospital for 1 month, and then took 10 mg of prednisone dai.
Baseline characteristics of the patient: Physical examination: no enlarged lymph nodes were found throughout the bo.
Imaging examination: On November 15, 2018, PET-CT in the other hospital showed: multiple lymph nodes in the abdominal cavity, retroperitoneum, posterior right septum, pelvic cavity and left retrogroin, space-occupying lesions in the tail of the pancreas, with increased glucose metabolism, lymph nod.
tumor possib.
Pathology report: On November 21, 2018, CT-guided biopsy showed that the morphology and immunoenzyme labeling of the left posterior abdominal cavity were consistent with diffuse large B-cell lymphoma, which was derived from germinal center B cel.
Immunohistochemistry: CK(-), Myo-D1(+), PAX-5(+), CD20(+), Bcl-6(+), CD21(+), ALK(-), CD10(+), CD3 (-), Ki67 index is about 9
Clinical diagnosis: first-line treatment of diffuse large B-cell lymphoma R-CHOP regimen on December 3, 2018, a total of 2 courses, radiotherapy for abdominal enlarged lymph nodes 5400cGy/27F; R-CHOP regimen on March 8, 2019, a total of 2 courses Course of treatment; PET-CT showed disease progression (PD) in December 201Second-line treatment January 4, 2020 R-ECHOP (R-CHOP combined with etoposide) regimen, a total of 3 courses; PET-CT showed PD on November 17, 202Summary of the efficacy of the previous regimens The patient had previously experienced 2-line therapy, and the conventional chemotherapy and radiotherapy failed to achieve remission, and the disease progress.
Baseline characteristics of patients in the screening period Baseline examination results: stage IV lymphoma, International Prognostic Index (IPI) score: 1 point Blood routine: white blood cell count 26x109/L, hemoglobin 152g/L, platelets 211x109/L on November 18, 2020 Biochemistry: creatinine 187umol/L on November 18, 2020, lactate dehydrogenase (LDH) 164umol/L, ALT 17U/L, AST 18U/L Imaging examination: CT on November 16, 2020: retroperitoneal lymphoma; Left nephropathy, considering lymphoma infiltration is not excluded; enlarged left supraclavicular lymph node; mildly dilated hydrops in the left renal pelvis and upper ureter; PET-CT on November 17, 2020: enlarged left supraclavicular lymph node with abnormal radioactive concentration , larger than before; multiple isodensity nodules were seen in the abdomen and pelvis, abnormal radioactive concentration, which increased and increased compared with the previous; left kidney mixed with soft tissue density mass shadow, showing highly abnormal radioactive concentration, increased compared with before, considering lymphatic Tumor-kidney infiltration is like.

The third-line treatment patients were screened and enrolled in the clinical trial (an open-label, single-arm clinical study of selenisole in the treatment of R/R DLBCL), and 13 cycles have been conduct.

Dosage: Take the medicine with meals on Mondays and Wednesdays, 60mg orally, once a day, take at least 120ml of warm water, do not crush or chew, and use antiemetic drugs in combinati.

Adverse reactions After about 7 weeks of medication, the patient developed double pneumonia, which may be related to the study dr.

The medication was suspended and symptomatic treatment was giv.

After 13 days, the medication was resumed without changing the drug do.

After about 37 weeks of medication, the patient's platelet count decreased by grade .

It may be related to the study drug, and symptomatic treatment should be given; the patients experienced increased ALT, AST and decreased white blood cell count during the treatment period, all of which were grade.

It was considered to be related to the study drug, and the dosage of the drug was not chang.

Efficacy evaluation After 7 weeks of treatment, the patient underwent retroperitoneal lymphoma re-examination, which was significantly smaller than before; left nephropathy, considering the possibility of lymphoma infiltration, was smaller than befo.
PET-CT: Abnormal radioactive concentrated lymph nodes in the left supralock, the volume was smaller than before, the degree of uptake was reduced, and the SUVmax was 8; the lesions of abnormal radioactive concentration in the abdominal cavity and pelvis were not shown, and changed after treatment; no abnormality was found in the left kidney Density and abnormal radioconcentration, changed after treatme.

After 48 weeks of treatment, there was no radioactive concentration in the left supraclavicular lymph node, 3 x 8 cm, and the metabolism disappeared, and the distribution of radioactivity in both kidneys showed no obvious abnormali.

Efficacy evaluation reached complete remission (CR)! It is concluded that the patient has not been relieved by 2-line therapy in the past, and achieved effective remission after monotherapy with selinex.

The best curative effect is CR, and it has good safe.

So far, 13 cycles of treatment have been completed, and the patient has achieved continuous remissi.

Professor Wang Jingxuan shared her medication experien.

The standard first-line treatment for DLBCL is R-CHOP, but about 40% of patients still experience relapse or refracto.

There is no standard treatment for R/R DLB.

The patient was ineffective after two-line treatment with R-CHOP and R-ECHOP, and participated in the clinical study of selinexor monothera.

He has been treated for 13 cycles, and the best efficacy evaluation reached .

Selenisole is an oral selective nuclear exportin inhibitor indicated for patients with DLBCL who have received at least 2 prior lines of thera.

Previous clinical data (SADAL study) showed that the overall response rate (ORR) in DLBCL patients with GCB subtype was 37% with selinisol monothera.

The pathological type of this case was DLBCL, CD20(+), CD10(+), which originated from germinal center B cells and was a GCB subty.

Therefore, the patient achieved sustained remission for a long time after treatme.
The patient's disease progressed after receiving 2-line standard treatment before, and extranodal organ kidney involvement occurr.

The biochemical report during the screening period showed abnormal creatinine (creatinine 180umol/L, mainly related to extranodal organ kidney involvemen.

Renal function did not continue to deteriorate during 1-year treatment with linisole monothera.

Previous studies have shown that selinisol has similar efficacy for different age groups or patients with different renal functi.

SADAL subgroup analysis showed that the median overall survival (OS) of patients with creatinine clearance less than 60ml/min The median OS of patients with >60ml/min was 1 months2, which is also the key to better curative effect in this patie.

No matter from the clinical data or the efficacy evaluation of the patients, it can be considered that selinesol has brought better survival hope for R/R DCBCL patien.

quality of life of patien.

Professor Zhang Qingyuan commented that XPO1 is responsible for the nuclear export of various proteins, including the nuclear export of tumor suppressor protei.

Overexpression of XPO1 will cause excessive nuclear export of tumor suppressor proteins, and the mRNA of oncogenic proteins will be transported to the cytoplasm to promote tumor cell grow.

associated with poor patient prognos.

The expression of XPO1 is higher in R/R DLBCL patients, and 60% of them have high expression of XPOSelinesol is the first oral small-molecule targeted drug approved by the.


Food and Drug Administration (FDA) as a monotherapy for DLB.

It inhibits the nuclear export function of XPO1, activates tumor suppressor proteins, and at the same time reduces cytoplasmic oncogenic protein mR.

level, exert anti-tumor effe.

Clinical studies have further confirmed the new and highly effective anti-tumor effect of selines.
The SADAL study is an international, multi-center, open-label phase II clinical study of selinexor monotherapy in R/R DLBCL patien.

A total of 134 patients were included for preliminary efficacy and safety analys.

The results showed that the ORR of all patients was 21 %, of which the ORR of patients who had previously received autologous hematopoietic stem cell transplantation (ASCT) was 45%; the median duration of response (DOR) was 3 months, and the median OS was 9 mont.

Based on this, selenisol has been approved by the FDA for the treatment of R/R DLBCL, and has been recommended by the NCCN guidelines for DLBCL patients who have received at least 2-line therapy (including disease progression after transplantation and CAR-T therap.

At the same time, related studies have shown that the mechanism of action of selinisol and a variety of chemotherapy and targeted drugs does not overlap and is synergistic, and the combined regimen has shown good efficacy and safety in the treatment of lymphoma With the deepening of research and the increase of clinical experience, it is believed that selinesol will bring better survival benefits to more R/R DLBCL patien.
Professor Wang Jingxuan Chief Physician, Professor and Doctoral Supervisor of Cancer Hospital Affiliated to Harbin Medical University Member of Breast Cancer Professional Youth Committee of China Anti-Cancer Association Member of China Cancer Rehabilitation and Palliative Youth Committee Vice Chairman of Breast Cancer Professional Committee of Heilongjiang Chronic Disease Association Beijing Cancer Prevention Society Member of the Standing Committee of the Professional Committee for Precise Targeted Diagnosis and Treatment of Breast Cancer Member of the Heilongjiang Provincial Breast Cancer Professional Youth Committee Member of the Lymphoma Branch of the Heilongjiang Provincial Medical Association Member of the Breast Disease Professional Committee of the Heilongjiang Provincial Medical Promotion Association Member of the Heilongjiang Provincial Medical Association Geriatric Cancer Branch Professor Zhang Qingyuan Chief Physician, Starlink Outstanding Professor, Doctoral Supervisor, Provincial Teaching Famous Teacher Director of Heilongjiang Cancer Prevention and Control Institute Vice President of the Cancer Hospital Affiliated to Harbin Medical University Leader of the National Key Specialty in Oncology Chairman-designate of the Lymphoma Professional Committee of the Association Vice-chairman of the Chemotherapy Professional Committee of the Chinese Anti-Cancer Association Projects, general projects, major new drug research and development projects of the Ministry of Science and Technology, international cooperation projects of the Ministry of Science and Technology, 863 projects and other major topi.

He has published more than 90 SCI articles as the corresponding author or the first author, and won 2 first-class awards for scientific and technological progress of the provincial governme.

He is the chief editor and deputy chief editor of many national standardized oncology textboo.

Note: Silvio® is the trade name of Selini.

In December 2021, China's National Medical Products Administration (NMPA) approved the New Drug Application for Antengene's selinisol, which is used in combination with dexamethasone to treat previously treated patients with at least one proteasome inhibitory effe.

Relapsed or Refractory Multiple Myeloma (R/R MM) Refractory to Anti-CD38 Monoclonal Antibo.

The above opinions are based on the clinical diagnosis experience of exper.

The cases involved in the article are teaching cases and have been anonymiz.

The content of the article is only for the academic exchange of medical and health professiona.

If you are a non-medical and health professional, please take the initiative to withdraw from browsing and reading, otherwise the related risks and consequences arising therefrom should be borne by yourse.
Reference: [1] Sehn LH, Salles.

Diffuse Large B-Cell Lympho.

N Engl J M.

2021;384(9):842-85 [2] Zijlstra JM, et .

The Association between Patient Characteristics and the Efficacy and Safety of Selinexor in Diffuse Large B-Cell Lymphoma in the SADAL Stu.

Cancers (Base.

2022 Feb 4;14(3):79 [3] Rosebeck S, et .

Synergistic Myeloma Cell Death via Novel Intracellular Activation of Caspase-10-Dependent Apoptosis by Carfilzomib and Selinex.

Mol Cancer Th.

2016 Jan;15(1):60-7 Edit: Irena Typesetting: XY Execution: Wenting Stamp “read the original text” to see more