Case Sharing Prof. Li Chen: Can Serinisol in the Treatment of Plasmablastic Lymphoma Reverse the Outcomes of Multidrug-Refractory Patients?

Plasmablastic lymphoma (PBL) is a rare and aggressive subtype of non-Hodgkin's lymphoma (NHL), due to its special morphological and immunophenotypic features, chemotherapy resistance, and clinical features with a high recurrence rate , treatment is extremely challenging and the patient's overall prognosis is poor
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At present, there is no standard treatment plan for PBL, and the NCCN guidelines recommend the use of intensive chemotherapy
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In recent years, with the application of proteasome inhibitors (PI), immunomodulatory agents (IMiD) and autologous hematopoietic stem cell transplantation (ASCT), the survival prognosis of some PBL patients has been improved, but some patients with refractory PBL still face the Drug resistance and disease relapse are urgently needed to induce remission in patients with novel mechanisms of action
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High expression of nuclear export protein 1 (XPO1) plays an important role in tumor disease progression and is associated with poor patient prognosis.
Selinexor is the world's first approved oral XPO1 selective nuclear export inhibitor SINE, based on its new mechanism of action, breaks through traditional targeting, and has shown good anti-tumor activity and safety in multiple clinical studies, bringing a brand new opportunity to patients with relapsed and refractory (R/R) PBL valid choice
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On this occasion, Yimaitong specially invited Professor Yao Yonghua from Shidong Hospital, Yangpu District, Shanghai to share the case experience of Selinesol in the treatment of PBL, and Professor Chen Li of Shanghai Changhai Hospital commented on the case! A patient with PBL, male, 25 years old, with no special medical history, the patient reported bloodshot in the snot and swelling of the skin around the nose for 2 months, and the CT scan of the sinus at the local hospital showed "sinusitis", and the nasal cavity was performed on March 6, 2021.
Endoscopic sinus fenestration, submucosal resection of the nasal septum and resection of sinus lesions for the whole group
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On March 19, 2021, postoperative pathological tips: plasmablastic lymphoma
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Baseline characteristics of the patient: Physical examination: the left palpebral fissure was narrowed, and a mass was seen on the left face, which was firm and without obvious tenderness
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Immunohistochemistry: CD20 (-), CyclinD1 (-), Ki67 (60%+), CD3 (-), EBER (+/-), CD79a (-), CD138 (+), Vs38c (minor +), CD56 (-), CD30 (-), EMA (-), kappa (-), Lambda (partial +), Desmin (-), HMB45 (-), Syn (-), S100 (-)
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PET/CT: soft tissue mass in the left maxillary sinus and left ethmoid sinus, increased glucose metabolism (SUVmax=15.
96), consistent with lymphoma manifestations, bilateral submandibular lymph nodes with increased glucose metabolism, considering the possibility of infiltration, the third, left inferior posterior mediastinum 8 The thoracic paravertebral nodule has increased glucose metabolism (SUVmax=5.
56).
Considering the possibility of lymphoma infiltration, the local flaky metabolism in the bone marrow cavity of the right femur is increased, and the right lower lobe pleural nodule has no abnormal increase in glucose metabolism.
Follow-up is recommended
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Bone marrow morphology: hematopoietic cells were generally normal, and 1.
4% plasma cells were seen in the bone marrow
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Clinical diagnosis: Plasmablastic lymphoma stage IIA, IPI score 0 first-line therapy April 2021 to May 2021 Bortezomib combined with CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) Scheme, a total of 2 courses, second-line treatment of disease progression June 2021 Bortezomib combined with HyperCVAD (high-dose cyclophosphamide, vincristine, doxorubicin and dexamethasone) scheme, a total of 1 course, third-line treatment of disease progression 2021 In July, 2019, radiotherapy, bortezomib combined with CHOP chemotherapy, a total of 1 course, the disease progression and the efficacy of previous regimens were summarized.
The patient had previously experienced third-line treatment, and the conventional chemotherapy and radiotherapy failed to achieve remission, and the disease progressed rapidly.
Fourth-line treatment August 27, 2021 Combined with the patient's medical history and examination results, the combination of selinesol and GDP (gemcitabine, cisplatin, and dexamethasone) regimen was considered
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Imaging data: After 2 weeks of treatment with serinesole, bilateral deep superior neck space, right axilla, main pulmonary artery window, left prephrenic group, left diaphragmatic crura, left adrenal region, and lesser curvature of stomach.
, retroperitoneal around the abdominal aorta, multiple subcutaneous soft tissue nodules of different sizes, left ninth rib, right iliac bone and left sciatic bone, and bilateral pleura lesions were significantly smaller than the control in the previous film , FDG metabolism was reduced, and the efficacy was evaluated as partial remission (PR)
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On September 24, 2021, ASCT was performed on October 28, 2021.
On October 28, 2021, no obvious space-occupying lesions were found on multi-site CT scan After combined treatment with linisole, the lesions were significantly reduced, PR was obtained, and the safety was good
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Professor Yao Yonghua's diagnosis and treatment experience the difficulties in diagnosis and treatment of this patient: plasmablastic lymphoma stage IIA, IPI score of 0 points, received 3 lines of treatment and no remission in the past, and the disease progressed rapidly
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Combined with the patient's medical history and examination results, after 2 weeks of treatment with Selinesol combined with GDP regimen, the patient's multiple lesions were significantly reduced, FDG metabolism was reduced, and the efficacy evaluation was PR.
No obvious space-occupying lesions were found on plain scan, and the patient benefited significantly
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Selinesol is a drug targeting XPO1, which specifically inhibits XPO1 in a slow and reversible manner.
Based on its new mechanism of action, it helps to improve the remission rate and prolong the survival of patients
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This case suggests that for patients with PBL refractory to multi-line therapy and patients who are planning to undergo ASCT, the treatment plan containing selinenisol can help reduce tumor burden, improve the remission rate of patients, and provide guarantee for subsequent ASCT treatment
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Professor Chen Li commented that PBL is a rare and highly aggressive subtype of NHL in clinical practice, which mainly occurs in people with viral infection and immunodeficiency
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Its morphological manifestations are diffuse proliferation of large tumor cells resembling immunoblasts, with clinical features of early recurrence and chemotherapy resistance, and the overall prognosis of patients is poor
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At present, no standard treatment plan has been established for PBL, and high-dose multi-drug combination chemotherapy is the main clinical treatment plan
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For chemotherapy-resistant and recurrent patients, there is a lack of effective treatment options
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Selinesol is the world's first oral selective nuclear export inhibitor targeting a novel mechanism of tumor therapy, and exerts its unique anti-tumor activity mediated by multiple pathways: first, inhibiting XPO1, promoting tumor suppressor protein and other growth regulatory proteins.
Retention and activation in the nucleus; at the same time, it promotes the retention of oncogene mRNA in the nucleus and reduces the level of oncogenic proteins in the cytoplasm; and can restore hormone sensitivity by activating the GR pathway
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Based on its unique mechanism of action, in addition to being used as a single drug, selinesol can also be used in combination with multiple other drugs to improve the efficacy and deepen the depth of remission in patients
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The patient in this case belongs to refractory PBL.
He has previously received 3rd-line treatment, and was given multi-drug combined chemotherapy such as PI, but none of them has been effectively relieved, the clinical symptoms have not improved, and the disease progresses rapidly
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After the combination therapy with selenisol, the patient's multiple lesions were significantly reduced, FDG metabolism was reduced, and the efficacy evaluation reached PR, which provided a strong guarantee for the subsequent ASCT treatment, and helped the patient achieve deeper disease remission and long-term survival
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Compared with conventional chemotherapy regimens, the Selinexor combination regimen helps patients achieve remission faster and more effectively, provides a powerful weapon for R/R PBL patients who have failed multi-line therapy, and reverses the poor outcome of patient treatment! Professor Yao Yonghua, Chief Physician, MD, Chief Physician, Department of Hematology, Shidong Hospital, Yangpu District, Shanghai, Member, Hematology Branch, Chinese Association of Traditional Chinese Medicine, Member, Hematology Branch, Shanghai Medical Association, Member, Hematology Professional Committee, Shanghai Association of Integrative Medicine, Shanghai Medical Association, Department of Hematology Member of the Physician Branch Member of the Shanghai Hematology Department Clinical Quality Control Expert Committee Member of the Shanghai Society of Immunology Hematology and Immunity Professional Committee Member of the Shanghai Anti-Cancer Association Hematology and Tumor Professional Committee Professor Chen Li, editorial board member of Translational Medicine (Electronic) Journal, Chief Physician and Associate Professor, Master's tutor The chief physician of the Department of Hematology of Shanghai Changhai Hospital presided over the completion of the general project of the National Natural Science Foundation of China, the general scientific research project of the army's logistics, the general project of the scientific research fund of the Shanghai Science and Technology Commission, the science and technology development fund project of the Shanghai Municipal Health Bureau and the Shanghai Municipal Science and Technology Development Fund project.
A total of 7 key projects of the Science and Technology Committee have participated in the completion of more than ten major projects of the National Natural Science Foundation of China and major basic projects in Shanghai.
Published 120 papers; 35 first and corresponding authors, of which 7 SCI papers were completed as the first People have won one third prize for military medical achievements; one second prize for Shanghai Medical Science and Technology and one second prize for military medical achievements, 1 Shanghai scientific and technological achievement, and 1 national invention patent authorization.
The school is an advanced individual in teaching, presided over and completed 1 key project of the school-level education reform fund, edited 1 textbook, and participated in editing 6 textbooks.
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