Plasma-cell lymphoma (PBL) is a rare subtype of aggressive non-Hodgkin lymphoma (NHL) that is challenging to treat and has an overall poor prognosis due to its special morphological and immunophenotype characteristics, chemotherapy resistance, and clinical characteristics with high recurrence rates. There is currently no standard treatment regimen for PBL, and intensive treatment is recommended in the NCCN guidelines. In recent years, with the application of proteasome inhibitors (PI), immunomodulators (IMiDs) and autologous hematopoietic stem cell transplantation (ASCT), the survival prognosis of some patients with PBL has been improved, but there are still some refractory PBL patients facing primary resistance and disease recurrence, and the need for drugs with new mechanisms of action to induce patient remission.
The high expression of nuclear output protein 1 (XPO1) plays an important role in tumor disease progression, and is associated with poor prognosis of patients, selinexor, as the world's first approved oral XPO1 selective nuclear output inhibitor (SINE), based on its new mechanism of action, breakthrough in traditional targeting, has shown good anti-tumor activity and safety in a number of clinical studies, bringing a new and effective choice for patients with relapsed refractory (R/R) PBL.
On this occasion, Professor Yao Yonghua of Yangpu District Shidong Hospital in Shanghai specially invited Professor Yao Yonghua to share the case experience of Celineiso's treatment of PBL, and Professor Chen Li of Shanghai Changhai Hospital commented on the case!
An example of PBL
The patient, male, 25 years old, with no special history, complained of streaking in the nasal discharge and swelling of the skin paranasals in february, and was scanned by a ct scan of the sinuses in the local hospital indicating "sinusitis", and on March 6, 2021, he underwent rhinoscopic sinus fenestration, nasal septal submucosal resection, and sinus lesion resection.
Postoperative pathological prompt on March 19, 2021: plasma-gyroblastic lymphoma.
Patient baseline features:
- Physical examination: the left eyelid fissure is reduced, a lump is visible on the left side of the face, hard, and there is no obvious tenderness.
- Immunohistochemistry: CD20(-), CyclinD1 (-), Ki67 (60%+), CD3 (-), EBER (+/-), CD79a (-), CD138 (+), Vs38c (small amount of +), CD56(-), CD30 (-), EMA(-), kappa(-), Lambda (partial +), Desmin(-), HMB45(-), Syn(-), S100(-).
- PET/CT: soft tissue mass in the left maxillary sinus, left sieve sinus, increased glucose metabolism (SUVmax=15.96), consistent with lymphoma manifestations, bilateral submandibular glucose metabolism increased lymph nodes, considering infiltration possibility, left lower mediastinum 3rd and 8th thoracic parathovertebral nodular foci, increased glucose metabolism (SUVmax=5.56), considering the possibility of lymphoma infiltration, local flaky metabolism in the bone marrow cavity of the middle femur, small pleural nodules in the lower lobe of the right lung, no abnormal glucose metabolism increased, follow-up is recommended.
- Bone marrow morphology: hematopoietic cells are generally normal, and 1.4% of plasma cell bone marrow images can be seen.
Clinical diagnosis: plasma-cytoblastic lymphoma stage II.A, IPI score of 0
First-line treatment
- Bortezomib combined with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) regimen from April 2021 to May 2021, 2 courses, disease progression
Second-line treatment
- June 2021 bortezomib combined with HyperCVAD (high-dose cyclophosphamide, vincristine, doxorubicin, and dexamethasone) regimen, a total of 1 course, disease progression
Third-line treatment
- In July 2021, radiotherapy, bortezomib combined with CHOP chemotherapy, a total of 1 course, disease progression
Summary of the efficacy of previous protocols
The patient has undergone third-line treatment in the past, but has not been relieved by conventional chemotherapy and radiotherapy, and the disease has progressed rapidly
Fourth-line treatment
- On August 27, 2021, taking into account the patient's medical history and examination results, celinesol plus GDP (gemcitabine, cisplatin, and dexamethasone) regimen was considered, and the dosing regimen was celinenisol 60 mg on days 1, 8, and 15.
Imaging Data:
After 2 weeks of treatment with Celineso, the bilateral deep superior cervical space, the right axilla, the main pulmonary window, the left anterior diaphragmatic group, the left diaphragmatic foot, the left adrenal region, the small curved side of the stomach, the peritoneal posterior abdominal aorta, the systemic subcutaneous multiple soft tissue small nodules of varying sizes, the left 9th rib, the right iliac bone and the left sciatic bone, and the pleura on both sides were significantly reduced compared with the previous film control, and the FDG metabolism was reduced, and the efficacy was evaluated as partial remission (PR).
- September 24, 2021 ASCT
- On October 28, 2021, there were no obvious mass lesions in multi-site CT scan
summary
The patient with PBL who received 3-line therapy had not achieved remission in the past, belonged to refractory PBL, and after giving 3 courses of celineiso combination therapy, the lesion was significantly reduced, PR was obtained and the safety was good, which was a good clinical practice for the treatment of PBL with the celineiso combination regimen.
Professor Yao Yonghua's diagnosis and treatment experience
- The patient's diagnosis and treatment difficulties: plasmablast lymphoma stage II.A, IPI score of 0 points, previously received 3-line treatment and has not remissioned, the disease progresses rapidly. Combined with the patient's medical history and examination results, after 2 weeks of treatment with Celineiso combined with GDP regimen, the patient's multiple lesions were significantly reduced, FDG metabolism was reduced, the efficacy was evaluated as PR, ASCT treatment was obtained after remission, and after 1 month, multi-site CT scan did not see obvious mass lesions, and the patient benefited significantly.
- Celineniso is a drug that targets XPO1 in a slow and reversible manner, specifically inhibiting XPO1, based on its entirely new mechanism of action, helping to improve patient response rates and prolong patient survival. This case suggests that for patients with multi-line treatment of refractory PBL and patients with proposed ASCT treatment, treatment regimens containing Celinesole can help reduce tumor burden, improve patient remission rate, and provide protection for subsequent treatment of ASCT.
Professor Chen Li commented
PBL is a clinically rare subtype of highly aggressive NHL that occurs primarily in viral infections and immunodeficiency populations. Its morphology is characterized by diffuse proliferation of large tumor cells similar to immunoblasts, with the clinical characteristics of early recurrence and chemotherapy resistance, and the overall prognosis of patients is poor. At present, PBL has not established a standard treatment regimen, and the clinical practice is mainly based on high-dose multi-drug combination chemotherapy regimens. For chemotherapy-resistant and recurrent patients, there is a lack of options for effective treatment options. Celineso is the world's first oral selective nuclear output inhibitor for a new mechanism of tumor therapy, which exerts its unique anti-tumor activity through multiple pathways: first, it inhibits XPO1, which promotes the intranuclear storage and activation of tumor suppressor proteins and other growth regulatory proteins; at the same time, promotes the retention of oncogene mRNA in the nucleus, reduces intracytoplasmic oncogenic protein levels; and restores hormone sensitivity by activating the GR pathway. Based on its unique mechanism of action, in addition to monotherapy, Selinisole can be combined with multiple other drugs to improve efficacy and deepen the depth of patient remission.
The patient in this case belonged to refractory PBL, who had previously received 3-line therapy and was given multi-drug combination chemotherapy regimens such as PI, but no effective remission was obtained, there was no improvement in clinical symptoms, and the disease progressed rapidly. After the administration of the celineiso combination therapy regimen, the patient's multiple lesions were significantly reduced, FDG metabolism was reduced, and the efficacy evaluation reached PR, which provided a strong guarantee for subsequent ASCT treatment and helped patients achieve deeper disease remission and long-term survival. Compared with conventional chemotherapy regimens, the combined Celineso regimen helps patients achieve remission faster and more effectively, providing a powerful weapon for patients with R/R PBL who have failed multi-line therapy, reversing the adverse outcomes of patient treatment!
Professor Yao Yonghua
- Director of the Department of Hematology, Shidong Hospital, Yangpu District, Shanghai
- Chief Physician, M.D
- Member of the Blood Disease Branch of the Chinese Association of Traditional Chinese Medicine
- Member of Hematology Branch of Shanghai Medical Association
- Member of the Hematology Committee of Shanghai Association of Integrative Traditional and Western Medicine
- Member of hematologist branch of Shanghai Medical Doctor Association
- Member of Shanghai Clinical Quality Control Expert Committee of Department of Hematology
- Member of the Blood Immunology Professional Committee of Shanghai Immunological Society
- Member of the Hematology and Tumor Professional Committee of Shanghai Anti-Cancer Association
- Member of the Editorial Board of the Journal of Translational Medicine (Electronics).
Professor Chen Li
- Chief physician, associate professor, master supervisor
- Chief Physician, Department of Hematology, Shanghai Changhai Hospital
- He has presided over the completion of 7 sub-projects of the National Natural Science Foundation of China, the logistics scientific research project of the whole army, the scientific research fund of the Shanghai Municipal Science and Technology Commission, the science and technology development fund project of the Shanghai Municipal Health Bureau and the key project of the Shanghai Municipal Science and Technology Commission
- He has participated in the completion of more than ten major projects of the National Natural Science Foundation of China and major basic projects in Shanghai
- He has published 120 papers, 35 first and corresponding authors, including 7 SCI papers
- As the first person to complete it, he won the third prize of the military medical achievements, the second prize of Shanghai Medical Science and Technology and the second prize of the military medical achievements, 1 Shanghai science and technology achievement, and 1 national invention patent authorization
- He has been rated as an advanced individual in hospital and school teaching for many times, presided over the completion of 1 key project of the school-level education reform fund, edited 1 textbook, and participated in the compilation of 6 textbooks