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"The 6th Anti-leukemia·Lymphoma International Summit Forum and CSCO Anti-leukemia Alliance & Anti-Lymphoma Alliance Tour Lecture-Harbin Station" will be held in Harbin on July 8-10, 2021 in a combined online and offline manner Hold
.
The conference was co-sponsored by the Chinese Society of Clinical Oncology (CSCO), CSCO Anti-Leukemia Alliance and CSCO Anti-Lymphoma Alliance, and co-organized by the Institute of Hematology and Oncology of Harbin First Hospital affiliated to Harbin Institute of Technology and Peking University Cancer Hospital
.
At the meeting, Professor Huang Wenrong from the Department of Hematology, the Fifth Medical Center of the PLA General Hospital gave a report on the topic of "Problems in the Treatment of Primary Central Nervous System Lymphoma (PCNSL)".
The editor organized the main content as follows for readers Reference
.
What is the appropriate induction chemotherapy for PCNSL patients? Professor Huang said that the complete remission (CR) rate of high-dose methotrexate (HD-MTX) treatment of PCNSL is relatively low, only 18%
.
Studies have explored the efficacy of ultra-high-dose MTX (8g/m2) combined with temozolomide in the treatment of PCNSL, and the CR rate is as high as 66%
.
So can the application of ultra-large doses of MTX alone improve the remission rate of PCNSL? The German multi-center prospective phase 2 study showed that the overall response rate (ORR) of the ultra-high-dose MTX treatment of PCNSL is higher, but the CR rate is only 26.
6%, and the high-dose MTX has more serious side effects
.
Therefore, some researchers have explored the application of HD-MTX combined with other programs in PCNSL.
The results of a prospective study in 24 centers in 6 European countries showed that HD-MTX combined with high-dose cytarabine significantly improved the remission rate of PCNSL (ORR is 70%, CR rate is 46%), but it also significantly increases side effects
.
Later, Professor Huang introduced that in the IELSG32 study, the MATRix induction regimen (methotrexate, cytarabine, thiotepa, and rituximab) significantly improved the prognosis of PCNSL patients, with an ORR of 87% and a CR rate.
Up to 49%, but there are still many patients who cannot achieve CR
.
In a real-world study in the United Kingdom, the toxic and side effects of the MATRIX induction program were more prominent.
After 156 PCNSL patients were treated with MATRIX, 10 patients (6%) were admitted to the ICU due to severe infection after the first cycle, and 44 patients (28%) of the patients had serious complications that did not require admission to the ICU, and 7 patients died (5 of them were infections)
.
Professor Huang said that for patients> 70 years old,> 65 years old with an ECOG performance score of 2 or more, or other organ comorbidities, it is not recommended to use the standard MATRix program
.
Overall, for patients with PCNSL, the CR rate of traditional induction chemotherapy is low, and the median time of maintenance of efficacy after chemotherapy with MTX regimen is less than 1 year
.
Therefore, Professor Huang suggested that patients younger than 65 years old should actively undergo autologous hematopoietic stem cell transplantation (ASCT).
A German multi-center phase 2 prospective study showed that newly diagnosed PCNSL patients undergoing ASCT after high-dose chemotherapy, the CR rate increased from 22% before transplantation to 77%
.
Professor Huang emphasized that ASCT is an important consolidation treatment method in PCNSL patients, and its efficacy is better than whole brain radiotherapy
.
How effective is the new drug in the treatment of PCNSL? In recent years, new drugs such as lenalidomide, BTK inhibitors, and PD-1 inhibitors have made rapid progress.
Professor Huang said that how to use these new drugs to increase the CR rate of PCNSL is a problem that needs to be explored
.
The efficacy of lenalidomide in the treatment of relapsed/refractory (R/R) PCNSL has been generally recognized, with an ORR of 67%
.
Next, Professor Huang mainly introduced the research and exploration of BTK inhibitor and PD-1 in PCNSL
.
A Japanese clinical study exploring Tirabrutinib (currently the only BTK inhibitor approved for R/R PCNSL in the world) for the treatment of PCNSL, enrolled 44 R/R PCNSL patients with a median treatment of the second line, and proceeded at the same time.
The gene mutation detection of MYD88, CD79B and CARD11 was performed.
The median follow-up was 9.
1 months.
The results showed that the median progression-free survival (PFS) of the 320mg group was 2.
1 months, and the median PFS of the 480mg group was 5.
8 months
.
In addition, the study found that the efficacy of Tirabrutinib has nothing to do with gene mutations, but with CSF drug concentration
.
The BTK inhibitor ibrutinib is also an effective drug for the treatment of central nervous system lymphoma, with a single-agent ORR of up to 50%-80%, and ibrutinib is effective for both MYD88 mutant and wild-type patients
.
However, the remission time of BTK inhibitors for PCNSL is shorter.
Professor Huang said that the combination of BTK inhibitors and immunochemotherapy can significantly improve the efficacy
.
In addition, studies on the treatment of PCNSL with PD-1 inhibitors have also shown good results.
After treatment with PD-1 inhibitors, R/R PCNSL has achieved a long-lasting effect of 13-17 months, but the onset time is relatively slow.
2-4 months
.
Therefore, Professor Huang said that new drugs for the treatment of PCNSL still need more research and exploration
.
What are the problems faced in the treatment of elderly PCNSL? Current research shows that for elderly PCNSL patients, chemotherapy is more effective than whole brain radiotherapy, and stronger chemotherapy can help improve the therapeutic effect of elderly PCNSL
.
In addition, ASCT is also feasible for the treatment of elderly PCNSL patients.
EBMT analyzed the ASCT of 52 PCNSL patients in 11 centers from 2003 to 2016.
Among them, 15 received first-line ASCT treatment, 37 received rescue ASCT treatment, and ASCT The PFS rate in the next 2 years was 62%, the 2-year overall survival (OS) rate was 70.
8%, the median PFS was 51.
1 months, and the median OS was 122.
3 months
.
However, in general, patients over 70 years of age with PCNSL have little benefit from treatment, and the median OS is only half a year.
There are still huge challenges in the treatment of elderly patients
.
Finally, Professor Huang introduced the real-world data of 167 PCNSL patients treated from 2003 to 2017 reported by the Second Affiliated Hospital of Zhejiang University School of Medicine.
The median age of the patients was 58 years (17-96 years), and patients >70 years old accounted for 14.
2%, 75 cases (67%) received HD-MTX, 25 cases (17%) received radiotherapy alone, 65 cases (43%) received chemotherapy + radiotherapy, no ASCT cases
.
After 25 months of follow-up, the median PFS was 17 months, and the median OS was 37 months
.
In this regard, Professor Huang said that there is still much room for improvement in the efficacy of PCNSL, and he looks forward to more research on PCNSL new drug exploration and ASCT to improve the prognosis of PCNSL patients
.
Professor Huang Wenrong, Doctor of Medicine, Chief Physician, Master Tutor, Director of Lymphoma and Plasma Cell Disease, Department of Hematology, PLA General Hospital, Deputy Chairman, Lymph, Hematology and Tumor Committee, Beijing Anti-Cancer Association, Deputy Chairman, Hematology Committee, Chinese Society of Geriatrics The subject of the Standing Committee of the Chinese Research Hospital Association’s Blood Precision Diagnosis and Treatment Committee, the honorable person has undertaken the National Natural Science Foundation, the military project, the capital health development scientific research project, etc.
, and won the second prize of the military science and technology progress.
The first author or corresponding author is in Oncogene, 21 clinical SCl papers have been published in international journals such as Bone marrow transplant, Cell Transplantation, Frontier Oncology, Transfusion, Annals of Hematology, Clinical transplant, Leukemia&lymphoma, and more than 50 stamps have been published in domestic journals.
"Read the original text" and we will make progress together
.
The conference was co-sponsored by the Chinese Society of Clinical Oncology (CSCO), CSCO Anti-Leukemia Alliance and CSCO Anti-Lymphoma Alliance, and co-organized by the Institute of Hematology and Oncology of Harbin First Hospital affiliated to Harbin Institute of Technology and Peking University Cancer Hospital
.
At the meeting, Professor Huang Wenrong from the Department of Hematology, the Fifth Medical Center of the PLA General Hospital gave a report on the topic of "Problems in the Treatment of Primary Central Nervous System Lymphoma (PCNSL)".
The editor organized the main content as follows for readers Reference
.
What is the appropriate induction chemotherapy for PCNSL patients? Professor Huang said that the complete remission (CR) rate of high-dose methotrexate (HD-MTX) treatment of PCNSL is relatively low, only 18%
.
Studies have explored the efficacy of ultra-high-dose MTX (8g/m2) combined with temozolomide in the treatment of PCNSL, and the CR rate is as high as 66%
.
So can the application of ultra-large doses of MTX alone improve the remission rate of PCNSL? The German multi-center prospective phase 2 study showed that the overall response rate (ORR) of the ultra-high-dose MTX treatment of PCNSL is higher, but the CR rate is only 26.
6%, and the high-dose MTX has more serious side effects
.
Therefore, some researchers have explored the application of HD-MTX combined with other programs in PCNSL.
The results of a prospective study in 24 centers in 6 European countries showed that HD-MTX combined with high-dose cytarabine significantly improved the remission rate of PCNSL (ORR is 70%, CR rate is 46%), but it also significantly increases side effects
.
Later, Professor Huang introduced that in the IELSG32 study, the MATRix induction regimen (methotrexate, cytarabine, thiotepa, and rituximab) significantly improved the prognosis of PCNSL patients, with an ORR of 87% and a CR rate.
Up to 49%, but there are still many patients who cannot achieve CR
.
In a real-world study in the United Kingdom, the toxic and side effects of the MATRIX induction program were more prominent.
After 156 PCNSL patients were treated with MATRIX, 10 patients (6%) were admitted to the ICU due to severe infection after the first cycle, and 44 patients (28%) of the patients had serious complications that did not require admission to the ICU, and 7 patients died (5 of them were infections)
.
Professor Huang said that for patients> 70 years old,> 65 years old with an ECOG performance score of 2 or more, or other organ comorbidities, it is not recommended to use the standard MATRix program
.
Overall, for patients with PCNSL, the CR rate of traditional induction chemotherapy is low, and the median time of maintenance of efficacy after chemotherapy with MTX regimen is less than 1 year
.
Therefore, Professor Huang suggested that patients younger than 65 years old should actively undergo autologous hematopoietic stem cell transplantation (ASCT).
A German multi-center phase 2 prospective study showed that newly diagnosed PCNSL patients undergoing ASCT after high-dose chemotherapy, the CR rate increased from 22% before transplantation to 77%
.
Professor Huang emphasized that ASCT is an important consolidation treatment method in PCNSL patients, and its efficacy is better than whole brain radiotherapy
.
How effective is the new drug in the treatment of PCNSL? In recent years, new drugs such as lenalidomide, BTK inhibitors, and PD-1 inhibitors have made rapid progress.
Professor Huang said that how to use these new drugs to increase the CR rate of PCNSL is a problem that needs to be explored
.
The efficacy of lenalidomide in the treatment of relapsed/refractory (R/R) PCNSL has been generally recognized, with an ORR of 67%
.
Next, Professor Huang mainly introduced the research and exploration of BTK inhibitor and PD-1 in PCNSL
.
A Japanese clinical study exploring Tirabrutinib (currently the only BTK inhibitor approved for R/R PCNSL in the world) for the treatment of PCNSL, enrolled 44 R/R PCNSL patients with a median treatment of the second line, and proceeded at the same time.
The gene mutation detection of MYD88, CD79B and CARD11 was performed.
The median follow-up was 9.
1 months.
The results showed that the median progression-free survival (PFS) of the 320mg group was 2.
1 months, and the median PFS of the 480mg group was 5.
8 months
.
In addition, the study found that the efficacy of Tirabrutinib has nothing to do with gene mutations, but with CSF drug concentration
.
The BTK inhibitor ibrutinib is also an effective drug for the treatment of central nervous system lymphoma, with a single-agent ORR of up to 50%-80%, and ibrutinib is effective for both MYD88 mutant and wild-type patients
.
However, the remission time of BTK inhibitors for PCNSL is shorter.
Professor Huang said that the combination of BTK inhibitors and immunochemotherapy can significantly improve the efficacy
.
In addition, studies on the treatment of PCNSL with PD-1 inhibitors have also shown good results.
After treatment with PD-1 inhibitors, R/R PCNSL has achieved a long-lasting effect of 13-17 months, but the onset time is relatively slow.
2-4 months
.
Therefore, Professor Huang said that new drugs for the treatment of PCNSL still need more research and exploration
.
What are the problems faced in the treatment of elderly PCNSL? Current research shows that for elderly PCNSL patients, chemotherapy is more effective than whole brain radiotherapy, and stronger chemotherapy can help improve the therapeutic effect of elderly PCNSL
.
In addition, ASCT is also feasible for the treatment of elderly PCNSL patients.
EBMT analyzed the ASCT of 52 PCNSL patients in 11 centers from 2003 to 2016.
Among them, 15 received first-line ASCT treatment, 37 received rescue ASCT treatment, and ASCT The PFS rate in the next 2 years was 62%, the 2-year overall survival (OS) rate was 70.
8%, the median PFS was 51.
1 months, and the median OS was 122.
3 months
.
However, in general, patients over 70 years of age with PCNSL have little benefit from treatment, and the median OS is only half a year.
There are still huge challenges in the treatment of elderly patients
.
Finally, Professor Huang introduced the real-world data of 167 PCNSL patients treated from 2003 to 2017 reported by the Second Affiliated Hospital of Zhejiang University School of Medicine.
The median age of the patients was 58 years (17-96 years), and patients >70 years old accounted for 14.
2%, 75 cases (67%) received HD-MTX, 25 cases (17%) received radiotherapy alone, 65 cases (43%) received chemotherapy + radiotherapy, no ASCT cases
.
After 25 months of follow-up, the median PFS was 17 months, and the median OS was 37 months
.
In this regard, Professor Huang said that there is still much room for improvement in the efficacy of PCNSL, and he looks forward to more research on PCNSL new drug exploration and ASCT to improve the prognosis of PCNSL patients
.
Professor Huang Wenrong, Doctor of Medicine, Chief Physician, Master Tutor, Director of Lymphoma and Plasma Cell Disease, Department of Hematology, PLA General Hospital, Deputy Chairman, Lymph, Hematology and Tumor Committee, Beijing Anti-Cancer Association, Deputy Chairman, Hematology Committee, Chinese Society of Geriatrics The subject of the Standing Committee of the Chinese Research Hospital Association’s Blood Precision Diagnosis and Treatment Committee, the honorable person has undertaken the National Natural Science Foundation, the military project, the capital health development scientific research project, etc.
, and won the second prize of the military science and technology progress.
The first author or corresponding author is in Oncogene, 21 clinical SCl papers have been published in international journals such as Bone marrow transplant, Cell Transplantation, Frontier Oncology, Transfusion, Annals of Hematology, Clinical transplant, Leukemia&lymphoma, and more than 50 stamps have been published in domestic journals.
"Read the original text" and we will make progress together
