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Marginal zone lymphoma (MZL) is a heterogeneous indolent disease
.
Extranodal MZL of mucosa-associated lymphoid tissue is the most common type, accounting for about 70% of all MZL, and may involve any anatomical site
.
Splenic MZL accounts for about 20% of all MZL, and lymph node MZL is the rarest type of MZL
.
Overall, the overall survival (OS) of MZL is good, but the disease relapses frequently, which may seriously affect the quality of life of patients
.
Therefore, patients with MZL may require multi-line therapy
.
The front-line treatment of MZL usually chooses treatments that can effectively local control the disease and have no side effects (or fewer side effects)
.
Front-line treatments mainly include radiotherapy, surgery or monoclonal antibody therapy
.
For patients who are late or relapsed at the time of treatment, if local treatment is ineffective, systemic treatment and chemotherapy can be selected
.
Targeted drugs and new drugs can provide patients with alternative treatment options without chemotherapy
.
This article briefly summarizes the new drugs currently used in patients with relapsed and refractory (R/R) MZL
.
Bruton's tyrosine kinase (BTK) inhibitor inhibits B cell signal transduction by blocking the BTK signaling pathway, which can hinder the migration, proliferation and survival of tumor components in B cell malignant tumors
.
Ibrutinib is a "first-in-class" covalent BTK inhibitor, active against all MZL subtypes
.
The use of the second-generation BTK inhibitor Zebutinib in R/R MZL is currently being explored
.
The results of a phase II clinical study of ibrutinib involving 63 patients with MZL confirmed the efficacy and safety of ibrutinib (560mg/day) in the treatment of R/R MZL
.
About 50% of the patients included in the study were extranodal MZL, 22% were splenic MZL, and 22% were lymph node MZL
.
Long-term follow-up data showed that the overall response rate (ORR) of ibrutinib treatment for R/R MZL was 58%, and the complete response (CR) rate was 10%
.
At a median follow-up of 33 months, the median duration of response (DOR) was 27.
6 months, the median progression-free survival (PFS) was 15.
7 months, and the median overall survival (OS) was not reached
.
The remission of all subtypes of MZL was consistent
.
Ibrutinib is currently approved by the U.
S.
Food and Drug Administration (FDA) for the treatment of MZL patients who have previously received at least one anti-CD20 monoclonal antibody treatment failure
.
Zebutinib Zebutinib can increase the BTK binding rate and reduce off-target toxicity
.
The phase II Magnolia study (BGB-3111-214) included 68 patients with R/R MZL who had previously received multi-line therapy and received 160 mg zebutinib twice daily
.
The median age of the patients included in the study was 70 years old, and one third of the patients did not respond to previous treatments
.
The results of the study showed that the ORR of Zebutinib for R/R MZL was 74%, the CR rate was 24%, and the CR rate of patients with extranodal MZL reached 40%
.
Time to remission is 2.
8 months, similar to ibrutinib
.
The 6-month PFS rate was 80%, and the 9-month PFS rate was 67%
.
Phosphatidylinositol 3-kinase (PI3K) inhibitor PI3K inhibitors also have therapeutic prospects in R/R MZL
.
Related studies have explored the efficacy of PI3K inhibitors Idelalisib, Duvelisib, Copanlisib, Parsaclisib and Umbralisib in patients with R/R indolent lymphoma (including R/R MZL patients)
.
The results of the study show that the ORR of PI3K inhibitors in R/R MZL patients is 47%-78%, but the CR rate is low, only 7%-33%.
At the same time, the treatment of PI3K inhibitors is accompanied by infection and inflammation adverse events.
Or metabolic changes and other related toxicity
.
Among PI3K inhibitors, Copanlisib and Umbralisib have relatively better efficacy data in R/R MZL
.
The Copanlisib CHRONOS-1 study evaluated the efficacy and safety of Copanlisib as a monotherapy for R/R MZL
.
The study enrolled 23 patients with R/R MZL, of which 50% were refractory to the last treatment, and 83% were refractory to all previous treatments
.
The results of the study showed that the ORR of Copanlisib treatment of R/R MZL patients was 78%, and the CR rate was 13%
.
The median DOR was 17 months, and 45% of patients maintained remission after 2 years of treatment
.
The median PFS was 24 months, and the 2-year PFS rate was 56%
.
The CHRONOS-3 study subsequently explored the efficacy of the Copanlisib combination regimen in R/R MZL patients.
The study included R/R MZL patients who were randomly assigned to receive Copanlisib plus rituximab (66 cases) or placebo plus rituximab Anti-(29 cases) treatment
.
The results of the study showed that the ORR of patients in the Copanlisib combined with rituximab group was 76%, and the CR rate was 39%, while the ORR and CR rates of the rituximab combined with placebo group were 41% and 10%, respectively
.
The median PFS of the experimental group was 22 months, and the median PFS of the control group was 12 months
.
The study confirmed the activity of Copanlisib in R/R MZL patients and confirmed that it is effective in combination therapy with rituximab
.
The most common adverse events (AE) in patients receiving Copanlisib in the study were hyperglycemia and hypertension
.
Umbralisib Umbralisib is a dual-effect inhibitor of PI3Kδ and CK1-ε
.
The Phase II UNITY-NHL study explored the efficacy of Umbralisib in MZL patients who have previously received multiple lines of therapy
.
The study included 69 R/R MZL patients (55 extranodal MZL, 29 lymph node MZL, and 16 splenic MZL), of which 25% were refractory to the last treatment
.
The results of the study showed that the median time to remission for R/R MZL patients was 2.
8 months, the ORR was 49%, and the CR rate was 16%
.
The treatment remission of the three MZL subtypes was consistent
.
At a median follow-up of 28 months, neither the median DOR nor the median PFS was achieved
.
It is concluded that the key to the success of R/R MZL treatment is the sequential application of new treatment strategies
.
Targeted drugs and new drugs provide new treatment opportunities for MZL patients who have previously received multiple lines of treatment, while avoiding repeated use of cytotoxic drugs
.
Reference source: 1.
Alessandro Broccoli.
2021 SOHO.
EXABS-137-NHL.
Stamp "read the original text", we make progress together
.
Extranodal MZL of mucosa-associated lymphoid tissue is the most common type, accounting for about 70% of all MZL, and may involve any anatomical site
.
Splenic MZL accounts for about 20% of all MZL, and lymph node MZL is the rarest type of MZL
.
Overall, the overall survival (OS) of MZL is good, but the disease relapses frequently, which may seriously affect the quality of life of patients
.
Therefore, patients with MZL may require multi-line therapy
.
The front-line treatment of MZL usually chooses treatments that can effectively local control the disease and have no side effects (or fewer side effects)
.
Front-line treatments mainly include radiotherapy, surgery or monoclonal antibody therapy
.
For patients who are late or relapsed at the time of treatment, if local treatment is ineffective, systemic treatment and chemotherapy can be selected
.
Targeted drugs and new drugs can provide patients with alternative treatment options without chemotherapy
.
This article briefly summarizes the new drugs currently used in patients with relapsed and refractory (R/R) MZL
.
Bruton's tyrosine kinase (BTK) inhibitor inhibits B cell signal transduction by blocking the BTK signaling pathway, which can hinder the migration, proliferation and survival of tumor components in B cell malignant tumors
.
Ibrutinib is a "first-in-class" covalent BTK inhibitor, active against all MZL subtypes
.
The use of the second-generation BTK inhibitor Zebutinib in R/R MZL is currently being explored
.
The results of a phase II clinical study of ibrutinib involving 63 patients with MZL confirmed the efficacy and safety of ibrutinib (560mg/day) in the treatment of R/R MZL
.
About 50% of the patients included in the study were extranodal MZL, 22% were splenic MZL, and 22% were lymph node MZL
.
Long-term follow-up data showed that the overall response rate (ORR) of ibrutinib treatment for R/R MZL was 58%, and the complete response (CR) rate was 10%
.
At a median follow-up of 33 months, the median duration of response (DOR) was 27.
6 months, the median progression-free survival (PFS) was 15.
7 months, and the median overall survival (OS) was not reached
.
The remission of all subtypes of MZL was consistent
.
Ibrutinib is currently approved by the U.
S.
Food and Drug Administration (FDA) for the treatment of MZL patients who have previously received at least one anti-CD20 monoclonal antibody treatment failure
.
Zebutinib Zebutinib can increase the BTK binding rate and reduce off-target toxicity
.
The phase II Magnolia study (BGB-3111-214) included 68 patients with R/R MZL who had previously received multi-line therapy and received 160 mg zebutinib twice daily
.
The median age of the patients included in the study was 70 years old, and one third of the patients did not respond to previous treatments
.
The results of the study showed that the ORR of Zebutinib for R/R MZL was 74%, the CR rate was 24%, and the CR rate of patients with extranodal MZL reached 40%
.
Time to remission is 2.
8 months, similar to ibrutinib
.
The 6-month PFS rate was 80%, and the 9-month PFS rate was 67%
.
Phosphatidylinositol 3-kinase (PI3K) inhibitor PI3K inhibitors also have therapeutic prospects in R/R MZL
.
Related studies have explored the efficacy of PI3K inhibitors Idelalisib, Duvelisib, Copanlisib, Parsaclisib and Umbralisib in patients with R/R indolent lymphoma (including R/R MZL patients)
.
The results of the study show that the ORR of PI3K inhibitors in R/R MZL patients is 47%-78%, but the CR rate is low, only 7%-33%.
At the same time, the treatment of PI3K inhibitors is accompanied by infection and inflammation adverse events.
Or metabolic changes and other related toxicity
.
Among PI3K inhibitors, Copanlisib and Umbralisib have relatively better efficacy data in R/R MZL
.
The Copanlisib CHRONOS-1 study evaluated the efficacy and safety of Copanlisib as a monotherapy for R/R MZL
.
The study enrolled 23 patients with R/R MZL, of which 50% were refractory to the last treatment, and 83% were refractory to all previous treatments
.
The results of the study showed that the ORR of Copanlisib treatment of R/R MZL patients was 78%, and the CR rate was 13%
.
The median DOR was 17 months, and 45% of patients maintained remission after 2 years of treatment
.
The median PFS was 24 months, and the 2-year PFS rate was 56%
.
The CHRONOS-3 study subsequently explored the efficacy of the Copanlisib combination regimen in R/R MZL patients.
The study included R/R MZL patients who were randomly assigned to receive Copanlisib plus rituximab (66 cases) or placebo plus rituximab Anti-(29 cases) treatment
.
The results of the study showed that the ORR of patients in the Copanlisib combined with rituximab group was 76%, and the CR rate was 39%, while the ORR and CR rates of the rituximab combined with placebo group were 41% and 10%, respectively
.
The median PFS of the experimental group was 22 months, and the median PFS of the control group was 12 months
.
The study confirmed the activity of Copanlisib in R/R MZL patients and confirmed that it is effective in combination therapy with rituximab
.
The most common adverse events (AE) in patients receiving Copanlisib in the study were hyperglycemia and hypertension
.
Umbralisib Umbralisib is a dual-effect inhibitor of PI3Kδ and CK1-ε
.
The Phase II UNITY-NHL study explored the efficacy of Umbralisib in MZL patients who have previously received multiple lines of therapy
.
The study included 69 R/R MZL patients (55 extranodal MZL, 29 lymph node MZL, and 16 splenic MZL), of which 25% were refractory to the last treatment
.
The results of the study showed that the median time to remission for R/R MZL patients was 2.
8 months, the ORR was 49%, and the CR rate was 16%
.
The treatment remission of the three MZL subtypes was consistent
.
At a median follow-up of 28 months, neither the median DOR nor the median PFS was achieved
.
It is concluded that the key to the success of R/R MZL treatment is the sequential application of new treatment strategies
.
Targeted drugs and new drugs provide new treatment opportunities for MZL patients who have previously received multiple lines of treatment, while avoiding repeated use of cytotoxic drugs
.
Reference source: 1.
Alessandro Broccoli.
2021 SOHO.
EXABS-137-NHL.
Stamp "read the original text", we make progress together
