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This article is from the NEJM Journal Watch.
A Third-Generation Bruton Tyrosine Kinase Inhibitor Review Author: Michael E.
Williams, MD, ScMpirtobrutinib Patients with B-cell malignancies resistant to acid kinase inhibitors (BTKi) achieved lasting remission
.
The FDA-approved covalent and irreversible combination of BTKi (ibrutinib, acalabrutinib, and zanubrutinib) is a component of the treatment plan for B-cell malignancies, but tumor cell resistance and patient intolerance are common
.
The researchers published the results of an industry-sponsored, multi-center Phase 1/2 trial of the new reversibly conjugated BTKi pirtobrutinib (LOXO-305), which included 323 cases of relapsed or refractory chronic lymphocytic leukemia/small lymphoid Patients with cell lymphoma (CLL/SLL), mantle cell lymphoma (MCL), Waldenström macroglobulinemia (WM), follicular lymphoma (FL) or diffuse large B-cell lymphoma (DLBCL)
.
Patients who had previously received BTKi treatment were also included in the trial
.
In the 203 patients in the phase 1 dose exploration cohort, the investigator found no dose-limiting toxicity; 200 mg orally once daily is recommended as the phase 2 dose
.
The overall response rate (ORR) of 269 patients with curative effect can be evaluated is as follows (Table 1)
.
Table 1.
Total remission rate after pirtobrutinib treatment.
The researchers observed that patients who had received a large number of treatments in the past achieved remission, including patients who had received stem cell transplantation or CAR T cell therapy
.
75% of patients with BTK C481 mutation (mediating resistance to irreversible BTKi) and 79% of patients with 17p deletion or TP53 mutation achieved CLL remission
.
During the limited follow-up period (median 4 to 6 months), the remission of most patients continued
.
Toxicity grade 3 or higher includes: neutropenia (10%) and anemia (4%); grade 1 to 2 toxicities include bruising (16%), bleeding (5%) and atrial fibrillation (1%) )
.
Infections are not common and are mainly upper respiratory tract infections
.
Comment on pirtobrutinib to achieve remission of a series of B-cell malignancies, including patients who are resistant or intolerant to other BTKi, which suggests that the reversible combination makes the drug have benefits that other drugs do not have
.
The drug is generally well tolerated, but the follow-up time needs to be extended to further evaluate the toxicity
.
Although the number of FL and DLBCL patients is small, compared with the existing BTKi, this study shows the potential of the above-mentioned lymphoma patients to benefit from treatment.
This topic needs further discussion
.
The reviewed article Mato AR et al.
Pirtobrutinib in relapsed or refractory B-cell malignancies (BRUIN): A phase 1/2 study.
Lancet 2021 Mar 6; 397:892.
(https://doi.
org/10.
1016/S0140- 6736(21)00224-5)Michot JM and Ribrag V.
Pirtobrutinib shows evidence to inaugurate a third generation of BTK inhibitors.
Lancet 2021 Mar 6; 397:855.
(https://doi.
org/10.
1016/S0140-6736( 21)00235-X) Related reading NEJM Journal Watch The NEJM Journal Watch is published by NEJM Group.
Internationally renowned doctors are invited to comment on important papers in the medical field to help doctors understand and use the latest developments
.
"NEJM Frontiers of Medicine" is translated several times a week, published on the app and official website, and selected 2-3 articles are published on WeChat
.
Copyright information This article was translated, written or commissioned by the "NEJM Frontiers of Medicine" jointly created by the Jiahui Medical Research and Education Group (J-Med) and the "New England Journal of Medicine" (NEJM)
.
The Chinese translation of the full text and the included diagrams are exclusively authorized by the NEJM Group
.
If you need to reprint, please leave a message or contact nejmqianyan@nejmqianyan.
cn
.
Unauthorized translation is an infringement, and the copyright owner reserves the right to pursue legal liabilities
.
A Third-Generation Bruton Tyrosine Kinase Inhibitor Review Author: Michael E.
Williams, MD, ScMpirtobrutinib Patients with B-cell malignancies resistant to acid kinase inhibitors (BTKi) achieved lasting remission
.
The FDA-approved covalent and irreversible combination of BTKi (ibrutinib, acalabrutinib, and zanubrutinib) is a component of the treatment plan for B-cell malignancies, but tumor cell resistance and patient intolerance are common
.
The researchers published the results of an industry-sponsored, multi-center Phase 1/2 trial of the new reversibly conjugated BTKi pirtobrutinib (LOXO-305), which included 323 cases of relapsed or refractory chronic lymphocytic leukemia/small lymphoid Patients with cell lymphoma (CLL/SLL), mantle cell lymphoma (MCL), Waldenström macroglobulinemia (WM), follicular lymphoma (FL) or diffuse large B-cell lymphoma (DLBCL)
.
Patients who had previously received BTKi treatment were also included in the trial
.
In the 203 patients in the phase 1 dose exploration cohort, the investigator found no dose-limiting toxicity; 200 mg orally once daily is recommended as the phase 2 dose
.
The overall response rate (ORR) of 269 patients with curative effect can be evaluated is as follows (Table 1)
.
Table 1.
Total remission rate after pirtobrutinib treatment.
The researchers observed that patients who had received a large number of treatments in the past achieved remission, including patients who had received stem cell transplantation or CAR T cell therapy
.
75% of patients with BTK C481 mutation (mediating resistance to irreversible BTKi) and 79% of patients with 17p deletion or TP53 mutation achieved CLL remission
.
During the limited follow-up period (median 4 to 6 months), the remission of most patients continued
.
Toxicity grade 3 or higher includes: neutropenia (10%) and anemia (4%); grade 1 to 2 toxicities include bruising (16%), bleeding (5%) and atrial fibrillation (1%) )
.
Infections are not common and are mainly upper respiratory tract infections
.
Comment on pirtobrutinib to achieve remission of a series of B-cell malignancies, including patients who are resistant or intolerant to other BTKi, which suggests that the reversible combination makes the drug have benefits that other drugs do not have
.
The drug is generally well tolerated, but the follow-up time needs to be extended to further evaluate the toxicity
.
Although the number of FL and DLBCL patients is small, compared with the existing BTKi, this study shows the potential of the above-mentioned lymphoma patients to benefit from treatment.
This topic needs further discussion
.
The reviewed article Mato AR et al.
Pirtobrutinib in relapsed or refractory B-cell malignancies (BRUIN): A phase 1/2 study.
Lancet 2021 Mar 6; 397:892.
(https://doi.
org/10.
1016/S0140- 6736(21)00224-5)Michot JM and Ribrag V.
Pirtobrutinib shows evidence to inaugurate a third generation of BTK inhibitors.
Lancet 2021 Mar 6; 397:855.
(https://doi.
org/10.
1016/S0140-6736( 21)00235-X) Related reading NEJM Journal Watch The NEJM Journal Watch is published by NEJM Group.
Internationally renowned doctors are invited to comment on important papers in the medical field to help doctors understand and use the latest developments
.
"NEJM Frontiers of Medicine" is translated several times a week, published on the app and official website, and selected 2-3 articles are published on WeChat
.
Copyright information This article was translated, written or commissioned by the "NEJM Frontiers of Medicine" jointly created by the Jiahui Medical Research and Education Group (J-Med) and the "New England Journal of Medicine" (NEJM)
.
The Chinese translation of the full text and the included diagrams are exclusively authorized by the NEJM Group
.
If you need to reprint, please leave a message or contact nejmqianyan@nejmqianyan.
cn
.
Unauthorized translation is an infringement, and the copyright owner reserves the right to pursue legal liabilities
.
