Jaypirca (pirtobrutinib)
Research Synopsis
- - Jaypirca, the brand name for pirtobrutinib, is a non-covalent Bruton's tyrosine kinase (BTK) inhibitor recently developed to address challenges associated with prior BTK therapies.
- - Clinical trials, particularly the BRUIN study, have demonstrated promising results, showing pirtobrutinib effectively treats relapsed or refractory B-cell malignancies, achieving a notable 62% overall response rate among patients with chronic lymphocytic leukemia (CLL) who had previously undergone other BTK treatments.
- - Pirtobrutinib is noted for its manageable side effects, with common adverse events reported being fatigue and diarrhea, and it has established a safe recommended dosage of 200 mg daily without dose-limiting toxicities.
- - Research highlighted the drug's ability to inhibit BTK activation and downstream signaling in CLL cell lines, proving effective against both the wild-type and mutant versions of the BTK protein.
- - The emergence of pirtobrutinib as a third-generation BTK inhibitor offers potential solutions for patients who are resistant to traditional covalent BTK inhibitors, which are linked to significant side effects and resistance mechanisms.
- - Studies have identified genetic mutations in patients, particularly at the BTK binding site, that contribute to treatment resistance, emphasizing the need for continuous research to understand the full spectrum of resistance mechanisms in CLL.
- - Pirtobrutinib is positioned to play a significant role in expanding treatment options for diverse B-cell malignancies, including mantle cell lymphoma, with ongoing phase III studies comparing its efficacy with standard therapies.
- - The drug’s novel mechanism avoids binding to the C481 residue, a common site where resistance typically develops, reinforcing its potential as a go-to therapy in complex cases of B-cell malignancies.
- - Overall, current research indicates that pirtobrutinib is a key addition to the arsenal against B-cell cancers, promising improved outcomes for patients who have exhausted other treatment avenues.
- - The drug's success marks a step forward in the field of targeted cancer therapies, particularly for elderly or unfit patients who may not tolerate standard aggressive treatments well.
Jaypirca (pirtobrutinib)
Pirtobrutinib shows evidence to inaugurate a third generation of BTK inhibitors.
London, UK
2 hours ago
1 Received
$100 - $150
Hourly Rate
Pirtobrutinib in relapsed or refractory B-cell malignancies (BRUIN): a phase 1/2 study.
London, UK
2 hours ago
1 Received
- Covalent BTK inhibitors are effective for B-cell malignancies, but patients often stop using them due to resistance or side effects, prompting the evaluation of pirtobrutinib, a new reversible BTK inhibitor.
- In a phase 1/2 trial with 323 patients, pirtobrutinib showed no dose-limiting toxicities and the recommended dose was established at 200 mg daily, with some reported side effects like fatigue and diarrhea.
- Among patients with chronic lymphocytic leukemia or small lymphocytic lymphoma who previously used other BTK inhibitors, pirtobrutinib demonstrated a 62% overall response rate, indicating significant efficacy even in those who previously experienced treatment resistance or intolerance.*
$100 - $150
Hourly Rate
Initial pirtobrutinib data show promise.
London, UK
2 hours ago
1 Received
$100 - $150
Hourly Rate
BTK Inhibitor May Treat Drug-Resistant CLL, SLL.
London, UK
2 hours ago
1 Received
- - A reversible BTK inhibitor called pirtobrutinib shows promise for patients with B-cell cancers that haven't improved with other targeted treatments or can't handle the side effects of permanent BTK inhibitors.
- - In a phase I/II trial, patients who had previously used other BTK inhibitors experienced a 62% overall response rate to pirtobrutinib.
- - This treatment offers a new option for patients facing challenges with existing therapies in their battle against B-cell malignancies.
$100 - $150
Hourly Rate
How to Sequence Therapies in Waldenström Macroglobulinemia.
London, UK
2 hours ago
1 Received
- - There are various treatment options for Waldenström macroglobulinemia (WM), such as chemotherapy, monoclonal antibodies, proteasome inhibitors, and BTK inhibitors, and the best choice depends on the patient's condition and preferences.
- - Ibrutinib is generally preferred for patients with MYD88 mutations and no CXCR4 mutations, while other treatments are recommended for those with different genetic mutations; new combinations are being studied.
- - Autologous stem cell transplants may be an option for some patients in relapse, and participation in clinical trials is encouraged to explore promising agents like venetoclax and new BTK inhibitors.
$100 - $150
Hourly Rate
The Role of BTK Inhibition in the Treatment of Chronic Lymphocytic Leukemia: A Clinical View.
London, UK
2 hours ago
1 Received
- The B cell receptor (BCR) signaling pathway is crucial for B cell survival and plays a significant role in B cell cancers like chronic lymphocytic leukemia (CLL).
- Ibrutinib, a first-generation tyrosine kinase inhibitor, effectively disrupts Bruton's tyrosine kinase (BTK) activity, leading to CLL cell death and prolonged disease control, though most patients still require ongoing treatment.
- Advances in drug design aim to reduce side effects and combat resistance through the development of more selective inhibitors and strategies to degrade BTK protein, marking a shift to chemotherapy-free treatments that significantly improve survival rates for CLL patients.
$100 - $150
Hourly Rate
Treatment Options for Elderly/Unfit Patients with Chronic Lymphocytic Leukemia in the Era of Targeted Drugs: A Comprehensive Review.
London, UK
2 hours ago
1 Received
- Chronic lymphocytic leukemia (CLL) incidence rises significantly with age, particularly in patients over 85, emphasizing the need for personalized treatment strategies.
- Current research suggests that traditional chemoimmunotherapy is mainly suited for elderly patients who are fit and have minimal health issues, while newer therapies like BCR inhibitors are recommended for both fit and unfit patients, especially those with high-risk genetic traits.
- The introduction of second-generation inhibitors presents safer treatment options, allowing healthcare providers to make informed decisions that prioritize both the effectiveness of the treatment and the overall health and quality of life of older patients with CLL.
$100 - $150
Hourly Rate
The TKI Era in Chronic Leukemias.
London, UK
2 hours ago
1 Received
- * The introduction of targeted therapies, such as multiple generations of BCR-ABL1 inhibitors (like imatinib and ponatinib) and BTK inhibitors (like ibrutinib), has revolutionized treatment for CML and CLL, significantly improving patient outcomes and potentially allowing some patients to discontinue therapy.
- * While PI3K inhibitors are effective in CLL, they are used less frequently due to side effects
$100 - $150
Hourly Rate
Bruton Tyrosine Kinase Inhibitors in B-Cell Malignancies: Their Use and Differential Features.
London, UK
2 hours ago
1 Received
- The introduction of BTK inhibitors, starting with ibrutinib, has significantly improved treatment outcomes for B-cell malignancies.
- Second-generation BTK inhibitors, like acalabrutinib and zanubrutinib, were created to minimize side effects compared to the first-generation agents.
- Third-generation non-covalent BTK inhibitors, such as pirtobrutinib, are now in advanced clinical trials, showcasing effectiveness across various B-cell cancers while offering manageable side effects.
$100 - $150
Hourly Rate
Mechanisms of Resistance to Noncovalent Bruton's Tyrosine Kinase Inhibitors.
London, UK
2 hours ago
1 Received
- Covalent Bruton's tyrosine kinase (BTK) inhibitors have significantly improved treatment for B-cell cancers, such as chronic lymphocytic leukemia (CLL), but patients can develop resistance due to mutations at the BTK binding site and other mechanisms.
- This study analyzed genomic data from CLL patients treated with the noncovalent BTK inhibitor pirtobrutinib and identified several mutations in BTK and phospholipase C gamma 2 (PLCγ2) that contribute to resistance.
- The findings highlight new mechanisms of resistance that allow CLL to escape treatment effects, affecting both noncovalent and certain covalent BTK inhibitors, indicating a need for further research in overcoming these challenges.
$100 - $150
Hourly Rate
The Role of Bruton's Kinase Inhibitors in Chronic Lymphocytic Leukemia: Current Status and Future Directions.
London, UK
2 hours ago
1 Received
- The introduction of Bruton's tyrosine kinase (BTK) inhibitors has significantly improved the treatment and clinical outcomes for patients with chronic lymphocytic leukemia (CLL).
- BTK inhibitors are divided into irreversible (like ibrutinib, approved in 2013) and reversible types, with newer agents focusing on minimizing side effects associated with the original drug.
- This review discusses the pharmacology, effectiveness, safety, dosing protocols, and potential drug interactions of BTK inhibitors in CLL therapy, as well as their future implications in treatment.
$100 - $150
Hourly Rate
The emerging role of pirtobrutinib in chronic lymphocytic leukemia.
London, UK
2 hours ago
1 Received
$100 - $150
Hourly Rate
New Directions for Mantle Cell Lymphoma in 2022.
London, UK
2 hours ago
1 Received
- - Mantle cell lymphoma is a rare type of B-cell non-Hodgkin lymphoma that varies significantly in its clinical and biological characteristics, making risk stratification at diagnosis essential for patient outcomes.
- - The Mantle Cell Lymphoma International Prognostic Index-Combined, which includes factors like the Ki67 index, is an important tool for prognosis, while mutations are linked to poorer responses to treatments, especially intensive chemoimmunotherapy.
- - New targeted therapies, including Bruton tyrosine kinase inhibitors and CAR T-cell therapies, are emerging as effective options for patients, and research is shifting towards personalized treatment approaches based on individual risk factors and biological markers.
$100 - $150
Hourly Rate
Pirtobrutinib inhibits wild-type and mutant Bruton's tyrosine kinase-mediated signaling in chronic lymphocytic leukemia.
London, UK
2 hours ago
1 Received
- Pirtobrutinib (LOXO-305) is a reversible inhibitor of Bruton's tyrosine kinase (BTK), developed to target CLL cases resistant to ibrutinib due to mutations in the C481 kinase domain.
- The drug showed effectiveness in different experimental systems, significantly inhibiting BTK activation and downstream signaling in CLL cell lines and primary CLL cells, with some positive effects observed in mouse models.
- Initial treatment with pirtobrutinib showed inhibition of biomarkers CCL3 and CCL4 and other BCR pathway alterations, but the effects weakened in cases with additional mutations, highlighting the need for further long-term studies on its efficacy and potential resistance mechanisms.
$100 - $150
Hourly Rate
New Treatment Options for Newly-Diagnosed and Relapsed Chronic Lymphocytic Leukemia.
London, UK
2 hours ago
1 Received
- Advances in understanding chronic lymphocytic leukemia (CLL) biology have led to new treatments, improving patient outcomes despite the disease remaining incurable.
- Key treatments include Bruton's tyrosine kinase (BTK) inhibitors, PI3K inhibitors, venetoclax, and CD20 monoclonal antibodies for both initial and relapsed cases, with ibrutinib being the first approved BTK inhibitor.
- Newer therapies like reversible BTK inhibitors and phosphatidylinositol 3-kinase (PI3K) inhibitors show promise, while cellular therapies are becoming options for patients who do not respond to existing treatments.
$100 - $150
Hourly Rate
The potential of pirtobrutinib in multiple B-cell malignancies.
London, UK
2 hours ago
1 Received
- Bruton’s tyrosine kinase (BTK) is a key player in B-cell signaling and is targeted by FDA-approved covalent inhibitors like ibrutinib and acalabrutinib, which improve survival in B-cell cancers but have limitations such as side effects and disease progression.
- Pirtobrutinib is a new type of BTK inhibitor that works non-covalently, meaning it binds to BTK without affecting the C481 amino acid, and has shown promising results in a recent clinical trial for patients with relapsed/refractory B-cell malignancies.
- This review discusses the importance of non-covalent BTK inhibitors like pirtobrutinib,
$100 - $150
Hourly Rate
Integrin Signaling Shaping BTK-Inhibitor Resistance.
London, UK
2 hours ago
1 Received
- Integrins, particularly beta1 integrins like VLA-4, play a crucial role in tumor cell adhesion and can contribute to drug resistance in cancer, particularly in chronic lymphocytic leukemia (CLL).
- VLA-4 activation involves a complex signaling process that may open up new therapeutic targets, especially since current treatment strategies are shifting towards targeting BCR signaling.
- While BTK inhibitors like ibrutinib have shown effectiveness in treating CLL, they come with challenges such as the need for continuous use, potential resistance, and side effects, highlighting the need for alternative therapies to overcome these issues.
$100 - $150
Hourly Rate
SOHO State of the Art Updates and Next Questions: Targeted therapies and emerging novel treatment approaches for Waldenström Macroglobulinemia.
London, UK
2 hours ago
1 Received
- Waldenström Macroglobulinemia (WM) is a rare blood cancer involving abnormal lymphoplasmacytic cells in the bone marrow, leading to the production of excess IgM.
- About 90-95% of WM patients have mutations in genes MYD88 and CXCR4, influencing treatment options.
- Current treatments often include rituximab with various chemotherapy agents and newer targeted therapies like BTK inhibitors, with ongoing research into combination therapies to improve effectiveness and reduce side effects.
$100 - $150
Hourly Rate
Enrichment of BTK Leu528Trp mutations in patients with CLL on zanubrutinib: potential for pirtobrutinib cross-resistance.
London, UK
2 hours ago
1 Received
- The study examines the effectiveness of covalent Bruton's tyrosine kinase inhibitors (BTKis) in chronic lymphocytic leukemia (CLL), focusing on how resistance develops, particularly with mutations in the BTK gene.
- A significant mutation, BTK Leu528Trp, was found more frequently in patients treated with the newer drug zanubrutinib compared to older drug ibrutinib, indicating a potential resistance mechanism.
- Patients with the BTK Leu528Trp mutation showed cross-resistance when treated with the noncovalent BTKi pirtobrutinib, but they improved with venetoclax-based treatment, suggesting important implications for future treatment sequencing in CLL.
$100 - $150
Hourly Rate
BRUIN MCL-321: phase III study of pirtobrutinib versus investigator choice of BTK inhibitor in BTK inhibitor naive mantle cell lymphoma.
London, UK
2 hours ago
1 Received
- Treatment with covalent Bruton tyrosine kinase inhibitors (BTKi) is important for managing relapsed mantle cell lymphoma, but these treatments aren't curative and many patients still relapse.
- Pirtobrutinib is a new, noncovalent BTKi that effectively targets both normal and mutant forms of BTK and offers continuous inhibition due to its favorable oral pharmacology.
- A phase III study is underway to compare the effectiveness of pirtobrutinib against standard covalent BTKi treatments in patients with previously untreated mantle cell lymphoma.
$100 - $150
Hourly Rate