Publications by authors named "Jurczak W"
JCO SEQUOIA (ClinicalTrials.gov identifier: NCT03336333) is a phase III, randomized, open-label trial that compared the oral Bruton tyrosine kinase inhibitor zanubrutinib to bendamustine plus rituximab (BR) in treatment-naïve patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). The initial prespecified analysis (median follow-up, 26.
View Article and Find Full Text PDFClinical bleeding events are reported here from 773 patients with B-cell malignancies receiving pirtobrutinib monotherapy from the phase 1/2 BRUIN study (ClinicalTrials.gov identifier: NCT03740529), either in the presence or absence of antithrombotic therapy (antithrombotic exposed [AT-E], = 216; antithrombotic nonexposed [AT-NE], = 557). Among the AT-E cohort, 51.
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- Bruton tyrosine kinase inhibitors (BTKi) have significantly improved treatment for B-cell malignancies, but many patients stop using them due to side effects, with cardiac issues being the most common reason for discontinuation.* -
- The BRUIN study tested pirtobrutinib, a new non-covalent BTKi, on 127 patients who were intolerant to previous BTKi treatments, finding that many experienced fewer or no cardiac issues while showing a high overall response rate.* -
- Results indicated pirtobrutinib had a median time on treatment of 15.3 months, with notable side effects like fatigue and neutropenia; overall, it proved to be a safe and effective alternative for
Article Synopsis
- Epcoritamab, a bispecific antibody targeting CD3 and CD20, showed promising long-term results as a monotherapy for relapsed or refractory large B-cell lymphoma (LBCL) in the EPCORE NHL-1 study, with a 63.1% overall response rate and a 40.1% complete response rate after a median follow-up of 25.1 months.
- The estimated 24-month progression-free survival (PFS) and overall survival (OS) rates were 27.8% and 44.6%, respectively, with 64.2% of complete responders maintaining their response at that time.
- Most treatment-emergent adverse events were manageable, with cytokine release syndrome
The ALPINE trial established the superiority of zanubrutinib over ibrutinib in patients with relapsed/refractory chronic lymphocytic leukemia and small lymphocytic lymphoma; here, we present data from the final comparative analysis with extended follow-up. Overall, 652 patients received zanubrutinib (n = 327) or ibrutinib (n = 325). At an overall median follow-up of 42.
View Article and Find Full Text PDFThis multicenter, open-label, phase 1b study (ACE-LY-106) assessed the safety and efficacy of acalabrutinib, bendamustine, and rituximab (ABR) in treatment-naive (TN) and relapsed or refractory (R/R) mantle cell lymphoma (MCL). Patients received acalabrutinib from cycle 1 until disease progression or treatment discontinuation, bendamustine on days 1 and 2 of each cycle for up to 6 cycles, and rituximab on day 1 of each cycle for 6 cycles, continuing every other cycle from cycle 8 for 12 additional doses (TN cohort). Eighteen patients enrolled in the TN and 20 in the R/R cohort.
View Article and Find Full Text PDFIn this global phase 2 study in patients with relapsed/refractory follicular lymphoma (FL), zandelisib was administered on intermittent dosing to mitigate immune-related adverse events and infections that have been reported with oral PI3Kδ inhibitors administered daily continuously. Eligible patients with measurable disease and progression after at least two prior therapies were administered zandelisib until disease progression or intolerability. The primary efficacy endpoint was objective response rate (ORR) and the key secondary efficacy endpoint was duration of response (DOR).
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- Richter transformation is a serious form of aggressive lymphoma found in about 10% of chronic lymphocytic leukemia patients, with no approved treatments and a grim outlook.
- Pirtobrutinib, showing good results for patients with B-cell malignancies who have relapsed or are resistant to conventional therapies, is being studied for its safety and effectiveness in treating Richter transformation.
- The study included 82 adult patients who received pirtobrutinib daily, tracking overall response rates and safety, with results indicating the drug was well tolerated and active in this difficult subset of cancer patients.
Article Synopsis
- This study aimed to assess the effectiveness of epcoritamab, a new bispecific antibody, for treating patients with advanced follicular lymphoma who have already undergone multiple previous therapies.
- The research was part of the EPCORE NHL-1 trial, which took place at 88 sites across 15 countries and involved patients aged 18 and older with specific eligibility criteria, including having received at least two prior treatments.
- Treatment involved subcutaneous injections of epcoritamab in cycles, with a tailored dosing strategy to minimize the risk of cytokine release syndrome, and the primary focus was on evaluating the overall response rate and safety measures related to cytokine release.
Article Synopsis
- Pirtobrutinib is a new reversible drug that targets Bruton tyrosine kinase, showing effective results in treating B-cell malignancies with low patient dropout and dose reduction rates.
- A study from the BRUIN trial evaluated the safety of pirtobrutinib in patients who were treated for 12 months or more, revealing common side effects like fatigue and diarrhea, with most adverse events occurring in the first year of treatment.
- Overall, the findings suggest that pirtobrutinib has a favorable safety profile for long-term use, with no new significant toxicity concerns reported.
This phase 1b study evaluated safety and efficacy of acalabrutinib, venetoclax, and rituximab (AVR) in treatment-naive mantle cell lymphoma (TN MCL). Patients received acalabrutinib from cycle 1 until progressive disease (PD) or undue toxicity, rituximab for 6 cycles with maintenance every other cycle through cycle 24 or until PD, and venetoclax, beginning at cycle 2, for 24 cycles. Twenty-one patients were enrolled; 95.
View Article and Find Full Text PDFChronic lymphocytic leukemia (CLL) progression during Bruton tyrosine kinase (BTK) inhibitor treatment is typically characterized by emergent B-cell receptor pathway mutations. Using peripheral blood samples from patients with relapsed/refractory CLL in ELEVATE-RR (NCT02477696; median 2 prior therapies), we report clonal evolution data for patients progressing on acalabrutinib or ibrutinib (median follow-up, 41 months). Paired (baseline and progression) samples were available for 47 (excluding 1 Richter) acalabrutinib-treated and 30 (excluding 6 Richter) ibrutinib-treated patients.
View Article and Find Full Text PDFBefore targeted therapies, patients with higher-risk chronic lymphocytic leukemia (CLL), defined as del(17p) and/or TP53 mutation (TP53m), unmutated immunoglobulin heavy chain variable region genes (uIGHV), or complex karyotype (CK), had poorer prognosis with chemoimmunotherapy. Bruton tyrosine kinase inhibitors (BTKis) have demonstrated benefit in higher-risk patient populations with CLL in individual trials. To better understand the impact of the second-generation BTKi acalabrutinib, we pooled data from 5 prospective clinical studies of acalabrutinib as monotherapy or in combination with obinutuzumab (ACE-CL-001, ACE-CL-003, ELEVATE-TN, ELEVATE-RR, and ASCEND) in patients with higher-risk CLL in treatment-naive (TN) or relapsed/refractory (R/R) cohorts.
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- - The study investigated how arterial hypertension (AH) affects long-term outcomes in patients with diffuse large B-cell lymphoma (DLBCL), using data from the Polish Lymphoma Research Group.
- - Findings showed that 28% of patients had pre-existing AH, which significantly lowered overall survival rates and led to much higher cardiovascular deaths compared to those without AH.
- - The results suggest that AH is a strong, independent predictor of premature cardiovascular mortality, indicating the need for increased monitoring in cardio-oncology practices.
Article Synopsis
- The phase 3 ASPEN trial compared the effectiveness of two BTK inhibitors, zanubrutinib and ibrutinib, in treating Waldenström macroglobulinemia, analyzing genetic mutations' impact on treatment response.
- The study found that patients with mutations in CXCR4 and TP53 had poorer responses and survival rates but those treated with zanubrutinib generally showed better outcomes than those given ibrutinib.
- Overall, the research indicated that zanubrutinib offers improved clinical outcomes for patients with specific mutations compared to ibrutinib, highlighting the importance of genetic testing in treatment decision-making.
Article Synopsis
- Parsaclisib is a selective inhibitor targeting PI3Kδ that has shown promise for patients with relapsed or refractory B-cell lymphomas, particularly marginal zone lymphoma (MZL).
- The CITADEL-204 phase 2 study evaluated its efficacy and safety in patients who had prior treatment with BTK inhibitors and those who were treatment-naive, focusing on objective response rates (ORR) as the primary endpoint.
- The study found a 58.3% ORR in the daily dosing group, with a median response duration of 12.2 months, although some patients experienced significant treatment-related side effects such as diarrhea and neutropenia, leading to dose modifications in a large number of cases.
Article Synopsis
- * The study included 80 patients, revealing an objective response rate of 57.5% and a complete response rate of 41.3%, with a median overall survival of 33.5 months over a follow-up period averaging 65.6 months.
- * Adverse events were manageable and decreased during tafasitamab monotherapy, indicating a generally tolerable safety profile consistent with earlier reports.
Background: Parsaclisib is a potent and highly selective PI3Kδ inhibitor that has shown clinical benefit in patients with relapsed/refractory (R/R) B-cell malignancies. In this phase 2 study (CITADEL-205; NCT03235544, EudraCT 2017-003148-19), the efficacy and safety of parsaclisib was evaluated in patients with R/R mantle cell lymphoma (MCL).
Methods: Patients ≥18 years old with pathologically confirmed R/R MCL and prior treatment with 1-3 systemic therapies, with (cohort 1) or without (cohort 2) previous Bruton kinase inhibitor (BTKi) treatment, received oral parsaclisib 20 mg once-daily (QD) for 8 weeks, then either parsaclisib 20 mg once-weekly (weekly dosing group [WG]) or parsaclisib 2.
Article Synopsis
- The phase III ASPEN study showed that zanubrutinib is as effective as ibrutinib but has better safety for treating patients with Waldenström macroglobulinemia (WM).
- In a long-term follow-up, zanubrutinib demonstrated higher rates of very good partial response and complete response compared to ibrutinib in both cohorts of WM patients.
- Adverse events like diarrhea, muscle spasms, and hypertension were more common with ibrutinib, while zanubrutinib had a lower risk of treatment-related discontinuation.
Article Synopsis
- Patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) often struggle after failing treatment with covalent BTK inhibitors, prompting the need for new options like pirtobrutinib, a selective noncovalent BTK inhibitor designed to resume BTK inhibition.* -
- In a phase 1-2 trial involving 317 patients, 73.3% responded positively to pirtobrutinib, with a notable 82.2% response rate when including those showing partial responses with lymphocytosis; the median progression-free survival was reported at 19.6 months.* -
- Common side effects from pirtobrutinib treatment included infections (71%),
ELEVATE-RR demonstrated noninferior progression-free survival and lower incidence of key adverse events (AEs) with acalabrutinib vs ibrutinib in previously treated chronic lymphocytic leukemia. We further characterize AEs of acalabrutinib and ibrutinib via post hoc analysis. Overall and exposure-adjusted incidence rate was assessed for common Bruton tyrosine kinase inhibitor-associated AEs and for selected events of clinical interest (ECIs).
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- * Conducted as a nonrandomized phase I/II trial, the study involved 11 patients, with different treatment regimens in two arms: ceralasertib alone or combined with acalabrutinib.
- * Results showed significant adverse effects in the ceralasertib monotherapy group, including high rates of anemia and thrombocytopenia, while the combination therapy displayed better outcomes with a 100% response rate and no severe toxic