Leukemia
Bruton’s tyrosine kinase inhibition in CLL: present and future
BTK inhibitors have been important game changers in the management of B-cell lymphoma in general and B-CLL and small lymphocytic lymphoma in particular. Federico Pea, MD, University of Bologna, Italy, discussed differences between the irreversible BTK inhibitors ibrutinib, acalabrutinib and zanubrutinib. The second-generation drugs acalabrutinib and zanubrutinib demonstrated higher kinase selectivity than the first-in-class agent ibrutinib, which implies an improved efficacy-toxicity ratio.
Real-world risk assessment, outcomes and adoption of novel drugs in CLL patients: insights from US databases
Prognostic testing including IGHV mutation status, cytogenetic abnormalities by FISH, and immunophenotyping has been recommended after diagnosis of CLL/SLL prior to treatment initiation. This also applies to previously treated patients in some settings. As disease with high-risk genetic features is better managed with novel agents than with chemoimmunotherapy, the need for testing has recently become more relevant as all patients are advised to complete risk-factor testing for both prognostication and selection of optimal, evidence-based therapy.
Promising novel approaches in various B-cell malignancies
For more than 20 years, the R-CHOP regimen consisting of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone has been the standard of care in the first-line treatment of diffuse large B-cell lymphoma (DLBCL). However, as only 60-70 % of patients achieve cure, there is a need to improve on these results. The antibody-drug conjugate polatuzumab vedotin that targets CD79b has already shown activity in combination with rituximab or obinutuzumab plus cyclophosphamide, doxorubicin, and prednisone (CHP) in a phase II study conducted in the first-line setting of DLBCL.
Management of patients with relapsed/refractory CLL: what is new?
The optimal novel-agent approach for patients with chronic lymphocytic leukemia (CLL) is subject to research. Targeted therapies have become the undisputed standard of care in both relapsing/refractory and treatment-naïve settings. The choice of regimen remains, however, disputable. Continuous BTK inhibition confers the risk of cumulative toxicity and acquired resistance, while time-limited combination therapies may result in relatively high adverse event (AE) rates and lead to overtreatment of patients with favorable risk.
Determining first-line CLL/SLL treatment strategies with optimized efficacy and safety
The international, randomized, phase III GAIA/CLL13 study was conducted to identify the optimal time-limited first-line treatment regimen for fit patients with chronic lymphocytic leukemia (CLL). Standard chemoimmunotherapy (CIT) consisting of fludarabine, cyclophosphamide and rituximab (FCR; patients ≤ 65 years) or bendamustin plus rituximab (BR; patients > 65 years) was compared to venetoclax-based, limited-duration strategies.
Successful inhibition of PI3K, BTK, BCL2 and other targets in various B-cell malignancies
Rituximab monotherapy is a recognized standard of care in patients with relapsed indolent non-Hodgkin lymphoma (iNHL) who have had long remissions after rituximab-based therapy or who are unwilling or unfit to be treated with chemotherapy. However, the clinical benefit conferred by rituximab can be limited due to drug resistance.
CLL/SLL: current perspectives across a range of potent agents
The introduction of effective inhibitors of B-cell receptor signaling such as the BTK inhibitor ibrutinib has transformed the treatment of patients with chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). The irreversible, potent, next-generation BTK inhibitor zanubrutinib has been designed to maximize BTK occupancy and minimize off-target inhibition of other kinases.