Chronic Lymphocytic Lymphoma | Professor Dr Stephan Stilgenbauer

Chronic Lymphocytic Lymphoma, Issue 2, 2019 — Part 1: Our interview with Prof Stilgenbauer highlights the following topics as well as cases from his practice: Updated International Workshop on Chronic Lymphocytic Leukemia guidelines for diagnosis, indications for treatment, response assessment and management of chronic lymphocytic leukemia (CLL) (00:00) Genetic abnormalities in CLL; effects of p53 mutations and 17p deletion on prognosis and therapy (02:48) Design and eligibility for the Phase III CLL14 trial of venetoclax/obinutuzumab versus chlorambucil/obinutuzumab for patients with previously untreated CLL and coexisting medical conditions (05:42) Recent data from the Phase III iLLUMINATE, Alliance A041202 and ECOG-E1912 trials comparing ibrutinib-based regimens to chemoimmunotherapy as first-line treatment for patients with CLL (07:51) Results from the CLL14 trial comparing venetoclax to chlorambucil as an addition to fixed-duration obinutuzumab therapy for CLL (10:17) Management of disease relapse on the CLL14 trial; role of minimal residual disease (MRD) assessment in therapeutic decision-making (13:19) Dosing and administration of the recently FDA-approved first-line regimen of venetoclax and obinutuzumab; mitigation of risk for tumor lysis syndrome (16:03) Mechanism of action of venetoclax; role of renal function in the decision to administer this agent (17:02) Emerging data with the combination of ibrutinib or venetoclax with anti-CD20 antibodies (20:05) Del(17p) and/or p53 mutation status and the selection of therapy for patients with CLL (22:09) Role of bendamustine/rituximab in the management of CLL (26:43) Perspective on the efficacy of venetoclax/obinutuzumab versus ibrutinib as first-line therapy for patients with CLL (28:38) Case: A man in his mid-60s with del(17p) CLL and no IGHV mutation experiences a dramatic response to first-line ibrutinib (30:42) Prolonged lymphocytosis during ibrutinib therapy (33:20) Clonal evolution in CLL; importance of monitoring for del(17p) and p53 mutations before treatment initiation (35:35) Sequencing of ibrutinib and venetoclax for patients with CLL; tolerability and quality of life with ibrutinib versus venetoclax (36:59) Management of arthralgias associated with Bruton tyrosine kinase (BTK) inhibitors (40:25) Case: A woman in her mid-70s with del(13q) CLL and no IGHV mutation receives acalabrutinib after experiencing disease progression on multiple lines of therapy, including ibrutinib (42:15) BTK inhibitor-associated headaches and atrial fibrillation (44:18) Efficacy of ibrutinib versus acalabrutinib; ongoing Phase III ACE-CL-006 study comparing acalabrutinib to ibrutinib for previously treated, high-risk CLL (47:31) Case: A man in his late 70s with del(11q) CLL and no IGHV mutation attains a complete response and MRD-negative status with venetoclax and obinutuzumab on the Phase III CLL14 trial (51:59) Side effects of venetoclax/obinutuzumab (53:36) Case: A man in his early 70s with hairy cell leukemia (HCL) and a BRAF mutation experiences disease progression after receiving vemurafenib as second-line therapy (57:25) Activity and tolerability of the recently FDA-approved antibody-drug conjugate moxetumomab pasudotox-tdfk in patients with relapsed/refractory HCL (59:10) Novel approaches under investigation for HCL (1:01:11) Case: A woman in her late 50s develops Richter’s transformation (RT) from CLL to diffuse large B-cell lymphoma (DLBCL) after receiving ibrutinib as second-line therapy (1:03:52) Pathogenesis and frequency of RT in patients with relapsed/refractory CLL (1:06:45) Comparison of the biology of Richter’s transformed versus de novo DLBCL; novel therapies under investigation for RT (1:10:06) CME information and select publications