CLL Research Review Club

First-Line Venetoclax Combinations in Chronic Lymphocytic Leukemia

In this large randomized phase 3 clinical trial (CLL13/GAIA), previously untreated patients with chronic lymphocytic leukemia (CLL) with a median age of 61 years were randomly assigned (1💯1:1) to treatment on one of the following four arms: 1) chemoimmunotherapy (CIT) consisting of either fludarabine, cyclophosphamide and rituximab (FCR) or bendamustine and rituximab (BR; patients <65 years received FCR and those over 65 years received BR); 2) venetoclax-rituximab; 3) venetoclax-obinutuzumab; or 4) ibrutinib-venetoclax-obinutuzumab.

Zanubrutinib or Ibrutinib in Relapsed or Refractory Chronic Lymphocytic Leukemia

In this randomized phase 3 study, 652 patients with relapsed chronic lymphocytic leukemia were randomly assigned to treatment with either zanubrutinib or ibrutinib. The median age of patients who enrolled in the study was 67 years. Deletion 17p was noted in 23% patients, and IGHV genes were unmutated in 73% patients.

Pirtobrutinib after a Covalent BTK Inhibitor in Chronic Lymphocytic Leukemia

In this phase 1/2 clinical trial, patients with relapsed or refractory B-cell malignancies received pirtobrutinib, a novel noncovalent Bruton tyrosine kinase inhibitor (BTKi). A total of 317 patients with CLL or SLL were treated, including 247 who had previously received a covalent BTK inhibitor. In addition, approximately 40% of patients had also received treatment with venetoclax previously.

About the Reviewer

Sameer A. Parikh, M.B.B.S.

Associate Professor of Medicine

Assistant Professor of Oncology

Sameer A. Parikh, M.B.B.S., is a consultant in the Division of Hematology, Department of Internal Medicine at Mayo Clinic in Rochester, Minnesota. He joined the staff of Mayo Clinic in 2014 and holds the academic rank of associate professor of medicine and assistant professor of oncology, Mayo Clinic College of Medicine and Science. He currently serves as the Chair of the CLL Disease Team at the Mayo Clinic Comprehensive Cancer Center.

Dr. Parikh earned his Bachelor of Medicine and Surgery at the University of Mumbai – Seth G. S. Medical College in Mumbai, India. He completed his residency at St. Francis Hospital, University of Illinois at Chicago and a fellowship in leukemia at University of Texas, M.D. Anderson Cancer Center in Houston. He subsequently completed a hematology/oncology fellowship at Mayo Clinic School of Graduate Medical Education in Rochester, MN.

Dr. Parikh’s research focuses on lymphoproliferative disorders, particularly chronic lymphocytic leukemia (CLL). He is a Principal Investigator of several investigator-initiated and industry-sponsored clinical trials. He is also the Principal Investigator of the Mayo Clinic CLL Database, which includes all patients with a diagnosis of CLL seen in the Division of Hematology at Mayo Clinic in Rochester, MN since 1995, and which is linked to the Mayo Clinic CLL Tissue Bank. He is also a co-investigator on many studies that are funded by the National Institutes of Health and the National Institute on Aging. He has given presentations both nationally and internationally and has authored >100 journal articles, book chapters and other publications.

Dr. Parikh is a recipient of numerous awards, including the Shannon Timmins Leukemia Fellowship Award, ASCO Merit Award, Mayo Clinic Department of Medicine Career Development Award, Lymphoma SPORE Career Development Award, Mayo Clinic Paul Calabresi Program in Translational Research Scholar Award (K12 CA090628), and the Mayo Clinic K2R Career Development Award.

In addition to his clinical and research activities, Dr. Parikh is active in education and has served as a mentor to many residents and fellows, among other learners. Dr. Parikh is an active member of the American College of Physicians, American Society of Clinical Oncology, American Society of Hematology, and the Eastern Co-operative Oncology Group (ECOG-ACRIN). He serves as the Mayo Clinic representative on the National Comprehensive Cancer Network (NCCN) CLL/SLL/hairy cell leukemia panel. He also serves on the Medical Advisory Board of the CLL Society, a not-for-profit organization dedicated to address unmet needs of CLL patients through education, advocacy, support, and research.