Welcome. My name is Dr. Edward Crane. I am a hematologist oncologist at TriHealth Cancer Institute based in Cincinnati, Ohio. Thank you for joining me as I share with you an application of VENCLEXTA in relapsed or refractory chronic lymphocytic leukemia, or CLL, based on the data from the MURANO trial. VENCLEXTA is a BCL-2 inhibitor indicated for the treatment of adult patients with chronic lymphocytic leukemia or small lymphocytic lymphoma. ¹ Let’s take a look at the clinical application of the VEN+R regimen.

This is Mark, a 72-year-old Caucasian male—a typical patient who might show up at your practice. He lives in the city with his wife and two dogs. He enjoys hiking and volunteers at a local animal shelter a couple times a week. Two years ago, Mark was diagnosed with Rai stage I CLL and was treated with six cycles of FCR. He completed first-line therapy and achieved a complete remission. Sixteen months following the completion of the first-line treatment, Mark complained of swollen neck, fever, and more than 10 pounds of weight loss within one month. Mark returned to his hematologist. Since Mark’s initial diagnosis, his complete blood count has been routinely measured. In the last three months, his absolute lymphocyte count, or ALC, remained higher than the upper limits of normal and in his most recent test, his ALC was 38.6x10⁹/L. Mark’s platelet count was low and his renal function showed a mild decline. Mark’s hematologist saw no evidence of chromosome 17p deletion as measured by fluorescent in situ hybridization, or FISH, but did see atypical cells in his peripheral blood smear. Considering Mark’s test results and physical exam, he was diagnosed with Rai stage II CLL, consistent with a medium tumor burden. The National Comprehensive Cancer Network^® (NCCN^®) recommends venetoclax (VENCLEXTA^®) in combination with rituximab as a Category 1 preferred regimen for the treatment of R/R CLL/SLL patients with or without 17p deletion. ¹¹

Based on Mark’s diagnosis and test results, his hematologist recommended treatment with VEN+R. To decrease the risk of TLS and prior to starting Cycle 1 of VEN+R, VEN monotherapy is ramped up over the course of 5 weeks starting at 20 mg/day, increasing weekly, and reaching a peak of 400 mg/day in Week 5. Mark's physician had him undergo the recommended hydration, prophylaxis, and monitoring measures while starting VENCLEXTA. Mark did not show signs or symptoms of TLS, nor did he experience any other adverse reactions during the ramp-up period. After the dose ramp-up, Mark will take 24 months of VENCLEXTA daily at 400 mg/day and 6 cycles of rituximab with 375 mg/m² in Cycle 1 and 500 mg/m² in Cycles 2-6. On Week 3 of the combination treatment period, Mark experienced Grade 3 neutropenia, Grade 1 fever, and Grade 1 diarrhea. Since this was the first occurrence of Grade 3 neutropenia for Mark, treatment with VEN+R was interrupted. One week later, neutropenia resolved to Grade 1, and VEN+R was resumed at the same dose. If Grade 3 neutropenia with infection or fever occurred again, VEN+R treatment would need to be interrupted again, and dose reduction guidelines for VENCLEXTA would need to be observed prior to resuming treatment. Granulocyte-colony stimulating factor, or G-CSF, should also be considered if clinically indicated. Mark will continue treatment with VEN+R until completion of treatment at 24 months, unless there is disease progression or unacceptable toxicity.

Upon completion of his treatment regimen, Mark will have no additional exposure to VEN+R. During his treatment, Mark shared with his physician that he was looking forward to the possibility of a treatment-free period and he appreciated that this was a fixed-duration, fixed-cost regimen. AbbVie and Genentech would like to thank all of the patients and their families, investigators, and clinical study sites from across the country who were involved with the MURANO trial. I would also like to thank you for joining me in exploring the activity of the fixed duration VENCLEXTA + rituximab regimen for patients with R/R CLL.