Second-Line Treatment Options for Relapsed CLL


An expert in the management of chronic lymphocytic leukemia discusses how patient- and disease-related factors influence treatment decisions after relapse.

Jeff Sharman, MD: After first-line treatment, the trigger to start therapy in the second line is really the same as the first line. We’re looking for a rapid rise in white blood cell count, which is doubling in less than 6 months. We’re looking for emergence of bone marrow dysfunction: recurrent anemia or thrombocytopenia. We’re looking for symptomatic bulky lymph nodes, and when we’re thinking about treatment in the relapse setting, oftentimes the most important question is: What did they get in the first-line setting?

For a patient who had a BTK [Bruton tyrosine kinase] inhibitor and has demonstrated progression, your options at that point are going to be venetoclax [Venclexta] basic therapy or a PI3 kinase therapy. When I’m thinking about patients for venetoclax, the things that come to mind are the risks for tumor lysis and the patient’s ability to navigate the ramp-up. With regard to tumor lysis, this patient had lymph nodes in excess of 5 cm. I believe her white blood cell count was elevated as well, so she would be at high risk for tumor lysis. Adding that she has a depressed creatinine clearance with a GFR [glomerular filtration rate] of 40 mL/min, she’s really at high risk. This is a patient who would need to be hospitalized for the first dosages of the 20-mg and 50-mg dose level for venetoclax.

Furthermore, there’s a lot of back and forth. This requires a lot of monitoring, and not every 76-year-old is capable of navigating that robustly. Sometimes the simplicity of starting a PI3 kinase inhibitor can be quite appealing to a patient. Oftentimes, a second-line therapy after BTK would be a venetoclax-based regimen. However, you have to be looking out for those patients for whom venetoclax may be particularly tricky or difficult. One such patient would have decreased glomerular filtration rate, bulky nodes, and an elevated white blood cell count. There’s a lot to be said about the simplicity of idelalisib [Zydelig] and rituximab [Rituxan]. Picking among the PI3 kinase inhibitors, you have 2 choices: idelalisib or duvelisib [Copiktra]. This patient has never had an anti-CD20 protein therapy. In those patients, I oftentimes with go with idelalisib in combination with rituximab. If somebody is anti-CD20 refractory, that may be a patient where I can use duvelisib.

One of the interesting features is that 17p is an adverse prognostic characteristic for those patients treated with venetoclax. That’s true in the frontline setting. It’s also true in the relapsed/refractory setting. Interestingly, among all the novel agents, idelalisib is the only 1 that has demonstrated equal outcomes among patients with 17p and without. They don’t have an adverse outcome when treated with idelalisib. We don’t know why, but it’s an observation. It stood up through prolonged follow-up of the pivotal study.

For this patient, idelalisib-rituximab could be very useful. That study was originally designed for patients who were treated with rituximab alone vs rituximab and idelalisib. We think about the Cumulative Illness Rating Scale [CIRS]. That’s a numerical evaluation of something we do quite often—we call it the eyeball test. But this allows us to have a numerical evaluation of it. The Cumulative Illness Rating Scale assigns points for various comorbidities. The higher somebody’s score is, the more chronically and medically ill they are. This was a study designed for patients who had an elevated CIRS score, for whom rituximab monotherapy may have been considered. It’s a little hard to imagine that study design now. I don’t remember exactly when that study was launched; I think it was 2011 or so. It was read out it in 2014. It shows a bit of our historical perspective on these things.

This transcript has been edited for clarity.

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