Case 4: Maintenance Strategies in CLL



William Wierda, MD, PhD:So, this is a young patient. She received FCR, achieved a complete remission, and is MRD-positive. She’s going to relapse. She’s probably going to have a longer progression-free survival than, perhaps, the patient who has an unmutated V gene that is MRD-positive. But the fact that she’s MRD-positive puts her at a higher risk for progression. I think that we should probably touch on maintenance strategies because there are data that support maintenance for this type of patient. There are data for lenalidomide as a maintenance strategy and CD20 antibodies—both rituximab and ofatumumab.

There are 3 randomized phase III trials looking at progression-free survival. The trials have clearly demonstrated improvements in progression-free survival for patients who have received a maintenance therapy (whether it’s lenalidomide monotherapy or CD20 antibody monotherapy), with a hazard ratio of 0.4 to 0.5 for progression-free survival. None of these trials have shown improvements in overall survival, and all the treatments have been associated with some increased risk for toxicity. Whether it’s lenalidomide or a CD20 antibody, there are immune effects and an increased risk for infection. There clearly is an increase in infectious events for patients who are receiving maintenance therapy.

We don’t typically do maintenance therapy for patients, whether it’s lenalidomide or a CD20 antibody. There are a couple of instances where I have given CD20 as maintenance—particularly in patients who have been in remission and have had issues with autoimmune phenomena. I’ll put them on an extended course of maintenance CD20 antibody, whether it’s rituximab or ofatumumab. That will reduce the risk for recurrent autoimmunity phenomena and, perhaps, extend progression-free survival. Matt, what are your thoughts on maintenance therapy?

Matthew S. Davids, MD, MMSc:We don’t typically use maintenance therapies for patients with CLL . Sometimes it’s tempting to extrapolate from other indolent non-Hodgkin lymphomas, where there may be more benefits, for example, with rituximab maintenance. But unfortunately, the data in CLL don’t support an overall survival benefit. And even if there are some progression-free survival benefits, I think it’s always important to think about the patient population that’s been studied. Some of the randomized studies that you alluded to were for patients who had been through 2 or 3 prior lines of chemoimmunotherapy. Then they were put on a CD20 antibody. These are just not the patients that we’re seeing very often. We’re typically treating these patients with novel agents, and I think that’s probably a better way to go after chemoimmunotherapy.

William Wierda, MD, PhD:Thank you, Matt. Thank you Dr. Bagg, Dr. Davids, and Dr. Jain, for your thoughtful case presentations and a very lively, informative discussion. To our viewing audience, thank you for joining us for thisTargeted OncologyTMVirtual Tumor Board®presentation. We hope today’s discussion was a valuable use of your time and that you acquired some practical knowledge that you can take back to your clinic.

Transcript edited for clarity.

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