Dr. Julie Vose on Time-Limited Therapy and Other Strategy Shifts in CLL

Julie Vose, MD, chief of the Division of Oncology and Hematology at the University of Nebraska Medical Center, joined Blood Cancers Today to discuss the main takeaways from the chronic lymphocytic leukemia (CLL) session at the 2025 Pan Pacific Leukemia Conference on July 15–18 in Lahaina, Hawaii.

Dr. Vose outlined the most significant shifts in CLL treatment, including time-limited therapy, the challenges of managing Richter’s transformation, and how she makes individualized treatment decisions for patients with CLL based on age and mutation status.

Given the rapid evolution of targeted therapies, what are the biggest factors influencing choice of first-line treatment for young versus older patients with CLL?

The biggest influencers are the genetics of the CLL. Do they have a TP53 mutation? Do they have unmutated disease? Of course, there’s the overall wishes for the patient as far as being on long-term oral medication versus time-limited therapy. Thankfully, most patients don’t have to use chemotherapy anymore. It’s more a question of immunotherapy with different oral medications, including BTK [Bruton tyrosine kinase] inhibitors and BCL2 [B-cell lymphoma 2] inhibitors. It’s more about working with the patient to understand their needs and reviewing their insurance to ensure they can be covered for whatever treatment we recommend. It’s a lot of personalized care.

How do you see treatment sequencing strategies changing as more patients become double refractory to some of the current standards of care?

The minority of patients so far have become double refractory, but as time goes on, that may change. Currently for double refractory patients, we would check the genetics for the CLL and see if they’ve changed from the original ones. CAR [chimeric antigen receptor] T-cell therapy is an opportunity for those patients, as well as bispecific antibodies.

I think there will be a lot more new developments as more of those patients become double refractory. It’s not a huge problem right now, but I can see down the line where that may be, and we’ll need other alternatives.

Richter’s Transformation remains a significant challenge. What promising approaches or clinical trials are on the horizon that may change the way you manage this?

Richter’s transformation is still an unmet medical need. Typically, we would treat those patients like a de novo diffuse large B cell lymphoma, possibly with CLL-directed therapy depending on the situation. If it’s a younger patient, we can get them into remission, then an allergenic transplant could still be an option for those patients.

Which biomarkers or patient characteristics are proving most valuable in guiding individualized treatment in CLL?

It would be FISH [fluorescence in situ hybridization] testing to see if they have a TP53 mutation, plus the TP53 mutation itself, as well as the immunoglobulin heavy chain gene rearrangement. The latter only needs to be checked once, and the patient never changes, but the CLL FISH does need to be checked with each subsequent progression or as time has gone on, when they need treatment to make sure it hasn’t changed.

Looking five years ahead, what do you anticipate will be the biggest shifts in CLL therapy? What hurdles need to be addressed to get there?

Using time-limited therapy in appropriate patients is a big shift. I also think checking for minimal residual disease or ctDNA may be a big shift in trying to utilize that strategy or other strategies to see if we can limit the therapy for patients. Nobody wants to be on therapy long-term if they can help it, certainly from the toxicity profile and cost profile. If we can figure out ways for more people to access time-limited therapy, whether that involves extending the duration or adding an agent. That’s one of the big goals we should have.

What is your main takeaway from the CLL session at the Pan Pacific Leukemia Conference?

The biggest takeaway is that we need to individualize care, and considering the genetic profile of CLL, as well as the patient’s wishes, is crucial. These patients typically live for a very long time, and we need to make sure that we plan for the long term and that we’re not causing more side effects without helping the patients. We must always balance side effects, the cost of the agent, and the treatment of the disease.