Sometimes despite our best efforts, chronic lymphocytic leukemia (CLL) returns after a period of successful treatment (relapse) or stops responding to treatment (refractory). The decision on what to do next will depend on several factors including the number of previous treatments, the type of previous treatments, genetic abnormalities, overall health, and the aggressiveness of the cancer.
Relapsed/refractory CLL can be difficult to treat, and scientist are investigating the idea that using combination therapies in relapsed/refractory patients will produce higher response rates and deeper remissions with undetectable minimal residual disease (uMRD). A phase III clinical trial of the combination of venetoclax + rituximab showed extremely promising results for treating relapsed/refractory CLL, but it also involved 2 years of continuous treatment with an infusional component. Researchers are interested in developing other treatment regimens which can be taken orally and are time-limited in duration.
At the annual meeting of the American Society of Hematology (ASH) 2020, our own Steven Bloom interviewed Dr. Jennifer Brown, Director of the CLL Center at Dana-Farber Cancer Institute and Professor of Medicine at Harvard Medical School. They discussed preliminary results from an ongoing phase I/II clinical trial of duvelisib + venetoclax for patients with relapsed/refractory CLL or Richter’s syndrome.
- This trial is testing the safety and efficacy of duvelisib (a PI3K inhibitor) + venetoclax (a Bcl2 inhibitor) for patients with relapsed/refractory CLL or Richter’s syndrome.
- Thus far, 22 patients have enrolled in the trial.
- Approximately 2/3 of patients had previously taken a Bruton’s tyrosine kinase (BTK) inhibitor, and the median number of prior therapies was 3.
- Patients were treated with a 7-day lead-in of duvelisib followed by venetoclax ramp-up. Patients then received 12 cycles of combination duvelisib + venetoclax.
- After 12 cycles, patients with uMRD could discontinue while patients with persistent MRD continued on venetoclax.
- Preliminary data shows that ~50% of patients experienced complete remission with uMRD in the peripheral blood and bone marrow.
- Some patients (6 out of 22) had to discontinue duvelisib due to side effects (diarrhea) but continued with venetoclax.
- More recently, researchers have started testing combination duvelisib + venetoclax in patients with Richter’s syndrome, and this work is ongoing.
- Targeted therapy combinations are mainly considered for patients with Richter’s syndrome who have failed frontline chemotherapy.
Though this trial is still ongoing, the preliminary results thus far look encouraging with half of patients achieving complete remission with uMRD. The safety profile looks manageable, although not all patients may be able to tolerate the regimen. Researchers are constantly looking for new ways to help patients with relapsed/refractory CLL who have already tried a number of different therapies, and this research provides another tool in the toolbox.
Please enjoy this interview with Dr. Brown from the virtual ASH meeting which was held December 2020.
You can read the actual ASH abstract here: Updated Results from a Phase I/II Study of Duvelisib and Venetoclax in Patients with Relapsed or Refractory CLL / SLL or Richter’s Syndrome
Take care of yourself first.
Ann Liu, PhD