Chemoimmunotherapy Regimen Under Study in Younger Patients With CLL
Posted: Friday, September 11, 2020
Younger, fit patients with chronic lymphocytic leukemia (CLL) may wish to pursue more aggressive treatment approaches in the hope of achieving a cure with time-limited therapy. In this patient population, long-term remissions have been shown with the chemotherapy regimen FCR (fludarabine, cyclophosphamide, rituximab); now Jennifer R. Brown, MD, PhD, of Dana-Farber Cancer Institute, Boston, and colleagues are studying the addition of the PI3K delta/gamma inhibitor duvelisib to the treatment mix to prolong survival across CLL prognostic groups. The early findings of their phase Ib/II trial, which were published in Leukemia, suggest activity with this combination therapy, although the 3-year progression-free survival of 73% is not superior to that of FCR alone.
“If duvelisib plus FCR were to be studied further, strategies that include a shorter course of FCR and other approaches to mitigate toxicity while maintaining efficacy would need to be explored,” proposed the study authors.
A total of 32 patients with CLL up to age 65 were enrolled in the study. In the setting of initial therapy, two dosing schedules of duvelisib were included: 25 mg daily and 25 mg twice daily. One week of duvelisib was followed by standard FCR, for up to 6 cycles of 28 days, and then up to 2 years of duvelisib maintenance therapy. The schedule of 25 mg twice daily was identified as the phase II dose.
On intention-to-treat analysis, the best overall response rate was 88%, with 56% being the rate of complete remission or complete remission with incomplete hematologic recovery. In addition, 66% was the best rate of bone marrow–undetectable minimal residual disease. The 3-year progression-free and overall survival rates were 73% and 93%. In terms of toxicity, hematologic side effects were common; transaminitis, febrile neutropenia, pneumonia, and colitis were among the all-grade nonhematologic adverse events reported.
Disclosure: For full disclosures of the study authors, visit nature.com.
