Treatment with ibrutinib, fludarabine, cyclophosphamide, and obinutuzumab (iFCG) showed promise as a first-line treatment for patients with chronic lymphocytic leukemia and mutated IGHV and without TP53 aberrations, according to findings from a phase 2 trial.

“FCR has been the standard firstline treatment for young patients (pts) with CLL with a complete response rate after 6 cycles of 40-72%, and undetectable bone marrow (BM) MRD (U-MRD) rate after 6 cycles of 43-58%,” Nitin Jain, MD, associate professor in the department of leukemia at The University of Texas MD Anderson Cancer Center, and colleagues wrote. “However, there is up to 5% long-term risk of t-MDS/AML. ...We developed a CIT-based regimen of finite duration that included ibrutinib and obinutuzumab. The intent was to limit chemotherapy to 3 cycles, potentially reducing short- and long-term toxicity, while increasing efficacy through the addition of ibrutinib and a more potent CD20 antibody (obinutuzumab) and achieving durable, therapy-free remission.”

Leukemia cells. Source: Getty

Forty-three patients with CLL and mutated IGHV without TP53 aberrations began therapy between March 2016 and April 2018. One patient was later re-categorized as not having an IGHV mutation. Median follow-up was 18.6 months.

All of the remaining 42 patients achieved a response at 3 months, with 17 attaining complete remission (CR) or complete remission with incomplete marrow recovery (CRi) and 25 achieving partial remission. Further, 90% achieved undetectable bone-marrow MRD at 3 months. Overall, 40.4% of patients (n = 17) achieved CR or CRi with undetectable bone-marrow MRD at 3 months.

These responses improved over time. At 12 months, with 28 patients remaining, all patients had undetectable bone-marrow MRD and ceased ibrutinib in keeping with protocol. After a median of 10.1 months of follow-up, all 28 maintained their MRD status.

One 26-year-old patient with no cardiac history developed congestive heart failure during cycle 9 of treatment and died.

“iFCG achieves high rate of U-MRD in previously-untreated patients with CLL with IGHV-M CLL,” the researchers wrote. “No patient has progressed and all patients who have stopped ibrutinib maintain undetectable bone-marrow MRD status.”