Results from a sub-analysis of the phase 2 RESONATE-17 study has shown Ibrutinib ( Imbruvica ) was associated with robust efficacy and a positive risk-benefit profile in patients with relapsed or refractory chronic lymphocytic leukemia or small lymphocytic lymphoma ( CLL/SLL ) who have the genetic alteration del 17p. Notably, Ibrutinib was associated with a high overall response rate ( Independent Review Committee [ IRC ]-assessed ORR; the primary endpoint ) and long progression-free survival ( PFS ) across a variety of baseline genetic characteristics or mutations.
These data were presented at the 2015 American Society of Hematology ( ASH ) meeting in Orlando ( Florida, United States ).
Chronic lymphocytic leukemia patients with the genetic alteration del 17p are considered to be high risk and typically have poor prognoses. Imbruvica was the first therapy approved specifically for this difficult-to-treat patient population and the positive data seen in this analysis reinforce its clinical utility in CLL patients with del 17p.
RESONATE-17 is one of the largest dedicated studies conducted in patients with relapsed or refractory chronic lymphocytic leukemia with del 17p. The study evaluated 144 previously treated patients with del 17p ( 137 with chronic lymphocytic leukemia, seven with SLL ), who received single-agent Ibrutinib once daily until progression or unacceptable toxicity.
A total of 116 patients were determined to have baseline genetic characteristics with the potential to influence treatment outcomes.
The primary endpoint of the open-label, single-arm, multi-center trial was ORR, as measured by the IRC. Duration of response ( DOR ), progression-free survival and safety were key secondary endpoints.
At the time of the data assessment, the median treatment duration was 11.1 months and 70% of people continued treatment with Ibrutinib.
After a median follow-up of 11.5 months, the investigator-assessed ORR including partial response with lymphocytosis ( PR-L ) for all treated patients was 83% in the RESONATE-17 trial; specifically, 17% of patients experienced a PR-L.
While median progression-free survival and overall survival were not yet reached, the 12-month progression-free survival and overall survival rates were 79% and 84%, respectively. Overall, results were consistent across subgroups with additional baseline characteristics or mutations ( e.g., del 11q, del 13q, NOTCH1, TP53, etc. ).
Imbruvica was the first therapy to be approved by the FDA specifically for CLL patients with the del 17p genetic alteration. The RESONATE-17 trial is one of the largest prospective trials ever conducted solely in this patient population, whose outcome is usually quite poor when treated with available therapies.
The most common adverse events ( greater than or equal to 20% ) of any grade included diarrhea ( 36% ), fatigue ( 31% ), cough ( 24% ) and arthralgia ( 22% ).
Serious adverse effects occurred in 40% of patients; 38% of all severe adverse reactions were grade 3 or greater.
Ibrutinib works by blocking a specific protein called Bruton's tyrosine kinase ( BTK ). The BTK protein transmits important signals that tell B cells to mature and produce antibodies and is needed by specific cancer cells to multiply and spread.
Ibrutinib targets and blocks BTK, inhibiting cancer cell survival and spread. ( Xagena )
Source: Janssen, 2015