Ibrutinib May Be Effective in Patients With Chronic Lymphocytic Leukemia Who Were Excluded from Clinical Trials
The RESONATE-2 trial excluded certain patients with chronic lymphocytic leukemia, leaving the efficacy and tolerability of ibrutinib in this population unknown.
Ibrutinib monotherapy may improve treatment outcomes among patients with chronic lymphocytic leukemia (CLL) who are younger than 65 years or who have a chromosome 17p13 deletion (del(17p13)), according to findings published in the American Journal of Hematology.1
The phase 3 RESONATE-2 trial (ClinicalTrials.gov Identifier: NCT01722487) was a landmark study leading to US Food and Drug Administration approval of ibrutinib in the frontline setting for CLL. RESONATE-2 excluded patients younger than 65 years and/or those who had the chromosomal deletion del(17p13). This exclusion limited the information about ibrutinib efficacy and tolerability across all patients with CLL..
For this retrospective study, researchers analyzed 391 potential patients with CLL who received ibrutinib 420 mg as a first-line therapy. Patients were categorized according to original RESONATE-2 criteria. Of the 391 patients identified, 41% (160) and 30% (110) were younger than 65 years and had del(17p13), respectively; translating into 57% of the study patients who would have been excluded from the original RESONATE-2 study based on the trial's key inclusion criteria.
Results showed that younger patients were significantly more likely to initiate therapy at the median starting dose of ibrutinib 420 mg (11.3% vs 2.5%; P = .01), and less likely to have dose reductions prior to maintaining a stable dose (19.9% vs 13.1%; P = .01). Starting on a lower dose was associated with inferior 12-month progression-free survival (PFS) (71% vs 93%; hazard ratio [HR], 3.3; 95% CI, 1.5-7.0; P = .003). There were no differences in the starting dose between patients with or without del(17p13).
Younger patients and those with del(17p13) had similar response rates, but patients characterized by del(17p13) had poorer PFS and overall survival.
The most frequently reported toxicities observed in patients included arthralgia, fatigue, rash, bruising, and diarrhea. Treatment-related adverse events were the most common cause for treatment discontinuation during follow-up (24% of patients), but progression and/or transformation were responsible for a larger proportion of discontinuations among those who were both younger than 65 years and had del(17p13).
The authors concluded that “as novel agents are increasingly used to manage CLL, insight into outcomes and toxicities for groups lacking robust clinical trial data will allow for more informed decision-making as we optimize our approach to [the disease].”
- Mato AR, Roeker LE, Allan JN, et al. Outcomes of front0line ibrutinib treated CLL patients excluded from landmark clinical trial[published online August 21, 2018]. Am J Hematol. doi: 10.1002/ajh.25261