|The following article features coverage from the 2021 Annual Meeting of the Society of Hematologic Oncology (SOHO). Click here to read more of Cancer Therapy Advisor’s conference coverage.|
Dasatinib demonstrates efficacy in patients with chronic phase chronic myeloid leukemia (CML-CP) across all Charlson Comorbidity Index (CCI) groups, according to a post hoc analysis of the DASISION trial.1
These results suggest that comorbidities do not negatively affect the activity of tyrosine kinase inhibitors, according to a poster describing the analysis, which was presented at the Annual Meeting of the Society of Hematologic Oncology (SOHO).
In the phase 3 DASISION trial (ClinicalTrials.gov Identifier: NCT00481247) researchers compared dasatinib with imatinib in patients with newly diagnosed CML-CP. Five-year results from the trial showed faster and deeper responses with dasatinib but similar survival outcomes between the treatment arms.2
Researchers conducted an exploratory analysis to determine if comorbidities had an effect on the efficacy of dasatinib, as comorbidities are known to be common among patients with CML-CP.
Of the 519 patients enrolled in DASISION, 14 (3%) had a CCI of 2-4, 260 (50%) had a CCI of 5-6, and 245 (47%) had a CCI of 7 or greater.
The researchers noted that dasatinib improved response rates in the CCI 2-4 group, but the small patient number “precludes any clinical correlation.”
Among patients with a CCI of 5-6, dasatinib significantly improved response rates compared with imatinib. Patients treated with dasatinib had higher rates of major molecular response (MMR) — 81.1% vs 64.8% (P =.0033) — and deep molecular response (MR4.5) — 42.4% vs 29.7% (P =.0329).
Among patients with a CCI of 7 or greater, the MMR rate was numerically higher with dasatinib than with imatinib, but the difference was not statistically significant — 70.8% and 64.0%, respectively (P =.2552). The same was true for the MR4.5 rate (45.0% vs 39.2%; P =.3589).
The median time to MMR in patients with a CCI of 5-6 was significantly shorter with dasatinib than with imatinib — 15.0 months and 24.0 months, respectively (hazard ratio [HR], 1.64; 95% CI, 1.23-2.19; P =.0006).
Likewise, among patients with a CCI of 7 or greater, the median time to MMR was significantly shorter with dasatinib than with imatinib — 12.0 months and 21.4 months, respectively (HR, 1.41; 95% CI, 1.04-1.91; P =.0279).
Rates of grade 3/4 treatment-related adverse events (TRAEs) — in the dasatinib and imatinib arms, respectively — were 0% and 14% in the CCI 2-4 group, 8% and 9% in the CCI 5-6 group, and 24% and 13% in patients with a CCI of 7 or greater.
There were no grade 3/4 TRAEs leading to discontinuation in the CCI 2-4 group. For the other CCI groups, rates of grade 3/4 TRAEs leading to discontinuation were similar between the treatment arms.
Patients treated with dasatinib had higher rates of pleural effusion than did patients who received imatinib in both the CCI 5-6 group (18.2% vs 0.8%) and in patients with a CCI of 7 or greater (41.2% vs 0.8%).
“From both a safety and efficacy perspective, these findings support the use of dasatinib as first-line treatment in patients with CML-CP and substantial comorbidity burden,” the researchers concluded.
Disclosures: This research was supported by Bristol Myers Squibb. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Read more of Cancer Therapy Advisor’s coverage of SOHO 2021 by visiting the conference page.
1. Breccia M, Mauro M, Jabbour E, et al. Effects of comorbidities on response outcomes with first-line tyrosine kinase inhibitors, dasatinib versus imatinib, in patients with chronic myeloid leukemia in chronic phase: Exploratory post hoc analysis of DASISION. Paper presented at: Annual Meeting of the Society of Hematologic Oncology (SOHO); September 8-11, 2021.
2. Cortes JE, Saglio G, Kantarjian HM, et al. Final 5-year study results of DASISION: The dasatinib versus imatinib study in treatment-naïve chronic myeloid leukemia patients trial. J Clin Oncol. 2016;34(20):2333-40. doi:10.1200/JCO.2015.64.8899