Hollywood, FL—In a study presented at the 2016 annual conference of the National Comprehensive Cancer Network, a real-world assessment of lenalidomide use in the treatment of patients with myelodysplastic syndrome (MDS) showed that dose modifications had a strong positive effect on outcomes.
Amy E. DeZern, MD, MHS, of the Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, presented an analysis of the MarketScan Commercial Claims and Medicare Supplemental Database from 2013. Results showed that in the treatment of MDS, dose modifications allow patients to continue using lenalidomide beyond 3 cycles, and to reap the multiple benefits associated with sustained therapy.
“Dose modification of lenalidomide has been commonly used by physicians to sustain control of disease while managing toxicities,” Dr DeZern noted. “Real-world assessments of lenalidomide usage and dosing in MDS treatment can help physicians gain better insight into the effects of dose modification on patient outcomes and safety, as well as potentially elucidate the effect of dose modification compared with discontinuation of lenalidomide therapy.”
The retrospective analysis focused on 529 patients with MDS treated with lenalidomide as first-line therapy, without stem-cell transplantation. Median duration of treatment and time to disease progression were compared between patients with (46%) and without (54%) dose modifications. The median time to dose modification was 1.9 months. Age and comorbidities did not differ between patients by dose modifications. Most patients started with lenalidomide 10 mg daily. The most common modification was to reduce the dose to 5 mg daily. The reasons for dose modification or discontinuation of treatment were unknown.
Positive Impact of Dose Modification
Median duration of treatment was 12.6 months for patients with dose modifications compared with 1.9 months for those without, with an adjusted hazard ratio of 0.221 (P <.0001), Dr DeZern reported. In addition, for the overall population the median time to progression was 20.6 months for patients with a dose modification, versus 13.7 months for those without, with an adjusted hazard ratio of 0.703 (P = .009). Significant improvements in time to development of acute myeloid leukemia (P = .018), time to next treatment (P = .002), and time to high-risk disease (P = .043) were also improved for patients with dose modifications.
In a subgroup analysis of patients receiving <4 versus ≥4 cycles of lenalidomide, median duration of treatment was 3.0 months for patients with dose modifications compared with 1.7 months for those without (P <.0001); for patients receiving ≥4 cycles, the duration of treatment was 16.5 months and 10.8 months, respectively (P = .007). The median time to progression was approximately 8 months for all patients (regardless of dose modification) among those who received <4 cycles, and almost 24 months when patients received ≥4 cycles.
The researchers acknowledged that this retrospective study is subject to the usual limitations of such studies, and that some data relevant to the topic were incomplete. Nevertheless, they believe the data are reassuring for physicians who feel the need to reduce doses.
“Although the decision to use dose modification versus discontinuation can be challenging, these data suggest that quality of care for MDS patients can be maintained through lenalidomide dose modification as a strategy to sustain therapy beyond 3 cycles and achieve the time to progression benefits associated with continued treatment,” Dr DeZern concluded.