Graham H. Jackson
Lenalidomide maintenance therapy significantly improved PFS compared with observation among patients with newly diagnosed multiple myeloma, according to a randomized, phase 3 study published in The Lancet Oncology.
The regimen, however, did not significantly improve OS in the intention-to-treat analysis of all patients in the study.
“This is a major breakthrough as it shows that the long-term use of lenalidomide significantly improves the time myeloma patients stay in remission after initial therapy,” Graham H. Jackson, MD, professor at Northern Institute for Cancer Research at Newcastle University, said in a press release. “Our research highlights that lenalidomide should be considered for newly diagnosed patients following stem cell transplantation.”
Although lenalidomide (Revlimid, Celgene) maintenance is known to improve PFS among patients with multiple myeloma, particularly following stem cell transplantation, fewer data exist on the effect of maintenance treatment among patients with cytogenic high-risk disease or who are ineligible for transplant.
Thus, Jackson and colleagues aimed to evaluate lenalidomide maintenance vs. observation aross different subgroups.
Researchers randomly assigned 1,971 adults with multiple myeloma — all of whom had at least a minimal response to induction therapy that included lenalidomide — to lenalidomide maintenance (n = 1,137) or observation (n = 834). The final protocol allocated patients in the lenalidomide group to 10 mg per day orally on days 1 to 21 of each 28-day cycle.
PFS and OS served as the primary endpoints.
Median follow-up was 31 months (interquartile range, 18-50 months)
Median PFS was 39 months (95% CI, 36-42) with lenalidomide maintenance vs. 20 months (95% CI, 18-22) with observation (HR = 0.46; 95% CI, 0.41-0.53). Lenalidomide improved PFS compared with observation across all subgroups.
Researchers reported 3-year OS of 78.6% (95% CI, 75.6-81.6) in the lenalidomide group and 75.8% (95% CI, 72.4-79.2) in the observation group (HR = 0.87; 95% CI, 0.73-1.05).
Analysis of transplant-eligible patients showed 3-year OS of 87.5% (95% CI, 84.3-90.7) with lenalidomide vs. 80.2% (95% CI, 76-84.4) with observation (HR = 0.69; 95% CI, 0.52-0.93). However, the analysis of transplant-ineligible patients did not show a significant OS benefit (3-year OS, 66.8% vs. 69.8%; HR = 1.02; 95% CI, 0.8-1.29).
Cytogenic risk subgroup analysis showed superior 3-year OS with lenalidomide vs. observation among patients with standard risk (86.4%; 95% CI, 80-90.9 vs. 81.3%; 95% CI, 74.2-86.7), high risk (74.9%; 95% CI, 65.8-81.9 vs. 63.7%; 95% CI, 52.8-72.7) and ultra-high risk (62.9%; 95% CI, 46-75.8 vs. 43.5%; 95%CI, 22.2-63.1).
However, researchers noted these data should be interpreted with caution because these subgroups were underpowered.
The most common grade 3 or grade 4 adverse events among patients assigned lenalidomide included neutropenia (33%), thrombocytopenia (7%) and anemia (4%). Serious adverse events — the most common of which were infections — occurred in 45% of patients taking lenalidomide and 17% of patients under observation.
Overall, there were 234 deaths in the lenalidomide group and 226 in the observation group. None of the deaths appeared to be because of treatment.
“Our results confirm lenalidomide can significantly prolong the lives of people living with myeloma in the largest trial to date,” Jackson said in a press release. “This treatment is not yet available on the National Health Service for this group of patients, and this represents an unmet need.”
Although lenalidomide maintenance is the standard of care for newly diagnosed multiple myeloma, future research needs to focus on a more personalized approach that will improve OS and quality of life, Maria-Victoria Mateos, MD, and Verónica González de la Calle, MD, PhD, of the hematology department at University Hospital of Salamanca, wrote n an editorial accompanying the study.
“Lenalidomide maintenance seems to be effective, well tolerated and convenient, despite the lack of OS benefit, because of the influence of rescue therapies in the OS,” the editorial authors wrote. “Lenalidomide is, therefore, a maintenance therapy option for every patient with newly diagnosed multiple myeloma, but new therapies or combinations of drugs are needed to improve overall survival in these patients.” – by John DeRosier
Disclosures: Jackson reports consultant fees, honoraria and speakers bureau fees from Amgen, Janssen, Merck Sharp and Dohme, and Roche; and consultant fees, honoraria, research funding, speakers bureau fees and travel support from Celgene and Takeda. Please see the study for all other authors’ relevant financial disclosures. Mateos reports honoraria for lectures and/or advisory board participation from AbbVie, Amgen, Celgene, GlaxoSmithKline, Janssen, PharmaMar and Takeda. De la Calle reports no relevant financial disclosures.