Lenalidomide Induction and Maintenance Therapy for Transplant-Eligible Myeloma Patients: Results of the Myeloma XI Study
Immunomodulatory drugs (IMiDs) are effective therapies for multiple myeloma (MM), with lenalidomide having fewer side effects than thalidomide, which enables treatment for longer periods of time. The optimal IMiD induction and maintenance regimen is yet to be established for patients with MM. Myeloma XI is a multicenter, randomized, controlled trial that compared triplet induction regimens of lenalidomide versus thalidomide and examined the role of lenalidomide for maintenance therapy versus traditional observation. These regimens were tested in patients with newly diagnosed MM, with separate treatment pathways for transplant-eligible (TE) and non-TE patients.
The primary end points that were tested in the Myeloma XI Study were overall survival (OS) and progression-free survival (PFS); secondary end points tested included tumor response and toxicity. In patients who are TE, investigators compared lenalidomide, cyclophosphamide, and dexamethasone (CRD) versus thalidomide plus cyclophosphamide and dexamethasone (CTD) for a minimum of 4 cycles and up to maximum response. Patients who exhibited a suboptimal response were randomized to receive either a proteasome inhibitor–containing triplet or no further therapy prior to autologous stem-cell transplant (ASCT). To analyze the agents for maintenance therapy, randomization took place at 3 months post-ASCT and compared lenalidomide until disease progression versus observation. A total of 2042 TE patients underwent induction randomization. After a median follow-up of approximately 36 months, CRD was associated with significantly longer PFS than CTD (P = 0.0124), as well as significantly longer OS (P = 0.0083). In maintenance therapy, lenalidomide was associated with a significantly longer median PFS compared with observation (P <0.0001) across all subgroups, including patients with high-risk disease.
Tumor responses were deeper with CRD than with CTD, with a PFS and OS benefit. The best outcomes were associated with lenalidomide induction plus lenalidomide maintenance therapy. These study findings support continuing lenalidomide therapy through induction until disease progression.
Jackson GH, et al. ASCO Abstract 8009.