Less Neuropathy Seen With Lenalidomide Regimen for Myeloma

Despite similar survival outcomes, patients with newly diagnosed multiple myeloma treated with lenalidomide, melphalan, and prednisone with lenalidomide maintenance (MPR-R) experienced lower rates of neurologic toxicity compared with patients treated with a standard regimen of thalidomide, melphalan, and prednisone with thalidomide maintenance (MPT-T), according to the results of the Dutch-Belgium Cooperative Trial Group for Hematology Oncology Group (HOVON) 87/Nordic Myeloma Study Group (NMSG) 18 trial. The results were published in Blood.

“Because of similar efficacy of both regimens, but a pronounced difference in neuropathy, in our opinion MPR-R is the preferred regimen over MPT-T,” wrote Sonja Zweegman, MD, PhD, of VU University Medical Center in Amsterdam, and colleagues. “However, on a global perspective, taking accessibility and costs of novel agents and the required growth factors using MPR-R into account, a role for MPT-T, especially in good risk patients remains, provided that close monitoring of the development of neuropathy and early discontinuation of thalidomide is secured.”

Previous research has shown that long-term treatment with thalidomide is associated with significant neurotoxicity. In this study, Zweegman and colleagues explored whether use of lenalidomide in place of thalidomide could improve outcomes in older patients with newly diagnosed myeloma.

In the study, 668 patients age 65 years or older with newly diagnosed multiple myeloma ineligible for transplant were randomly assigned to nine 4-weekly cycles of MPT-T (n = 318) or to the same regimen with lenalidomide (MPR-R; n = 319).

Patients assigned to both regimens had a similar median progression-free survival (lenalidomide, 23 months vs thalidomide, 20 months). The researchers looked at the data stratified by patient age and found no significant difference in progression-free survival.

With a follow-up of 36 months, the overall survival for patients assigned MPT-T compared with MPR-R was 73% vs 84% at 2 years, 64% vs 69% at 3 years, and 52% vs 56% at 4 years.

Patients assigned to MPT-T had significantly worse grade 3 or higher neuropathy compared with patients assigned to MPR-R (16% vs 2%), which the researchers said resulted in a significantly shorter duration of maintenance therapy (5 vs 17 months).

“The significantly higher incidence of grade 3 and 4 neuropathy was the main reason for the high discontinuation rate of nearly 70% during thalidomide maintenance, with a median duration of therapy of only 5 months,” the researchers wrote. “In contrast, lenalidomide maintenance was feasible, irrespective of age, supported by a similar duration of maintenance treatment of 17 and 15 months in patients ≤ 75 and > 75 years, respectively.”

Grade 3/4 hematologic toxicities were significantly higher in patients assigned MPR-R compared with MPT-T, including occurrence of anemia, thrombocytopenia, and neutropenia; 38% of patients assigned MPR-R were prescribed granulocyte-macrophage colony-stimulating factor compared with 16% of patients assigned MPT-T (P < .001).

“In conclusion, MPR-R has no advantage over MPT-T with respect to response rate, progression-free survival, and overall survival. However, the use of thalidomide as maintenance therapy was associated with a high rate of clinically significant neuropathy and is therefore not preferred for maintenance strategies. In contrast, the hematologic toxicity profile of MPR-R did require growth factor support, but did not translate in a higher clinical infection rate, and therefore is manageable, also in patients over 75 years of age,” the researchers wrote.