Chemotherapy Plus Lenalidomide Inferior to Standard for Myeloma

November 30, 2015

Chemotherapy plus lenalidomide was shown to be inferior to high-dose melphalan and ASCT in transplant-eligible patients with newly diagnosed multiple myeloma.

The use of high-dose melphalan and autologous stem cell transplantation (ASCT) resulted in improved progression-free and overall survival in transplant-eligible patients with newly diagnosed multiple myeloma compared with treatment with chemotherapy plus lenalidomide, according to the results of a study published in Lancet Oncology.

In addition, maintenance therapy with lenalidomide plus prednisone did not improve survival compared with treatment with lenalidomide alone.

“Our results confirm that consolidation with high-dose melphalan and ASCT remains the preferred therapeutic option in transplant-eligible patients with newly diagnosed multiple myeloma,” wrote Francesca Gay, MD, of the University of Torino, Italy, and colleagues. “This regimen improves progression-free survival and overall survival at a cost of increased but manageable adverse events.”

The study was conducted at 59 centers and included 389 patients with newly diagnosed myeloma who were transplant eligible. All patients received induction therapy with four 28-day cycles of lenalidomide and dexamethasone and subsequent chemotherapy with cyclophosphamide followed by granulocyte colony-stimulating factor. The patients were then randomly assigned to consolidation with either:

♦ Chemotherapy plus lenalidomide (6 cycles of cyclophosphamide [300 mg/m2, days 1, 8, and 15], dexamethasone [40 mg, days 1, 8, 15, and 22], and lenalidomide [25 mg, days 1–21]) (n = 129), or

♦ Two courses of high-dose melphalan (200 mg/m2) and ASCT (n = 127).

Eligible patients were then also randomly assigned to maintenance therapy with lenalidomide plus prednisone (n = 117) or lenalidomide alone (n = 106). The primary endpoint of the study was progression-free survival.

After a median follow-up of 52 months, results showed that consolidation with chemotherapy plus lenalidomide resulted in a significantly shorter progression-free survival compared with high-dose melphalan and ASCT (28.6 vs 43.3 months; P < .0001).

No significant difference in progression was noted for patients in the two maintenance groups, with a median progression-free survival of 37.5 months for patients assigned lenalidomide plus prednisone compared with 28.5 months for lenalidomide alone.

“Subgroup analyses of progression-free survival and overall survival confirmed the inferiority of chemotherapy plus lenalidomide versus high-dose melphalan and ASCT in most subgroups analyzed, including the lenalidomide plus prednisone and lenalidomide populations,” the researchers wrote.

However, a post-hoc analysis did show that patients with standard-risk chromosomal abnormalities assigned to chemotherapy plus lenalidomide had a better progression-free and overall survival than did patients with high-risk chromosomal abnormalities. This difference was less evident in patients assigned melphalan and ASCT.

“Unfortunately, the low number of patients in each subgroup, plus the number of patients not evaluable for cytogenetic risk, limited the value of this analysis,” the researchers wrote.

In a comparison of adverse events between the treatment arms, the researchers found that fewer grade 3 or 4 events occurred in patients assigned chemotherapy plus lenalidomide. During the maintenance phase of treatment, no significant difference in the occurrence of adverse events was found between the treatment groups.

“Despite the increase in hematological and non-hematological adverse events with high-dose melphalan and ASCT, toxic effects were manageable and did not increase the incidence of early death or treatment discontinuation,” the researchers concluded.