Lenalidomide versus thalidomide based regimens as first-line therapy for patients with multiple myeloma

Abstract

Thalidomide (T) and lenalidomide (R) have been used as first-line therapy for previously untreated myeloma. However, direct head-to-head comparison between them is lacking. We performed an indirect meta-analysis to assess the treatment effects of lenalidomide- versus thalidomide-based regimens using common comparators. A comprehensive literature search was undertaken. The initial search yielded 1345 citations, of which 11 randomized controlled trials (RCTs) enrolling 4162 patients met the inclusion criteria. Indirect comparison of lenalidomide versus thalidomide maintenance after autologous stem cell transplant (ASCT) showed a progression-free survival (PFS) benefit (hazard ratio [HR] 0.75, 95% confidence interval [CI] [0.67, 0.85], p < 0.001) but no survival difference (HR 0.83, [0.63, 1.09], p = 0.19) when using observation/placebo as the common comparator. Similarly, the indirect comparison of melphalan-prednisone plus lenalidomide followed by lenalidomide maintenance (MPR-R) versus melphalan-prednisone-thalidomide induction followed by thalidomide maintenance (MPT-T) showed a statistically significant PFS advantage for MPR-R (HR 0.53, 95% CI [0.46, 0.60], p < 0.001), but no difference for overall survival (OS) (HR 0.97, [0.81, 1.17], p = 0.74). Additionally, the significant heterogeneity among pooled studies for the outcome of discontinuation rate due to treatment-related adverse events between MPT-T and MPR-R subgroups (p = 0.007) indicated that the discontinuation rate from thalidomide trials seems to be higher than that from lenalidomide trials. In conclusion, lenalidomide seems to be a more potent and less toxic agent than thalidomide in the treatment of patients with multiple myeloma. Further, a direct head-to-head trial comparing lenalidomide versus thalidomide is clearly warranted.

A systematic literature review and network meta-analysis of treatments for patients with untreated multiple myeloma not eligible for stem cell transplantation

“…Data also indicated that the discontinuation rate from thalidomide trials appeared higher than in lenalidomide trials, suggesting that lenalidomide is less toxic than thalidomide. [39] Compared with MPT, one indirect comparison analysis showed that VMP statistically significantly prolonged both PFS and OS (p < 0.001 in each case). However, the OS benefit in the VMP group did not apply to elderly patients (75 years).…”

Poor Safety and Tolerability Hamper Reaching a Potentially Therapeutic Dose in the Use of Thalidomide for Alzheimer’s Disease: Results from a Double-Blind, Placebo-Controlled Trial

“…When compared to other compounds, cancer patients preferred to drop out of treatment than continuing with thalidomide [23]. A long list of adverse events, most of which were observed in the present study, has been drawn over the past decades [18].…”

A novel effect of thalidomide and its analogs: suppression of cereblon ubiquitination enhances ubiquitin ligase function

“…Interestingly, we noticed that lenalidomide has a greater inhibitory effect on CRBN ubiquitination and results in increased CRBN levels in cells than thalidomide. Lenalidomide appears to more clinically effective at a concentration much lower than that of thalidomide (35). Conceivably, the higher efficacy of lenalidomide reflects its improved ability to enhance CRBN accumulation, especially in cells that show low CRBN levels.…”