META-ANALYSIS AND INDIRECT TREATMENT COMPARISON OF SAFETY PROFILES OF BORTEZOMIB- AND THALIDOMIDE-BASED REGIMENS FOR THE FIRST LINE TREATMENT OF ELDERLY TRANSPLANT-INELIGIBLE PATIENTS WITH MULTIPLE MYELOMA
Method(s): A systematic literature review was conducted and eligible studies (randomized clinical trials (RCT) comparing first-line therapies for MM) were identified from several databases including Medline, Embase, Cochrane Library and CRD. We extracted data on grade 3-4 adverse events and calculated pooled odds ratios (OR) with 95% confidence intervals (CI). A random-effects meta-analysis and indirect treatment comparison were performed to compare treatment-related adverse events (AEs) in the included clinical trials.
Result(s): Our meta-analysis included six studies comparing MP and MPT with a total of 1399 patients. Withdrawals due to AEs were significantly lower in MP treatment when compared with MPT 0.18 (0.12-0.28) (OR (95% CI)). The MP regimen was associated with a significantly lower risk of DVT 0.37 (0.15-0.86), as well as a decreased risk of constipation 0.45 (0.27-0.77), infection 0.46 (0.30- 0.71) and peripheral neuropathy 0.25 (0.09-0.67). Other AEs including neutropenia, cardiac disorder, rash and nausea were less frequent for MP but the differences were not statistically significant. The indirect treatment comparison assessed the safety of MPV compared with MPT and CTd with MPT using MP as common comparator. Results of indirect comparisons did not show statistically significant difference except in the case of peripheral neuropathy 0.04 (0.00-0.90) and nausea 0.11 (0.03-0.48), which were less frequent in MPV regimen.
Conclusion(s): Based on the results of our comparative safety analysis, the MP regimen appears to have a favorable safety profile. The addition of novel and more potent therapeutic agents is in general followed by an increase of grade 3 and 4 adverse events. Therefore, the benefits and harms of the treatment alternatives should be carefully balanced, particularly in elderly patients, although higher and deeper responses, a better progression-free survival (PFS) as well as overall survival (OS) has been reported for triplet therapies comprising novel agents in multiple clinical trials.