Efficacy and Safety of Novel Agent-Based Therapies for Multiple Myeloma: A Meta-Analysis

Abstract

This study aimed at comparing bortezomib, thalidomide, and lenalidomide in patients with multiple myeloma (MM) for safety and efficacy using meta-analysis. This meta-analysis identified 17 randomized controlled trials (RCTs) including 6742 patients. These RCTs were separated according to the different agent-based regimens and to autologous stem-cell transplantation (ASCT). Complete response (CR), progression-free survival (PFS), overall survival (OS), and adverse events (AE) were combined. The total weighted risk ratio (RR) of CR was 3.29 [95% confidence interval (95% CI): 2.22–4.88] (P < 0.0001) for the novel agent-based regimens. These novel agent-based regimens showed greater benefit in terms of PFS of all subgroups irrespective of whether the patient received ASCT or not. The hazard ratio (HR) for PFS was 0.64 [95% CI: 0.60–0.69] (P < 0.00001). Improvements of OS could be found only in the bortezomib- and thalidomide-based regimens without ASCT. The pooled HRs were 0.74 [95% CI: 0.65–0.86] (P < 0.0001) and 0.80 [95% CI: 0.70–0.90] (P = 0.0004), respectively. Several AEs were shown more frequently in the novel agent-based regimens compared with controls such as hematologic events (neutropenia, anemia, and thrombocytopenia), gastrointestinal infection, peripheral neuropathy, thrombosis, and embolism events. In conclusion, in spite of the AEs, novel agent-based regimens are safe and effective for the treatment of MM.

Treatment evolution and improved survival in multiple myeloma in Taiwan

“…Since 2007, the first-line treatment of MM has changed dramatically; almost all patients (89.4%) received novel agents alone or combined with chemotherapy in 2015, and the rate of transplantation almost doubled. Over the same period, OS increased and while our study was not designed to show a causal association between treatment use and survival, the increase in OS is consistent with clinical benefit, including increased survival, associated with the use of novel agents and transplantation as demonstrated in clinical trials and epidemiological studies [11,12].…”

Bacterial Pneumonia in Patients with Cancer

“…For example, alkylating agents also cause immune dysfunction through disproportionate depletion of CD4 + T cells, relative to CD8 + T cells [78-80]. Tyrosine kinase inhibitors increase risks for bacterial pneumonia through both neutropenia-dependent and -independent mechanisms, possibly including effects on antibody class switching [81, 82]. Anthracyclines, taxanes, topoisomerase inhibitors, and vinca alkaloids all appear capable of increasing risk of bacterial pneumonia via non-neutropenic mechanisms during treatment [83].…”

Multiple myeloma presenting with bilateral ankle pain (microangiopathy) and complicated by streptococcal meningitis andPneumocystis cariniipneumonia

“…Using meta-analysis, Wang X compared novel-based regimens using bortezomib, thalidomide and lenalidomide in patients with myeloma for safety and efficacy. This study showed greater benefit in terms of progression-free survival of all subgroups, irrespective of whether the patient received autologous stem-cell transplantation 6. However, compared to the control group, a higher proportion of adverse events including neutropenia, thrombocytopenia, peripheral neuropathy and thrombosis occurred in the novel agent groups 6…”

“…PET/CT is indeed a valuable imaging tool for the assessment of extra-medullary involvement. Regelink's systematic review supports the International Myeloma Working Group guidelines, which recommend that whole body CT can replace whole body X-ray 6. However, additional radiographs of the skull and ribs are advised as they are often underdiagnosed by modern imaging 7.…”