Bortezomib and lenalidomide as front-line therapy for multiple myeloma

Abstract

The objective of the study was to investigate the effects and safety of novel agents such as bortezomib and lenalidomide in the treatment of newly diagnosed patients with multiple myeloma. We performed a comprehensive meta-analysis of randomized controlled trials (RCTs). An initial search yielded 627 citations, of which 10 RCTs enrolling 4534 patients met the inclusion criteria. The addition of bortezomib to first-line therapy significantly prolonged overall survival (OS) (hazard ratio [HR], 0.75 [0.65, 0.87], p < 0.001). On the other hand, the addition of lenalidomide had no impact on survival (HR, 0.88 [0.65, 1.20], p = 0.42). Both lenalidomide and bortezomib consistently improved progression-free survival (PFS) compared with conventional therapy alone. The corresponding HRs were 0.65, 95% confidence interval (CI) [0.55, 0.77] (p < 0.001) for bortezomib and 0.48, 95% CI [0.42, 0.55]; (p < 0.001) for lenalidomide, respectively. Some of the increased adverse events reported were herpes zoster (relative risk [RR], 3.64 [2.23, 5.94], p < 0.001), peripheral neuropathy (RR, 3.59 [1.89, 6.83], p < 0.001) and gastrointestinal effects (RR, 2.19 [1.37, 3.50], p = 0.001) among patients receiving bortezomib, and gastrointestinal effects (RR, 2.36 [1.33, 4.17], p = 0.003) and thromboembolic events (RR, 2.55 [1.48, 4.38], p < 0.001) among patients receiving lenalidomide. Interestingly, treatment with bortezomib seemed to be associated with a lower rate of treatment related mortality (RR, 0.39 [0.18, 0.85], p = 0.02). An increased incidence of second primary cancers was observed in the lenalidomide group (RR 2.61 [1.60, 4.27], p < 0.001). In summary, bortezomib improved OS, and both lenalidomide and bortezomib consistently improved PFS of patients with newly diagnosed myeloma when it was added to standard therapy.

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

“…The findings from Yang et al [ 37 ] indicated that lenalidomide therapy significantly improved response rates and increased PFS in patients with newly diagnosed MM and in those who received previous antimyeloma therapy. Study from Zou et al [ 38 ] suggested that there was a statistically significant difference for the outcome of PFS and OS favoring bortezomib arms versus controls. In addition, there was a statistically significant difference with lenalidomide arms versus controls for PFS but not OS.…”

Looking back to move forward: a twenty-year audit of herpes zoster in Asia-Pacific

“…The principal predisposing factors are iatrogenic or pathologic immunosuppression (Fig. 6) [137, 157–167]. Inpatients with severe illnesses or recovering from surgery develop HZ more frequently than others [168].…”

“…Adjusted for age and other confounding variables, several comorbidities have been identified as independent risk factors for HZ, most notably renal disease, malignancies, and SLE (Fig. 6) [137, 157–167]. …”

The Applicability of the International Staging System in Chinese Patients with Multiple Myeloma Receiving Bortezomib or Thalidomide-Based Regimens as Induction Therapy: A Multicenter Analysis

“…From previous studies we can indicate that MM patients can achieve deeper response by the use of novel agents, improved PFS and OS [ 13 ]. A meta-analysis performed by Zou et al showed the addition of bortezomib to first-line therapy did significantly prolong OS compared with conventional therapy alone [ 14 ]. Some studies have showed that bortezomib-based regimens can improve outcome of patients with t(4;14), deletion of chromosome 13, and deletion of 17p, respectively [ 15 – 17 ].…”