LAUSR

Background Autologous hematopoietic cell transplantation (AHCT) followed by maintenance therapy is the current standard of care in the treatment of multiple myeloma (MM). Lenalidomide (Len) is most commonly utilized as maintenance therapy as it has been shown to improve both progression free survival (PFS) and overall survival (OS). However, long-term maintenance therapy with Len is associated with development of secondary primary malignancies (SPM). Proteasome-inhibitor (PI)-based maintenance strategies have been evaluated in several phase III trials and also appear to yield survival benefits in MM. Methods We performed a comprehensive search of the medical literature using PubMed/Medline and EMBASE on September 11, 2019. We extracted data on clinical outcomes related to benefits (OS, PFS and deepening of hematologic response [DOHR]) and harms (SPM), independently by two authors. Our search strategy identified total of 2144 references. Three studies (5 manuscripts) were included in this systematic review (Figure 1). Results Median age for patients receiving PI maintenance after AHCT ranged from 25 to 65 years. All patients underwent an AHCT with melphalan 200mg/m2 prior to initiation of PI maintenance. Also, 70% of patients received a PI-containing induction regimen. 513 patients received bortezomib maintenance and 395 patients received ixazomib. The control arm in these studies was either placebo (n=261) or thalidomide (n=597). PI maintenance did not improve OS (n=2 studies, 1012 patients, hazard ratio [HR] 0.88, 95% CI 0.73-0.105, p=0.15) but improved PFS (HR 0.75, 95% CI 0.67-0.85, p= Conclusions The results of our systematic review show that PI-based maintenance following AHCT in MM leads to significant improvement in PFS and DOHR without an increase in development of SPM compared to placebo/non-PI maintenance. Prospective randomized phase III trials comparing Len to PI-based maintenance is an interesting question that remains unanswered.