The impact of first-line therapy with novel agents in multiple myeloma patients age 80 and above: A systematic review.

Abstract

e20532 Background: Novel therapeutic agents in multiple myeloma (MM) have demonstrated significant improvements in treatment outcomes. However, data remains scarce in newly diagnosed transplant-ineligible patients aged 80 and above as they are less represented in clinical trials. Optimal treatment of this population also proves challenging due to treatment-related adverse events. Methods: MEDLINE and EMBASE search concluded March 4, 2019. We included studies that evaluated first-line treatment of age ≥80 transplant-ineligible MM patients with novel agents. The primary outcomes assessed were OS and PFS. A qualitative analysis was undertaken due to the small number of included articles. Results: Of 1683 articles assessed for eligibility, 134 articles proceeded to full-text review. 6 articles with a total of 819 patients age ≥ 80 (range 80-96) were included for analysis (5 retrospective analyses and 1 phase II, non-randomized trial). Median OS were significantly shorter in age ≥80 in comparison to younger groups (reported median OS ranged from 19.5-31.9mo for age ≥80, 46-54.8mo for age 66-79, and 81-83.8mo or not reached for age ≤65). Shorter survival was associated with poorer performance status, advanced ISS stage, higher Charlson Comorbidity Index, anemia and elevated serum LDH. In one study, attaining a very good partial response or better (≥VGPR) was associated with improved median OS (30.4mo vs 18.8mo, p = 0.001). There was no difference between age groups for OS if ≥ VGPR was attained (53.4mo in age ≥80, vs not reached in age 66-79 or age ≤65; p = 0.184). In 1 of 3 studies that reported median PFS, a significant difference in one study was noted by age [age ≥80 = 19.1mo, age 66-79 = 26.3mo (p = 0.033), ≤65 = 54.3mo (p = 0.0009)]. Early mortality (at 2 or 6 months; in 3 studies) was significantly greater than in patients age < 80 and was primarily due to infection or renal failure, and more often in the frail. One study noted that despite reduced OS, the relative survival rate was higher in patients aged ≥85 at 2 years than in younger age groups. Conclusions: Our review excluded most RCTs as subgroup analyses of patients aged ≥80 were not available. Regardless, included articles are representative of the real-world experience. This systematic review suggests that while MM patients aged ≥80 experience shorter OS and PFS, treatment with a novel agent may offer comparable survival outcomes to younger groups in those able to attain ≥VGPR. Relative survival in elderly patients also favours active treatment in this age group, while balancing the risks of early mortality.