Background: Pomalidomide-based regimens are the cornerstone of treatment for relapsed/refractory MM (RRMM). Despite the high incidence of chronic kidney disease (CKD) in RRMM, individuals with advanced CKD have been excluded from phase II/III RCTs, creating a gap in our understanding of the effects of pomalidomide use in patients with RRMM complicated with advanced CKD. We undertook a cohort to study to understand the efficacy safety of pomalidomide-based regimens among patients with CKD using real-world data. Methods: Population-based, cohort study of patients ≥ 18 years with RRMM treated with pomalidomide in Ontario, Canada. Primary outcome was all-cause mortality. Secondary outcomes were time-to-major adverse kidney events (MAKE), time-to-next treatment, kidney response and safety. Results: 748 patients with RRMM utilizing pomalidomide were included; 440 had preserved kidney function, 210 had moderate CKD (eGFR 30-59 ml/min/1.73m2), and 98 had advanced CKD (eGFR <30 ml/min/1.73m2). Mean age was 70.2 years, 43.3% were women. Patients with advanced CKD had a higher risk of all-cause mortality compared to the preserved kidney function group (aHR 1.37, 95% CI 1.06, 1.78). MAKE was higher in advanced CKD (aHR 1.70, 95% CI 1.03, 2.35). Kidney response was similar between moderate and severe CKD groups (aOR 1.04, 95%, CI 0.56-1.90). Safety outcomes were similar between groups. Conclusions: Patients with advanced CKD and RRMM on pomalidomide-based regimens exhibited reduced survival and a higher risk for MAKE. However, the probability of experiencing some degree of kidney recovery is 50% in both moderate and severe CKD, with comparable safety outcomes. Micro-abstractOur study aims to fill a gap created by excluding patients with multiple myeloma (MM) and advanced chronic kidney disease (CKD) from RCTs. We utilized administrative data available in Ontario, Canada and included patients with moderate/advanced CKD and RRMM, treated with pomalidomide-based regimens. Compared with patients with preserved renal function, pomalidomide is safe in patients with moderate/advanced CKD, and both groups demonstrated 50% likelihood of renal recovery. Mortality is increased in the advanced CKD group, mainly driven by patients on renal replacement therapy. Clinical Practice pointsPatients with relapsed/refractory MM (RRMM) are at increased risk of CKD and at the CKD is also a risk factor for adverse outcomes in MM including mortality. Despite the higher incidence and prevalence of CKD in MM, patients with advanced CKD have been excluded from randomized controlled trials evaluating novel MM therapies, including pomalidomideTo fill this gap in our knowledge, we undertook a population-based, retrospective, cohort study of individuals ≥ 18 years with RRMM treated with pomalidomide in Ontario, Canada. The primary outcome was all-cause mortality. Secondary outcomes were kidney response, time-to-major adverse kidney events (MAKE), time-to-next treatment, and safety events.We found that patients with advanced CKD had a higher risk of all-cause mortality compared to the preserved kidney function group, driven by patients on hemodialysis. Kidney response rates were similar in both moderate and severe CKD groups, around 50%. MAKE were more frequent in advanced CKD. Safety outcomes were similar in patients with normal renal function and those with CKD.Our findings confirm that pomalidomide is safe to use in patients with moderate to severe CKD. Moreover, patients with both moderate and advanced CKD may recover kidney function. Therefore, pomalidomide-base regimens can be used in patients with CKD and these patient should not be precluded from treatment.