OBJECTIVES:  To compare overall survival (OS) for daratumumab monotherapy with pomalidomide plus low dose dexamethasone (POMA+LoDex) in heavily pre-treated multiple myeloma (MM) patients, using the matching adjusted indirect comparison (MAIC) technique. METHODS:  In the absence of trials of daratumumab and POMA+LoDex with a common comparator, a MAIC between both treatments was conducted. MAIC attempts to make trial populations comparable through reweighting of the patient level daratumumab trial data to mimic the population of another trial for which only aggregate data are available. Individual patient data from the pooled daratumumab studies (patients treated with 16 mg/kg in GEN501/MMY2002) (Usmani. Blood 2016) and aggregate results from of the POMA+LoDex study (MM003) (San Miguel. Lancet Oncology 2013;14(11). Dimopoulos. Haematologica 2015;100(10)) were utilised. The method matched the inclusion/exclusion criteria and baseline characteristics (refractoriness to lenalidomide/bortezomib, number of prior regimens, creatinine clearance, ECOG status, time since diagnosis, myeloma subtype, race, bone lesions, prior autologus stem cell transplant, age) across the trials. As the MM003 trial only included POMA-naïve patients, POMA-experienced patients were additionally excluded from the daratumumab dataset in a sensitivity analysis in order to make trial populations more comparable. RESULTS:  148 patients received daratumumab 16mg/kg in GEN501/MMY2002 combined. After MAIC-adjustment, all available baseline characteristics were well balanced across the trial populations. The MAIC-adjusted hazard ratio (HR) for OS was 0.56 (95% CI 0.38; 0.83) when all available baseline characteristics were matched. When patients with prior POMA exposure were excluded from the daratumumab dataset, the OS HR was even more favourable to daratumumab, 0.33 (95% CI 0.17; 0.66). CONCLUSIONS:  In the absence of head-to-head trials, indirect comparisons can provide useful insights to clinicians and reimbursement authorities around the relative efficacy of treatments. The MAIC results suggest that daratumumab improves overall survival compared to POMA+LoDex in patients with heavily pre-treated MM.