Background:Daratumumab (dara) with immunomodulatory agents (IMiD) and dexamethasone (dex) is highly effective in relapsed multiple myeloma (MM). The recommended schedule of dara is weekly for 8 doses, followed by 2‐weekly for 8 doses, and then every 4‐weekly thereafter. Given the high cost and the long half‐life as an antibody, a 3‐weekly dosing of dara was used together with IMiD/dexamethasone.Aims:Dara at 16 mg/kg was used every 3‐weekly with lenalidomide or pomalidomide. Patient achieving best response received single agent IMiD maintenance until disease progression.Methods:Fourteen relapsed MM patients were enrolled. One had received weekly dara from a private oncologist, hence was excluded from analysis. Thirteen patients at a median age of 63 years (range: 50–84 years) were studied. The median number of previous therapies was 2 (range: 1–5), with nine patients (69.2%) having undergone autologous stem cell transplantation. Three patients (23.1%) were refractory to bortezomib, seven patients (53.8%) to lenalidomide, and eight patients (61.5%) to last treatment. At relapse, two (15.4%) had high LDH, eight (61.5%) impaired renal function, and three (23.1%) extramedullary disease. Treatment was dara‐lenalidomide‐dex in six (46.2%), and dara‐pomalidomide‐dex in seven (53.8%).Results:Responses after four cycles included CR in 5 patients (38.5%), VGPR in five patients (38.5%), and PR in three patients (23.1%). After a median of four dara infusions (range: 3–10), the best responses included CR in seven patients (53.8%), nCR in two patients (15.4%), VGPR in two patients (15.4%), and PR in two patients (15.4%). Median time to VGPR was one month. At 10 months, the OS was 90%, and PFS 54.7%. Three patients progressed, one of whom died of ruptured hepatic plasmacytoma. The most frequent toxicity was haematological especially neutropenia (all grades: 92.3%, Grade 3/4: 76.9%), infusion reaction (38.5%, all grade 1/2), neuropathy (38.5%, all grade 1/2), gastrointestinal (all grades: 38.5%, grade 3/4 : 7.7%), and sepsis (all grades: 30.8%; grade 3/4: 23.1%). Neutropenia was effectively prevented with prophylactic G‐CSF.Summary/Conclusion:In conclusion, a 3‐weekly dara‐IMiD‐dex regimen is highly efficacious, inducing deep and rapid responses, hence cost‐effective for less affluent countries. In view of prevalent grade3/4 neutropenia despite less frequent dara, 3‐weekly dara might be more suitable for Asian patients.image