Abstract:80 patients with resistant or relapsing multiple myeloma received a combination of vincristine, cyclophosphamide, lomustine, melphalan and methylprednisolone (MOCCA) as a second‐line chemotherapy. 27 of them were resistant to primary chemotherapy with alkylating agents, and 53 had relapsed after initially responding to these drugs. An objective response was achieved in 39 patients (49%): in 14 patients who were primarily resistant (52%) and in 25 patients who had a relapse (47%). Of 41 patients relapsing during maintenance chemotherapy 14 (34%) responded, while 11 of 12 patients (92%) treated for a relapse off‐therapy responded. The median duration of response was 22 months. Severe complications, in most cases infections, occurred in 30% of patients, and were fatal in 9% of the cases. According to our experience the five‐drug combination MOCCA is an effective second‐line chemotherapy for myeloma patients primarily resistant to or relapsing after therapy with single alkylating