Multiple myeloma (MM) is a plasma cell malignancy that can significantly shorten the life expectancy of patients. With the use of drugs such as thalidomide, bortezomib, and lenalidomide as first-line therapy, the outcome of MM has improved significantly, but relapse still occurs, and the treatment of relapsed MM is indeed a great clinical challenge. Recently, the journal Blood discussed the treatment of relapsing MM in its How I treat series. For asymptomatic relapsing MM, treatment can be delayed appropriately; for already symptomatic, advanced relapsing MM, immediate salvage therapy is mandatory. In addition, for patients with multiple relapses, the benefits of retreatment and sequential therapy are clear. For patients with aggressive relapses and those for whom all treatment options have been used, continued treatment until disease progression is recommended. Patients in sustained remission for more than 2 years prior to first autologous stem cell transplantation (ASCT) may benefit from re-treatment with ASCT. For patients with aggressive or associated cytogenetic abnormalities with poor prognosis, allogeneic transplantation should be considered if relapse occurs in the first 2 years after ASCT. Finally, a number of new drugs are in clinical trials and some patients may be encouraged to participate in this type of study. Below, we will discuss the treatment of relapsed MM with specific cases. Case 1: Chemotherapy with VTD regimen in a patient with relapsed MM The patient, a 52-year-old female, was admitted in June 2011 with a pathological fracture and was diagnosed with IgA-λ MM (M protein 4.5 g/L and 24-hour urinary light chain protein secretion of 1163 mg). A bone marrow smear showed 57% plasma cells and no cytogenetic abnormalities. The patient then underwent hip arthroplasty and chemotherapy with a VTD regimen (bortezomib, thalidomide, dexamethasone). After 3 courses of chemotherapy, urinary light chain protein increased to 1376 mg/24 h. Salvage therapy with lenalidomide and dexamethasone was started immediately. after 4 courses, the patient achieved a good partial remission (VGPR) with urinary M protein <100 mg/24 h. The patient underwent ASCT in 2012 with pretreatment regimen of Marfalan 200 mg/m2. The patient was in VGPR until May 2013, when the disease progressed with urinary light chain protein 613 mg/24 hr. The patient had a homologous sibling donor and was scheduled for low-dose pretreatment allogeneic stem cell transplantation (Allo-RIC) after LenDex salvage therapy with lenalidomide and dexamethasone. The patient did not develop severe GVHD, and one year after Allo-RIC the patient achieved strict immunophenotypic CR and was asymptomatic. Figure 1: Primary treatment regimen and timing for this patient Point of view The patient has IgA-λ MM with light chain urine protein secretion and IgA serum levels close to the critical threshold (5 g/L). Regarding the initial treatment, we generally choose the best treatment option for both standard-risk and high-risk MM. In this patient, VTD is a highly effective induction regimen prior to ASCT. However, remission is still not achieved in 15% of patients. In this case, LenDex is the preferred salvage therapy. This patient had achieved VGPR, did not improve remission with ASCT, and had disease progression one year later, when light chain proteins were present in the patient's urine, which often indicates a poor prognosis. The patient is bortezomib resistant, has early relapse after ASCT, and is resistant to high-dose Marfalan, so Allo-RIC from a homologous sibling donor may be considered. Allogeneic stem cell transplantation (Allo-SCT) is a potentially curative therapy for advanced MM, but the clear marrow pretreatment of The prognosis of patients undergoing Allo-RIC and Allo-SCT is not significantly different. Although the transplant-related mortality (TRM) for Allo-SCT clear medullary pretreatment was over 20%, the post-transplant relapse rate was higher for Allo-RIC. Recent studies have reported a significant prolongation of PFS and OS in patients undergoing Allo-RIC. Although allogeneic transplantation remains controversial in the treatment of MM, it is recommended in two situations: 1) ASCT relapse after induction therapy; and 2) high-risk patients with poor prognostic cytogenetic abnormalities who have elevated LDH or stage III ISS staging and are resistant to all chemotherapy regimens. This patient meets the indications for Allo-SCT: aggressive disease with bone destruction and light chain protein secretion, resistance to VTD regimens, and relapse after ASCT. In this setting, current antimyeloma drugs are unlikely to result in long-term disease control. This patient did not develop severe GVHD and achieved strict CR after one year of Allo-SCT, with the promise of long-term remission and eventual cure.