A 46-year-old man presents with a pathological fracture of his left clavicle. He is diagnosed as suffering from plasma cell myeloma (PCM) based on a skeletal survey indicating multiple lytic lesions, serum electrophoresis revealing an immunoglobulin G (IgG) κ level of 54 g/l and a bone marrow infiltrate of 24% malignant plasma cells on diagnostic biopsy. He has one human leukocyte antigen (HLA)-identical sibling.
What is the optimal management of the man's disease?
What is the role of allogeneic stem cell transplantation in his management strategy?
Where in his management should novel therapy be introduced?
Prior to the introduction of alkylating agents, the median survival of patients with PCM was less than 1 year.1 Approximately 60% of patients will respond to conventional chemotherapy, though approximately 25% of patients will be alive at 5 years and less than 10% will be alive at 10 years. The aim of therapy in patients with PCM is to control the disease process, to maximize quality of life and to prolong survival. Response criteria were first developed by the Committee of the Chronic Leukemia and Myeloma Task Force of the US National Cancer Institute in 1968, and were subsequently reviewed in 1973. In 1998, the Myeloma Subcommittee of the European Blood and Marrow Transplantation (EBMT) Chronic Leukaemia Working Party, in collaboration with the Myeloma Working Committee of the International Bone Marrow Transplant Registry, set out what have been universally adopted response criteria.2 The main tenets are illustrated in Table 34.1. The published documents provide criteria for complete response (CR), partial response (PR), minimal response, stable disease, progressive disease, plateau response and relapse.
Table 34.1EBMT clinical response criteria.2 |Favorite Table|Download (.pdf) Table 34.1 EBMT clinical response criteria.2
|Complete response (CR) requires all of the following: |
|1. Absence of the original monoclonal paraprotein in serum and urine by immunofixation, maintained for a minimum of 6 weeks. The presence of oligoclonal bands consistent with oligoclonal immune reconstitution does not exclude CR. |
|2. <5% plasma cells in a bone marrow aspirate and also on trephine bone biopsy if biopsy is performed. If absence of monoclonal protein is sustained for 6 weeks it is not necessary to repeat the bone marrow examination, except in patients with non-secretory myeloma where the marrow examination must be repeated after an interval of at least 6 weeks to confirm CR. |
|3. No increase in size or number of lytic bone lesions (development of a compression fracture does not exclude response). |
|4. Disappearance of soft tissue plasmacytomas. |
|Patients in whom some, but not all, of the criteria for CR are fulfilled are classified as PR, providing the remaining criteria satisfy the requirements for PR. This includes patients in whom routine electrophoresis is negative but in whom immunofixation has not been performed. |
|Partial response (PR) requires all of the following: |
|1. ≥50% reduction in the level of the serum monoclonal paraprotein, maintained for a minimum of 6 weeks. |
|2. Reduction in 24-hour urinary light chain excretion either by ≥90% or to <200 mg, maintained for a minimum of 6 weeks. |
|3. For patients with non-secretory myeloma only, ≥50% reduction in plasma cells in a bone marrow aspirate and on trephine biopsy, if biopsy is performed, maintained for a minimum of 6 weeks. |