Utility of the Bone-marrow Exam for Complete Remission in Myeloma
Utility of the Bone-marrow Exam for Complete Remission in Myeloma
Abstract & Commentary
By Andrew S. Artz, MD, Division of Hematology/Oncology, University of Chicago. Dr. Artz reports no financial relationships relevant to this field of study.
Synopsis: Formal criteria for a complete response (CR) in multiple myeloma (MM) require a bone-marrow (BM) examination showing < 5% plasma cells. It remains unclear whether a BM evaluation is necessary after normalization of the monoclonal (M) protein from the serum and/or urine by immunofixation. The authors retrospectively identified 92 patients with a detectable M protein who subsequently achieved treatment-related normalization and had a restaging BM test. They found that 14% of patients still had 5% or more BM plasma cells despite M protein normalization. A subset had serum light chain (FLC) assay tested. Even in those where the FLC assay normalized, 10% still had increased BM plasma cells after treatment. Overall survival from the time of negative M protein was inferior for those with greater than 5% marrow plasma cells (p = 0.01). BM examination after normalization of the M protein in myeloma should not be routinely abandoned.
Source: Chee C, et al. The importance of bone marrow examination in determining complete response to therapy in patients with multiple myeloma. Blood 2009;114:2617-2618.
Multiple myeloma (MM) is a plasma cell dyscrasia characterized by a monoclonal gammopathy, clonal bone marrow (BM) plasma cells, and organ impairment (i.e., hypercalcemia, renal insufficiency, anemia, lytic lesions of the bone, and/or bacterial infections).1 Treatment response provides important clinical and prognostic information. The International Myeloma Working Group (IMWG) defines complete response (CR) as the absence of serum or urine monoclonal protein by immunofixation (IFE) and less than 5% plasma cells in the BM.2 A complete evaluation, including a BM examination, is essential for patients enrolled in clinical trials. However, the need for routine BM in clinical practice after eradication of a monoclonal protein is not clear.
A retrospective review was performed among patients with MM and a detectable monoclonal protein (defined as serum M protein > 1 g/dL and urine M protein > 0.2 g/day) at diagnosis who achieved an undetectable serum and urine M protein and had a BM evaluation performed at that time. Ninety-two patients were identified, with a median age of 59 years. The median serum and urine M protein level was 2.3 g/L and 0.3 g/day, respectively. Therapies enabling a negative M protein by IFE included high-dose therapy and transplantation (55%), initial induction with or without immunomodulatory agents (28%), second-line therapy (11%), and unknown (5%). Chee et al revealed 79 of 92 (86%) patients achieving a negative serum and urine IFE also achieved less than 5% BM plasma cells. Thus, 13 of 92 (14%) having a negative IFE actually had 5% or more BM plasma cells. In 11 of these 13, immunofluorescent studies confirmed plasma cell clonality. Three patients had greater than 10% plasma cells. There were also 29 patients who had a normal serum-free light-chain ratio. Of these, 26 of 29 (90%) had fewer than 5% BM plasma cells. Conversely, three of 29 (10%) had more than 5% plasma cells, even with a negative M protein and normal-free light-chain ratio.
Overall survival from onset of negative serum and urine IFE was 6.2 years in patients having less than 5% BM plasma cells, compared to 2.3 years in patients with 5% or more BM plasma cells (p = 0.01), although median progression-free survival did not differ (p = 0.7).
Commentary
The growth in active agents for MM has increased the ability to achieve high-level responses. The ability to evaluate disease status by monitoring the M protein by serum and urine assays enables non-invasive testing of response. Further free light-chain assays have added another diagnostic tool and may lead some clinicians to abandon bone-marrow examination except for diagnosis. The question emerges whether repeating a BM examination has practical relevance should treatment render the M protein component undetectable.
Chee et al studied 92 patients with a detectable M protein by serum or urine IFE before treatment who, after therapy, achieved negative levels and had a BM performed. Of these patients, 13 of 92 (14%) had 5% or more BM plasma cells. In the subset where the serum light-chain ratio was available, normalization of this assay did not exclude the presence of residual plasma cells, as 10% of such patients still had 5% or more residual BM plasma cells. Confirming the value of identifying residual BM plasma cells after normalization of the M protein, overall survival was worse for patients who had 5% or more BM plasma cells compared to those having fewer than 5% plasma cells.
This observational study has several limitations. First, Chee et al point out that only unilateral BM examinations were performed. Sampling error may lead to underestimating the actual number of patients with increased residual BM plasma cells once a negative M protein is achieved. Alternatively, this observational study may overestimate the actual problem. For example, if a patient achieved negative serum and urine IFE but a bone marrow was not performed, the patient would be excluded. Clinicians may well have performed marrows in patients at higher risk of residual disease.
The data also raise several interesting questions. First, one wonders whether BM plasma cells existing after normalization of an M protein are simply non-secretory or more complex mechanisms are at play. Further, since survival appeared worse if 5% or more plasma cells were detected, should consolidation or maintenance therapy be entertained? Further research is definitely needed in this area.
For MM patients who achieve a negative serum and/or urine M protein after therapy, repeat BM examination for residual plasma cells may still be of value.
References
1. Criteria for the classification of monoclonal gammopathies, multiple myeloma and related disorders: A report of the International Myeloma Working Group. Br J Haematol. 2003;121:749-757.
2. Durie BG, et al. International uniform response criteria for multiple myeloma. Leukemia. 2006;20:1467-1473.
Formal criteria for a complete response (CR) in multiple myeloma (MM) require a bone-marrow (BM) examination showing < 5% plasma cells. It remains unclear whether a BM evaluation is necessary after normalization of the monoclonal (M) protein from the serum and/or urine by immunofixation.Subscribe Now for Access
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