Current recommendations for monitoring disease progression and response to treatment of immunoglobulin producing tumors in humans includes evaluation of serum or urine paraprotein (M-protein) concentration, involved free light chains and tumor size. Densitometry, the preferred method for qualifying M-proteins in human medicine, has recently been validated for use in the dog and was shown to outperform Ig-class specific radial immunodiffusion (RID) and ELISA based methods. A retrospective pilot study was performed to evaluate the applicability of the human based International Myeloma Working Group (IMWG) response criteria in dogs with multiple myeloma.
Archives from 2016 through 2019 were reviewed for canine cases with a diagnosis of multiple myeloma, M-protein documented by serum protein electrophoresis (SPE) and immunofixation (IF) of an initial sample, and subsequent electrophoretic evaluation of serial samples. M-proteins were quantified densitometrically from the electrophoretic study. When M-protein was not discernable on serial samples by SPE alone, repeat IF was performed, according to IMWG recommendations. Change in M-protein concentration was calculated and case progression was characterized using the IMWG response criteria. Available clinical history was reviewed. Survival was calculated as the time from initial electrophoretic evaluation to death or last known contact.
Fifteen cases met inclusion criteria. This included a total of 69 SPE evaluations. A pre-treatment sample was evaluated in ten cases. All cases received some form of chemotherapy but this was not standardized. One case had a presumed solitary lesion with attempted surgical excision, but histopathology documented incomplete excision and chemotherapy was instituted. Total protein was within normal limits in 39 of 69 samples. Biochemically derived globulins were measured in 27 samples and were within normal limits in 13 samples. Complete response (CR, lack of M-protein by SPE and IF), was documented in one case. Six cases achieved very good partial response (VGPR, M-protein decreased by > 90% but still detectable by IF) and an additional four cases met the criteria for a partial response (PR, 50-90% M-protein reduction). The cases that attained CR, VGPR or PR survived longer (median 630 days) than those that did not meet partial response criteria (M-protein change did not attain 50% decrease, median 333 days), log rank p = 0.013, Figure 1. During treatment, four cases had M-protein defined progressive disease ( > 25% and minimal 0.5 g/dL M-protein increase) which correlated with concurrent or subsequent clinical deterioration.
The majority of canine cases met IMWG criteria for a VGPR or PR although it is notable that only one dog achieved a CR. Preliminary data indicates that evaluation of electrophoresis-based M-protein detection and quantification using the human response criteria is possible in dogs with multiple myeloma and suggests that response measured in this manner correlates with survival. Evaluation of a larger cohort of cases in a prospective study is warranted.
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