Contributions
Abstract: PB1674
Type: Publication Only
Session title: Myeloma and other monoclonal gammopathies - Clinical
Background
Based on anecdotal reports of raised serum parathyroid hormone (PTH) levels in some patients with multiple myeloma, we set out to investigate if this is a common finding.
Aims
To establish if parathyroid hormone levels act as predictors of outcome in multiple myeloma.
Methods
Patients with newly diagnosed multiple myeloma at Cambridge University Hospitals between 2015 and 2021 were identified from electronic records (EPIC). Blood parameters including paraprotein, PTH, beta-2 microglobulin (β2M), albumin and others, recorded near the time of diagnosis were collected. We use the International Staging System (ISS), defined as, ISS stage I: β2M < 3.5 mg/L and albumin ≥ 35 g/dL, ISS stage II: neither I or III, ISS stage III: β2M ≥ 5.5 mg/L and our novel 'ISS+PTH' score, calculated from a sum of: β2M < 3.5 mg/L (0), ≥ 3.5 mg/L (1); PTH < 10 pmol/l (0), ≥ 10 pmol/l (1); albumin < 35 g/dL (1), ≥ 35 g/dL (0). We use Pearson correlation and Kaplan-Meier survival analyses to investigate factors that correlate with PTH levels and assess their impact on prognosis.
Results
We identified 1066 patients with multiple myeloma (640 men/426 women). Median age at diagnosis was 70 years and median survival was 832 days. Of these, 182 had PTH levels assayed at diagnosis. Median serum PTH level was 4.77 pmol/l (range 0-103.3 pmol/l) and 35 patients had PTH >10 pmol/l. Median survival for those with PTH >10 pmol/l was 859 days, compared to those with PTH <10 pmol/l, with a median survival of 1495 days (p<0.229). PTH level significantly correlated with creatinine and other parameters (Table 1A).
To understand if PTH levels can enhance the predictive power of the International Staging System (ISS), we compared the performance of the ISS score to a modified score including PTH as a variable, applied to participants for whom all relevant tests were available. We noted that β2M and albumin levels correlated significantly to each other (r=-0.37), raising the possibility that additional variables could be used to refine prognosis. Therefore, we tested if PTH could be added to ISS and re-stratified patients into 4 categories (Table 1B). Upon incorporation of PTH, we found that distribution across the classes was similar, but the worse prognostic group faired significantly worse (Table 1B). As noted by the mean survival differences between ISS and ISS+PTH, we observed better separation of the categories on survival curves by the latter. Of particular note, 17 patients with a very high PTH (>15 pmol/l) had a significantly poorer mean survival of 368 days and high median values for albumin (28.5 g/L), β2M (12.2 mg/L), creatinine (258 umol/L) and Corrected Calcium (2.35 mmol/L).
Conclusion
Collectively, our findings show that PTH levels correlate with other parameters and do not significantly improve the prognostic ability of the ISS score overall, but do identify a group with particularly poor prognosis. PTH has a very short half-life of 5 minutes, as it is rapidly cleared by the liver and kidney, so the correlation with creatinine and urea may allude to renal failure being at least partially responsible for PTH accumulation. In addition, our findings show that PTH levels in multiple myeloma are often inappropriately elevated in relation to the prevailing calcium level, a factor that can contribute to the cytokine-driven myeloma bone disease. Therefore, will next investigate the impact of inappropriately raised PTH on myeloma bone disease per se and any clinical/therapeutic implications this may have on patient management.
Keyword(s): Multiple myeloma, Prognosis
Abstract: PB1674
Type: Publication Only
Session title: Myeloma and other monoclonal gammopathies - Clinical
Background
Based on anecdotal reports of raised serum parathyroid hormone (PTH) levels in some patients with multiple myeloma, we set out to investigate if this is a common finding.
Aims
To establish if parathyroid hormone levels act as predictors of outcome in multiple myeloma.
Methods
Patients with newly diagnosed multiple myeloma at Cambridge University Hospitals between 2015 and 2021 were identified from electronic records (EPIC). Blood parameters including paraprotein, PTH, beta-2 microglobulin (β2M), albumin and others, recorded near the time of diagnosis were collected. We use the International Staging System (ISS), defined as, ISS stage I: β2M < 3.5 mg/L and albumin ≥ 35 g/dL, ISS stage II: neither I or III, ISS stage III: β2M ≥ 5.5 mg/L and our novel 'ISS+PTH' score, calculated from a sum of: β2M < 3.5 mg/L (0), ≥ 3.5 mg/L (1); PTH < 10 pmol/l (0), ≥ 10 pmol/l (1); albumin < 35 g/dL (1), ≥ 35 g/dL (0). We use Pearson correlation and Kaplan-Meier survival analyses to investigate factors that correlate with PTH levels and assess their impact on prognosis.
Results
We identified 1066 patients with multiple myeloma (640 men/426 women). Median age at diagnosis was 70 years and median survival was 832 days. Of these, 182 had PTH levels assayed at diagnosis. Median serum PTH level was 4.77 pmol/l (range 0-103.3 pmol/l) and 35 patients had PTH >10 pmol/l. Median survival for those with PTH >10 pmol/l was 859 days, compared to those with PTH <10 pmol/l, with a median survival of 1495 days (p<0.229). PTH level significantly correlated with creatinine and other parameters (Table 1A).
To understand if PTH levels can enhance the predictive power of the International Staging System (ISS), we compared the performance of the ISS score to a modified score including PTH as a variable, applied to participants for whom all relevant tests were available. We noted that β2M and albumin levels correlated significantly to each other (r=-0.37), raising the possibility that additional variables could be used to refine prognosis. Therefore, we tested if PTH could be added to ISS and re-stratified patients into 4 categories (Table 1B). Upon incorporation of PTH, we found that distribution across the classes was similar, but the worse prognostic group faired significantly worse (Table 1B). As noted by the mean survival differences between ISS and ISS+PTH, we observed better separation of the categories on survival curves by the latter. Of particular note, 17 patients with a very high PTH (>15 pmol/l) had a significantly poorer mean survival of 368 days and high median values for albumin (28.5 g/L), β2M (12.2 mg/L), creatinine (258 umol/L) and Corrected Calcium (2.35 mmol/L).
Conclusion
Collectively, our findings show that PTH levels correlate with other parameters and do not significantly improve the prognostic ability of the ISS score overall, but do identify a group with particularly poor prognosis. PTH has a very short half-life of 5 minutes, as it is rapidly cleared by the liver and kidney, so the correlation with creatinine and urea may allude to renal failure being at least partially responsible for PTH accumulation. In addition, our findings show that PTH levels in multiple myeloma are often inappropriately elevated in relation to the prevailing calcium level, a factor that can contribute to the cytokine-driven myeloma bone disease. Therefore, will next investigate the impact of inappropriately raised PTH on myeloma bone disease per se and any clinical/therapeutic implications this may have on patient management.
Keyword(s): Multiple myeloma, Prognosis