Early Mortality in Newly Diagnosed Multiple Myeloma in the Context of Novel Drugs

Background:  In 2015, there will be an estimated 26,850 cases of multiple myeloma (MM) diagnosed in the US.  Novel therapies and broader use of autologous stem cell transplant (SCT) have resulted in improved survival.  Despite this tremendous progress in its treatment, MM remains incurable and there are patients whose survival is quite limited.  We reviewed our Institution’s experience by examining a 10-year cohort of 836 patients treated for MM at Massachusetts General Hospital (MGH) to synthesize our cumulative findings, specifically looking for baseline characteristics associated with early mortality (EM), defined as death within two years of diagnosis.

Methods:  Retrospective review of 836 MM patients treated in the MGH Cancer Center between 2005 and 2015 to identify patients who died of MM.  Inclusion criteria for this analysis were age of 18 or greater treated for MM between 2005 and 2015 at MGH who died of their disease.  The outcomes of interest were median survival, gender, race, marital status, insurance status, body mass index (BMI), stage at diagnosis, presence of bone disease at diagnosis, renal function, type of MM, cytogenetics (by  karyotype and fluorescent in situ hybridization), first-line therapy, best response to first-line therapy, and treatment with high-dose chemotherapy (HDC) and autologous stem cell transplant (SCT).  A Fisher’s exact test was used to assess the statistical significance of the compared study measurements.

Results:  One hundred thirteen patients who died of MM were identified, of those, 36 (32%) died within 2 years of diagnosis.  Median survival for those who died within 2 years was 0.997 versus (vs) 4.15 years.  Median age of the EM cohort was 68.9 vs 64.6 (p=0.07).  Bone disease at diagnosis was strongly associated with EM, 24 (67%) vs 13 (19%) (p<0.0001).  Patients who died within 2 years were more likely to have advanced stage disease by the International Staging System (ISS) criteria. ISS stages in the EM group were ISS I, 4 (11%), ISS II, 9 (25%), ISS III, 23 (64%)  III vs ISS I, 18 (27%), ISS II, 22 (33%), and ISS III, 26 (39%) (p=0.05).  Pts in the EM group had diminished renal function at diagnosis, estimated glomerular filtration rates were: <60 in 25/35* (71%) in the EM group vs 26/67 (39%) (p=0.006). Type of first-line therapy was not significantly different between the two cohorts (p=0.07), however, response to first-line therapy was poorer in the EM group:  4 CR (11%), 5 VGPR (14%), 16 PR (44%), 10 SD (28%), 1 PD (3%) vs 25 CR (37%), 10 VGPR (15%), 25 PR (37%), 5 SD (7%), and 2 unknown (p=0.007).  Transplant-eligible patients were less likely to receive HDC and SCT in the EM group 5 of 14 (36%) vs 27 of 39 (69%) (p=0.004).  High-risk cytogenetics were not associated with EM, 7/36 (19%) versus 13/67 (19%) (p>0.99).  Gender, race, marital status, type of insurance, and BMI were not significantly different between the two groups.

Conclusions: EM in MM is associated with advanced ISS stage, bone disease, and diminished renal function at diagnosis.  Interestingly, high-risk cytogenetics were not associated with EM which may be a reflection of small numbers.  There was a significant difference in the number of pts who received HDC and SCT which is likely related to baseline co-morbid conditions such as diminished renal function.  The correlation between the presence of bone disease with survival underscores the importance of incorporating bone disease into the ISS staging system.

*eGFR data missing from one patient