Age, Infection, Cardiac Disease Linked to Early Death for Patients With Newly Diagnosed Multiple Myeloma

Advances in treatment of multiple myeloma (MM) have improved survival and allowed many patients to live with this disease as a chronic condition. But some groups—the oldest patients, and those with certain comorbidities—remain at risk of early death, despite advances such as protease inhibitors, immunomodulatory drugs, and autologous stem cell transplant.

Results from a registry study of patients from Australia and New Zealand show that 9.1% of patients with a new diagnosis of MM died within a year of diagnosis, and infection contributed to early death in 38% of cases in which a cause of death was reported.

Published Monday in the British Journal of Haematology, the study led by Zoe McQuilten, associate professor at Monash University in Melbourne, examined 2377 patients with newly diagnosed MM (NDMM) at 36 institutions in Australia and New Zealand between July 2011 and March 2020. Investigators defined early mortality as death from any cause within 12 months of diagnosis. They found that 216 patients (9.1%) died in the first year, with 4.5% having died within the first 6 months after diagnosis with MM.

The study authors identified several independent predictors of early mortality from MM, which included the patient’s age, Eastern Cooperative Oncology Group (ECOG) performance status, and cancer stage; other factors were the presence of cardiac disease or low serum albumin levels, which can be an indicator of kidney or liver disease.

Cause of death was reported in 193 (89%) of the patients, and secondary cause of death was available for 69 patients (32%). Infection contributed to early death in more than a third of the cases for which a cause of death was available, the authors wrote. Factors related to disease progression were cited in 151 cases (78%), and infection in 13 cases (7%). However, infection was cited as a “contributing factor” for early death in 38% of the patients.

Common infections in MM include meningitis, septicemia, pneumonia, osteomyelitis, cellulitis, and pyelonephritis. The risk of infection for patients can range from 10-fold to 18-fold higher in the first year after diagnosis.

Detailed results showed the following:

• Among all patients, the median (IQR) age was 67.4 (58.9-74.6) years; among those with early death, the median age was 77.3 (69.1-83.0) years, whereas the median age for those with 12-month survival was 66.5 (58.4-73.6) years, for an odds ratio (OR) of 1.04 (95% CI, 1.02-1.06; P < .001).
• Among all patients, the percentage having an ECOG status of 2 to 4 was 7.5%; among those with early death, it was 25.4%, vs 5.7% for those with 12-month survival, for an OR of 1.50 (95% CI, 1.26-1.89; P < .001).
• Among all patients, 30.7% had stage III disease at diagnosis based on the International Staging System (ISS). Among those with early death, 55.0% had reached stage III when nearly diagnosed, compared with 28.7% who achieved 12-month survival; the OR was 1.40 (95% CI, 1.07-1.82; P = .01).
• Among all patients, 10.6% had cardiac disease; however, 24% had cardiac disease among those with early death, compared with 9.3% of those with 12-month survival, for an OR of 1.96 (95% CI, 1.35-2.86; P < .001).
• Median serum albumin levels for all patients were 34.0 g/L, which is the lowest end of the range considered normal (34 to 54 g/L). The median level for patients experiencing early death was 30.0 g/L, compared with 34.0 for patients who had 12-month survival, for an OR of 0.95 (95% CI, 0.93-0.98; P < .001).

The authors concluded that despite the many advances in MM, more work is needed to identify treatments for those patients who remain at high risk of early death.

“These findings support the need for future research into optimizing treatment delivery to elderly and/or frail patients with NDMM and the ongoing unmet need for more effective and deliverable treatment modalities, particularly in the elderly MM population,” they wrote.

Reference

McQuilten Z, Wellard C, Moore E, Augustson B, Bergin K, Blacklock H, et al. Australian and New Zealand Myeloma and Related Diseases Registry. Predictors of early mortality in multiple myeloma: results from the Australian and New Zealand Myeloma and Related Diseases Registry (MRDR). Br J Haematol. Published online July 11, 2022. doi.org/10.1111/bjh.18324