Severe Renal Impairment Worsens Outcomes in Multiple Myeloma

Severe renal impairment (RI) is associated with decreased rates of survival among patients with multiple myeloma (MM), even if renal function is restored with therapy, according to new research.

Investigators from Fujian Medical University Union Hospital in China found patients who achieved restoration of renal function recovery had somewhat better odds of survival, though they said those patients still had worse outcomes than patients who did not suffer severe renal impairment. The findings were published in the Journal of Clinical Laboratory Analysis.

Corresponding author Lixin Wei, MD, PhD, and colleagues noted that up to 40% of patients who are newly diagnosed with MM suffer from RI, the causes of which can include cast nephropathy, light chain deposition disease, amyloidosis, and hypercalcemia, among other factors.

The International Myeloma Working Group (IMWG) has defined RI as creatinine clearance <40 mL/min, and has stated that estimated glomerular filtration rate (eGFR) could be used to quantify creatinine clearance. In earlier studies, “severe” RI has typically been defined as eGFR <30 mL/min, the authors said.

In this study, Wei and colleagues sought to use both the IMWG’s definition of RI and the eGFR <30 mL/min criteria for severe RI in order to see the extent to which RI affected prognoses, and whether there were differences between severe RI and less-than-severe RI. They also evaluated the extent to which therapeutic choices affected overall survival (OS).

To do so, the investigators retrospectively analyzed 393 newly diagnosed patients with MM who sought treatment at their hospital between 2012 and 2018.

They found that a number of factors were associated with a lower chance of survival: severe RI, hemoglobin <100 g/L, LDH ≥ 245 U/L, hyperuricemia, 1q21 amplification, and lack of novel agent treatment.

Patients who had severe RI had a median OS of 27 months if they were able to achieve a renal response with therapy. Those who did not receive a renal response had a median OS of just 18 months. However, both groups had worse outcomes than patients without severe RI, who had a median OS of 51 months. Those with mild RI at diagnosis had a median OS of 35 months.

“We found that even if MM patients with severe RI experienced a restoration of renal function after therapy, they did not have equivalent survival outcomes to patients without severe RI,” Wei and colleagues wrote.

The authors also found that bortezomib-based therapies resulted in higher renal response rates than regimens that did not include bortezomib (Velcade). The authors said their data suggested that novel agents plus autologous stem cell transplant (ASCT) led to better outcomes compared to novel agents without transplantation.

“However, there has been increasing debate on the role of ASCT in the current era with the superior efficacy of the novel agent,” Wei and colleagues said. “Therefore, ongoing trials will continue to define the role of ASCT in MM patients in the future.”

One limitation of the study was that the analysis did not include comorbidities that could also be implicated in decline of renal function and may have affected OS. The study also included a statistically insignificant number of patients on carfilzomib-based regimens, and thus they were unable to analyze its impact on OS in patients with severe RI.

Reference
Chen X, Luo X, Zu Y, et al. Severe renal impairment as an adverse prognostic factor for survival in newly diagnosed multiple myeloma patients. J Clin Lab Anal. Published online July 25, 2020. doi:10.1002/jcla.23416.