Tumor Lysis Syndrome Risk May Rise With Use of Bortezomib for MM in Men

Therapy with bortezomib (Velcade) for multiple myeloma (MM) may increase the risk of tumor lysis syndrome (TLS) in male patients, according to a new study.

Patients with MM are considered to be at a low risk of developing TLS. However, in a new study, corresponding author Kazunori Kimura, PhD, of Nagoya City University Hospital, in Japan, and colleagues noted that some studies have suggested novel proteasome inhibitors such as bortezomib might increase the risk of TLS in patients with MM.

To study the matter, Kimura and colleagues completed a retrospective analysis of 210 patients who received primary therapy for treatment-naive, symptomatic MM between 2007 and 2020, looking for cases of laboratory TLS (LTLS) and clinical TLS (CTLS). The study is believed to be the largest of its kind to evaluate TLS risk in patients with MM. The findings were published in the journal BMC Cancer.

Of the 210 patients, 10 (4.8%) developed LTLS and 7 (3.3%) developed CTLS. Investigators said the anticancer or prophylactic antihyperuricemic agents used were similar between those who developed TLS and those who did not.

The authors found that bortezomib-containing therapy led to a significant increase in a patient’s risk of TLS (odds ratio [OR], 3.40; P = .069), as did being a male (OR, 2.29; P = .153).

The authors then conducted a subgroup analysis of the men in the study, and found bortezomib-containing therapy boosted the risk of TLS in the subgroup to an OR of 8.51 (P = .046).

Kimura and colleagues noted that their findings are in line with the findings in other cancers, where the type of therapy, rather than the type of cancer, seems to affect TLS risk.

“TLS risk for chronic lymphocytic leukemia (CLL) is classified as low; however, the risk increases to an intermediate level when targeted therapies (rituximab) or purine analogues (fludarabine) are used,” they wrote, adding that venetoclax has also been reported as being linked to higher rates of TLS.

The investigators noted that a previous study has also found that men with acute myelogenous leukemia had a higher risk of TLS compared to women. In that report, the authors suggested that higher levels of uric acid levels prior to the start of therapy might be the cause.

Kimura and colleagues thus decided to analyze pretreatment uric acid levels in their study. They found no significant link between uric acid and TLS.

“Thus, the increase in TLS risk in males cannot be fully explained by only uric acid levels,” they said.

Another possibility, the investigators said, is that genetic mechanisms related to urate excretion are at play.

The authors noted a number of limitations. Among them, certain clinical data were missing for some patients, making it difficult to estimate the incidence of TLS associated with phosphorus, for instance.

However, they said their data suggest a significant phenomenon, the cause of which should be further explored.

“TLS risk should be further evaluated in low-risk diseases such as MM, where the necessity of intensity of prophylactic therapy is not currently established, as an increasing number of novel anticancer therapies can achieve high antitumor responses,” the authors concluded.

Reference

Kondo M, Hotta Y, Yamauchi K. et al. Bortezomib administration is a risk factor associated with the development of tumor lysis syndrome in male patients with multiple myeloma: a retrospective study. BMC Cancer. Published online November 17, 2020. doi: 10.1186/s12885-020-07592-9