Neutropenia Common in Lenalidomide/Dexamethasone-Treated Myeloma

Grade 3/4 neutropenia is a common adverse event experienced by patients undergoing treatment for relapsed, refractory multiple myeloma with lenalidomide and dexamethasone, a new study has found.

According to an observational study published in the American Journal of Hematology, about one-third of patients being treated with this drug combination will experience grade 3/4 neutropenia.

“Further efforts should be made in clinical trials and author consensus to improve the recommendations for neutropenia management in multiple myeloma patients receiving immunomodulatory therapy,” wrote researchers led by Xavier Leleu, MD, of Hôpital Claude Huriez, Lille, France.

The combination of lenalidomide/dexamethasone is a commonly used first-line treatment for patients with relapsed, refractory multiple myeloma. Previous research has shown that grade 3/4 neutropenia is a well-known adverse event associated with the use of this drug combination. Researchers conducted this study to estimate the incidence of neutropenia and explore how it is managed in this patient population.

They looked at safety outcomes from 198 patients with relapsed/refractory myeloma taken from 34 centers in nine countries. Patients were followed for 12 months from treatment initiation. Sixty-eight percent of patients were receiving 25 mg lenalidomide on a standard schedule.

Results showed that 31% of patients had grade 3/4 neutropenia and 50% of these patients reported three or more events within a year. Additionally, the researchers observed that patients on a non-standard lenalidomide schedule had a higher incidence of grade 3/4 neutropenia than those on a standard schedule.

“The incidence of grade 3/4 neutropenia increased with worsening renal function, suggesting that the recommended dose adjustment at the start of lenalidomide therapy for patients with impaired renal function is important to follow in clinical practice,” the researchers wrote.

Neutropenia occurred throughout lenalidomide treatment, with a median time to first neutropenia at 8.8 weeks.

The researchers conducted a multivariable analysis and found that patients with relapsed and refractory disease were four times as likely to experience grade 3/4 neutropenia than those with only relapsed disease (odds ratio, 3.92; P = .004). This increase is likely due to the fact that “relapsed and refractory myeloma represents a more advanced stage of disease, a factor commonly identified as a predictor of chemotherapy-induced neutropenia and febrile neutropenia in cancer patients,” the researchers wrote.

Leleu and colleagues also identified several characteristics that were more common in patients who experienced neutropenia such as lenalidomide exposure reduction, use of granulocyte-colony stimulating factor, unplanned hospitalization, and outpatient clinic visits.