Patients Say Benefits of Brentuximab Vedotin Offset Risk of Peripheral Neuropathy

Patients with lymphoma who are treated with brentuximab vedotin (BV) (Adcetris) often experience peripheral neuropathy (PN) as an adverse event and potentially dose-limiting toxicity. A novel study has shown that, despite the prevalence of this toxicity, these patients report that the better outcomes yielded from treatment with BV outweigh the risk of neuropathy.

Of 89 eligible patients in the study, 93% received single agent BV. The median number of BV doses was 5. Forty-three patients (48%) developed peripheral neuropathy. At a median follow-up of 12 months, the adverse event was resolved completely in 14 patients (33%). The median time to resolution was 13 weeks.

Sarah Nagle, MD, of the Lymphoma Program at the Abramson Cancer Center at the University of Pennsylvania, reported the findings at the 2017 Cancer Survivorship Symposium held January 27-28 in San Diego. Nagle and her research team sought to identify predictors of brentuximab vedotin—induced peripheral neuropathy (BIPN), whether it affected disease outcomes, and explore any psychosocial impacts of BIPN.

“Therapy was altered in 58% of patients due to BV,” the researchers noted, “but this did not affect overall survival (OS) or progression-free survival (PFS).”

Although not statistically significant, there was a numerical difference in both of the survival outcomes: the median PFS for patients whose therapy was altered due to BIPN was 6.2 months versus 12.4 months for those whose therapy was not altered (P = .09), and median OS was 25.8 months versus not reached, respectively (P = .11).

Of 18 patients surveyed on their symptoms, 14 (78%) reported BIPN. At a median follow-up of 24 months, 10 patients (71%) reported ongoing symptoms. For 50% of patients, quality of life was affected by BIPN.

However, despite these significant symptoms related to BIPN, all patients were reportedly satisfied with their decision to receive BV.

The researchers also investigated the effects of other factors—including age, sex, prior neurotoxic agent, underlying neuropathy, diabetes mellitus, or BMI—on the risk of developing BIPN. None of these factors were found to increase the risk for developing the adverse event. However, 3 additional factors were identified as being associated with BIPN: the number of BV doses, the cumulative dose, and treatment response.

These findings are based on a retrospective chart review, open-ended survey, and self-reported symptom assessment involving 89 lymphoma patients who received treatment at the cancer center between January 2010 and May 2016; of the total, 54% had Hodgkin lymphoma and 23% cutaneous T-cell lymphoma. Eligible patients were aged 18 years or older (median age, 48 years) and had 1 or more cycles of BV therapy (median, 5 doses); 71% of participants were treated with prior neurotoxic therapy.

Nearly half of the patients studied (n = 43) developed neuropathy; of these, 3 individuals had their BV held, 9 discontinued therapy, and 14 had their BV dose modified, Nagle reported in a poster presentation at the symposium. Forty-two percent of patients with BIPN used analgesics, and 6 were referred to a pain specialist.

The researchers also looked at more subjective commentary with respect to the psychosocial burden of neuropathy and elicited a range of responses, including difficulty with balance, pain after periods of long sitting or when getting up in the morning, a reliance on family members for tasks they can no longer perform, and finding the condition harder to deal with in the winter months than during the summer.

Some patients, however, said the condition was not limiting, whereas others acknowledged the symptom but said they had no regrets. “Despite significant symptoms from BIPN, all patients were satisfied with the decision to receive BV regardless of disease response,” the researchers reported.

“BIPN is a significant adverse effect in patients who receive BV, and it may fail to resolve in a large subset of patients,” they continued. Nonetheless, patients surveyed, “universally reported that the benefits of this therapy outweigh the risks. Clinicians should be aware of the risk for BIPN and educate patients accordingly,” concluded the researchers.

Nagle S, Strelec LE, Loren AW, et al. Brentuximab-induced peripheral neuropathy: risk factors and patient experiences. J Clin Oncol. 2017;35(suppl 5S; abstr 120).