Treatment-Related Neuropathy Following Brentuximab-Vedotin in African Americans Treated for Lymphoma: A Retrospective Chart Review

INTRODUCTION: Brentuximab-vedotin (BV), an anti-CD30 antibody-drug conjugate, has proven to be an effective treatment for CD30-expressing lymphomas. The toxicity profile of BV has been widely characterized in clinical trials and retrospective studies, although there is limited data in African American (AA) populations. In this study, we looked at the incidence and severity of BV chemotherapy-induced neuropathy (CIN) in AA patients in comparison to historical data.

METHODS: We conducted an IRB-approved retrospective medical record analysis to investigate the occurrence and severity of CIN in AA patients with newly diagnosed or recurrent lymphoma treated with BV at Grady Memorial Hospital. Records of all BV administrations were examined from August 2011 to June 2024. Our analysis was limited to AA patients over the age of 18 years with available electronic health records and at least one BV administration. Patient demographics (age at first BV, gender, race, ethnicity, and comorbidities) and chemotherapeutic drugs used were recorded. Neuropathy status was abstracted from clinic notes and graded based on the Common Terminology Criteria for Adverse Events (CTCAE) grading scale. Neuropathy grade at baseline, during and at the end of treatment, and additional indicators of worsening neuropathy (e.g., initiation of medications to relieve CIN, treatment interruptions, dose reductions and discontinuation due to CIN) were measured.

Analysis compared the incidence of neuropathy in AA to pooled historically published rates of BV (Velasco et al. Cancers (Basel). 2021 Dec 5;13(23):6125). To determine the statistical significance of differences between the rate of CIN in our cohort and those historically reported, we employed a Chi-Square test for categorical variables with an alpha level set at 0.05.

RESULTS: Thirty-nine patients were treated with BV in our center. Of these, 32 were AA and were included for analysis. Twenty (63%) patients were men and the median age at time of BV initiation was 41 (range 20-69) years. Twenty-one (66%) patients had Hodgkin Lymphoma and 11 (34%) had Non-Hodgkin Lymphoma (5 Anaplastic Large Cell Lymphoma, 1 CD30+ B-cell lymphoma, 2 Mycoses Fungoides, and 3 CD30+ Peripheral T-cell Lymphoma).

Fourteen (43%) patients experienced neuropathy during treatment; 8 (25%) had baseline neuropathy (of any grade) prior to BV treatment. Of these 14 patients, 12 (37.5%) experienced new or worsening CIN by the end of treatment. Three (9%) patients experienced severe grade ≥3 CIN during treatment; 5 (16%) required new medications to relieve neuropathy symptoms. Twenty-one (66%) of the 32 patients successfully completed all their planned BV treatments.

Seven (21%) required dose reductions of BV due to side effects, three of which were due to CIN; two ceased treatment entirely due to CIN. The most common (>10%) comorbidities were HIV (n=9, 28%) and diabetes mellitus (n=4, 12.5%). The most common non-BV chemotherapy exposures were: doxorubicin (69%), dacarbazine (53%), vinblastine (50%), cyclophosphamide (28%), nivolumab (6%), etoposide (3%), rituximab (3%), gemcitabine (3%), bleomycin (3%), and vincristine (3%).

Our AA cohort had a CIN rate (43.5%) higher than published data: this rate is significantly higher than pooled historical data for BV monotherapy (15.4%, n/N = 245/1607, p < 0.001) and trended to be higher than combination therapy (28.4%, n/N = 48/169, p = 0.08), though it was not statistically significant.

Twelve (37.5%) of our 32 patients experienced worsening neuropathy compared to baseline; in pooled historical reports, when BV was used as monotherapy, this rate was 20% (n/N = 322/1607, p = 0.111); when BV was used in combination, this rate was 7.1% (n/N = 12/169, p = 0.0620). In our dataset, 9.4% (n/N = 3/32) of patients developed grade ≥3 CIN compared to a 7.1% historical rate in patients getting BV in combination (n/N = 12/169, p = 0.653) and 3.5% in those receiving BV alone (n/N = 57/1607, p = 0.0822).

CONCLUSION: This is the first study to show that AA patients have grater rates of CIN with BV than in historical reports in which they have been underrepresented. This was a single-center study, but future attempts are underway to broaden the AA patient sample across multiple locations to better describe the differences in BV-induced CIN in AA compared to non-AA populations.