Response to therapeutic monoclonal antibodies for multiple myeloma in African Americans versus whites

Abstract

BACKGROUND: Myeloma occurs disproportionately in African Americans, with disparities in outcomes potentially caused by access to care, cytogenetics, and immunity. A gap in knowledge of immune function dissimilarities between African Americans and whites exists. Data for other diseases suggest innate differences in immunity and inflammatory markers, with potential implications for therapeutic monoclonal antibodies reliant on secondary immune activation for activity. METHODS: Patients receiving daratumumab or elotuzumab, lenalidomide, and dexamethasone were retrospectively studied with a primary endpoint of response at 2 (daratumumab) or 4 months (elotuzumab). Secondary endpoints included stable disease or better at the same points, treatment duration, time to best response, and adverse events. RESULTS: Eighty patients were included; baseline characteristics were balanced with the exception of the stage at diagnosis, which was more advanced in African Americans. No statistically significant difference in response was seen: 37.9% in whites versus 11.8% in African Americans with daratumumab (P = .090) and 60% in whites versus 44% in African Americans with elotuzumab (P = .462). There were no differences in the duration of treatment, the time to best response, or adverse events. Common potential immune-related adverse events in both arms were fatigue (39%), back pain (30%), and infusion reactions (40%). Anemia was significantly associated with a response to daratumumab (P = .02); no patients without anemia responded at 2 months, whereas 34.4% of patients with anemia did. CONCLUSIONS: No significant difference in response, duration of treatment, or time to response was seen by race, although a trend toward greater early response rates in whites was observed. In these cohorts, as in other analyses, African American patients tended to present with later stage disease. Cancer 2018;124: 4358-4365.

Reply to African American patients may or may not have poorer response rates after monoclonal antibody treatment: Overreliance on P values in underpowered studies

“…We appreciate the praise and thoughtful commentary from Mr. Fiala regarding our report on our experience with the therapeutic monoclonal antibodies daratumumab and elotuzumab in African American patients compared with white patients treated at the Winship Cancer Institute of Emory University . He expressed concern with our statistics and the conclusions we drew, specifically that a lack of statistical significance in our analyses does not necessarily mean no difference exists, or, stated another way, that the numeric differences we observed in the retrospective analysis may be real, and therefore clinically significant.…”

“…We considered this as well in our conclusion. Because our study was a retrospective analysis of a fixed cohort, we unfortunately did not have the ability to prospectively determine power calculations. We appreciate the power concerns noted by Mr. Fiala, and agree that additional studies are needed to assert definitive conclusions, as we stated.…”

African American patients may or may not have poorer response rates after monoclonal antibody treatment: Overreliance on P values in underpowered studies

“…The authors found that the respective overall response rates (ORRs), defined as a partial response or better, to single‐agent daratumumab was only 11.8% (2 of 17 patients) for African Americans compared with 37.9% (11 of 29 patients) for whites. Similarly, the ORR for African American patients receiving the combination of elotuzumab, lenalidomide, and dexamethasone was only 44.4% (4 of 9 patients) compared with 60% (15 of 25 patients) for whites . However, neither of these differences was statistically significant, leading the authors to conclude that both races have similar responses to treatment with MoAbs.…”

“…In the current study, it is possible that the findings are purely spurious. They also could be due to imbalances in patient demographics: African American patients were >3 times more likely to have International Staging System stage III disease compared with white patients . Additional studies are needed to adjudicate this.…”

“…Chehab et al do note in their discussion of study limitations that the small sample sizes “makes it challenging to assert definitive conclusions.” I would argue that underpowered studies should be used to generate hypotheses rather than draw conclusions. Within the context of the study by Chehab et al, concluding that there may be differences in response rates between white and African American patients is as logical as concluding that there are not. Underpowered studies can provide data regarding important topics such as this; however, researchers should avoid making conclusions based solely on P values.…”