Proteasome inhibitors (PIs) have revolutionized the treatment of multiple myeloma and are a backbone of therapy. Bortezomib, the first PI approved, has shown efficacy in both front-line and relapsed/refractory settings however the development of resistance and side effects such as peripheral neuropathy can limit its use. The second generation PIs carfilzomib and ixazomib, both approved in relapsed/refractory cases, may help to overcome resistance mechanisms and increase tolerability. While bortezomib is approved to be administered intravenously (IV) or subcutaneously (SC) and carfilzomib IV, ixazomib is the first and only approved PI that is orally bioavailable. Areas covered: This review focuses on the safety data from clinical trials for the three approved PIs and how to manage adverse effects. A summary of efficacy data from select clinical trials is also included. Expert commentary: Targeting the proteasome/ubiquitin system is a validated and important part of current anti-myeloma therapy. The availability of an oral proteasome inhibitor without significant neuropathy as a side effect offers patients an important step forward over their treatment.

Monoclonal antibodies (elotuzumab and daratumumab) are the newest class of drugs that have proven to be efficacious antimyeloma agents. Although daratumumab, a CD38 monoclonal antibody, has established its efficacy as a single agent and in combination with immunomodulatory agents and proteasome inhibitors, elotuzumab (signaling lymphocytic activation molecule F7 monoclonal antibody) has proven activity in combination with lenalidomide and dexamethasone. Infusion-related reactions (respiratory and nonrespiratory) seem to be a common theme of adverse events with monoclonal antibodies, although the relative incidence differs across these two agents. Identifying the appropriate pre- and postinfusion medication strategies can help lower the rates of infusion-related reactions and facilitate reduction in infusion times. In this article, we review the incidence of the infusion-related reactions with elotuzumab and daratumumab and their clinical activity in myeloma, review our institutional experience of management of infusion-related reactions, and provide some practical mitigation strategies to reduce their incidence.

We examined treatment with or without anthracyclines in 72 eldery diffuse large B-cell lymphoma patients (age ≥ 65 years) in a retrospective cohort analysis. Factors leading to treatment without an anthracycline included age and ejection fraction, whereas markers of tolerability were similar between groups. This study highlights the details of anthracycline tolerability in elderly lymphoma patients. Introduction Although diffuse large B-cell lymphoma (DLBCL) can be cured with rituximab and anthracycline-based therapy, within the elderly population there are additional factors to consider in selecting a treatment regimen including comorbid conditions, decreased drug metabolism, decreased hematologic reserve, reduced performance status, and regimen-related toxicity. Patients and Methods We performed a retrospective cohort analysis of patients with DLBCL aged ≥ 65 years at time of diagnosis treated with either an anthracycline-containing regimen (ACR; n = 59) or a non-ACR (n = 13) to assess factors that led to treatment selection, tolerability, and outcomes. Results The mean age was 73 years in the ACR and 77 years in the non-ACR group (P = .009), and median left ventricular ejection fraction (LVEF) at diagnosis was 60% in the ACR group and 45% in the non-ACR group (P < .001). With an ACR, elderly DLBCL patients had a median overall survival of 28 months and a 2-year progression-free survival (PFS) of 64%. After an ACR, 14 patients [24%] (out of 59 total patients) had a decrease in LVEF, 7 patients [15%] (% is based off of those who we had the data collected, so this is out of 45 with this specific data) required a dose reduction of the anthracycline, and 15 patients [33%] (% is based off of those who we had the data collected, so this is out of 45 with this specific data) could not complete the regimen as planned. Hospitalization due to toxicity occurred in 20 patients [44%] (% is based off of those who we had the data collected, so this is out of 45 with data) of patients in the ACR group and 3 patients [75%] (% is based off of those who we had the data collected, so this is out of 4 with this specific data) in the non-ACR group, and was the only predictor of overall survival. Conclusion Results of this study suggest that elderly patients with DLBCL experience meaningful PFS with ACRs, but a third experience toxicity requiring therapy modification. Future studies should examine larger patient populations and define treatments with outcomes similar to ACR that also decrease toxicity and hospitalization in the elderly DLBCL population.

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.