Impact of Black Race on Peripheral Neuropathy in Patients With Newly Diagnosed Multiple Myeloma Receiving Bortezomib Induction.

PURPOSE: The incidence of multiple myeloma (MM) is two to three times higher in Black patients compared with other races, making it the most common hematologic malignancy in this patient population. Current treatment guidelines recommend the combination of a proteasome inhibitor, an immunomodulatory agent, and a corticosteroid as preferred induction therapy. Bortezomib use comes with the risk of peripheral neuropathy (PN) and potential need for dose reduction, therapy interruption, and additional supportive medications. Known risk factors for bortezomib-induced peripheral neuropathy (BIPN) include diabetes mellitus, previous thalidomide, advanced age, and obesity. We aimed to determine the potential association between Black race and incidence of BIPN. PATIENTS AND METHODS: We identified a cohort of 748 patients with newly diagnosed MM who received induction with bortezomib, lenalidomide, and dexamethasone from 2007 to 2016. One hundred forty Black patients were matched with 140 non-Black patients on age, sex, BMI, and route of bortezomib administration. Incidence of BIPN was a binary event defined as new use of a neuropathy medication, bortezomib dose reduction, dose omission, or discontinuation because of PN. RESULTS: The incidence of BIPN was higher in Black patients (46%) compared with non-Black patients (34%; P = .05) in both univariate (odds ratio [OR], 1.61; 95% CI, 1.00 to 2.61; P = .052) and multivariable analyses (OR, 1.64; 95% CI, 1.01 to 2.67; P = .047). No significant differences in BIPN were seen when stratified by route of administration. CONCLUSION: These data indicate that Black race is an independent risk factor for the development of BIPN. Additional prevention strategies, close monitoring, and appropriate supportive care measures are warranted for these patients.

Impact of concurrent gabapentin or pregabalin with high-dose melphalan in patients with multiple myeloma undergoing autologous hematopoietic stem cell transplant.

BACKGROUND: Melphalan is an alkylating agent used in both autologous (ASCT) and allogeneic stem cell transplantation. It is a substrate of L-type amino acid transporter-1 (LAT-1) and LAT-2, which are involved in its tissue penetration and elimination. Gabapentin and pregabalin, common concomitant medications in patients with multiple myeloma undergoing ASCT, are also substrates of LAT transporters, raising concern for potential competitive inhibition of melphalan transport. We evaluated whether concurrent use of gabapentin or pregabalin in patients receiving high-dose melphalan (≥140 mg/m2 ) prior to ASCT impacted frequency and severity of melphalan-related adverse events. OBJECTIVE: We aimed to determine if concurrent administration of gabapentin or pregabalin and melphalan increased melphalan toxicity. METHODS: This was a single-center, retrospective evaluation including patients ≥18 years of age who received high-dose melphalan as part of a conditioning regimen at the Winship Cancer Institute of Emory University between August 1, 2010 and April 1, 2020 and were followed through their transplant admission. After identification and inclusion of patients who received melphalan in combination with gabapentin or pregabalin, patient matching based on age (±5 years), sex, and melphalan dose (140 mg/m2 or 200 mg/m2 ) was utilized to generate a comparable cohort of patients who received melphalan alone. The primary outcome was hospital length of stay (LOS); secondary outcomes included supportive care requirements between days +4 and day +14 and time to neutrophil and platelet-20 engraftment. RESULTS: Among 176 patients evaluated in each group, median hospital LOS was 16 days, median time to neutrophil engraftment was 14 days, and median time to platelet-20 engraftment was 16 days in both groups. In addition, there were no significant differences in supportive care requirements between groups. CONCLUSION: In this study, use of gabapentin or pregabalin in combination with melphalan did not impact safety of the conditioning regimen in patients undergoing ASCT.

New and Worsening Long-term Immune-Related Adverse Events with PD-1/PD-L1 Pathway Agents in Patients with Cancer.

STUDY OBJECTIVES: Immune checkpoint inhibitors have produced durable responses across a variety of cancers. Although programmed cell death protein 1 (PD-1) and its ligand (PD-L1) inhibitors activate T cells against tumor cells, they may also cause autoimmune-like toxicities termed immune-related adverse events (irAEs). Although much is known regarding irAEs that occur early during treatment, data on the long-term toxicity profile of these agents are more limited. Our primary objective was to evaluate the frequency of patients receiving anti-PD-1/PD-L1 therapy for at least 6 continuous months who experienced new or worsening irAEs requiring clinical interventions. Secondary objectives included assessment of other factors associated with clinically significant irAEs after at least 6 months of therapy. DESIGN: Retrospective chart review. SETTING: Large university-affiliated National Cancer Institute-designated comprehensive cancer center. PATIENTS: A total of 159 adults diagnosed with any malignancy who received a PD-1/PD-L1 inhibitor-nivolumab, pembrolizumab, or atezolizumab-as monotherapy or with concurrent cytotoxic agents, for at least 6 months, between January 1, 2014, and September 1, 2017. MEASUREMENTS AND MAIN RESULTS: We collected information on the incidence and timing of irAEs, along with patient demographics and other treatment outcomes. Thirty-eight patients (24%) experienced clinically significant, new, or worsening irAEs after 6 months of treatment with anti-PD-1/PD-L1 therapy. Hypothyroidism was the most common irAE experienced (20 patients [12.6%]), followed by pneumonitis (5 patients [3%]); 2 patients died due to pneumonitis. Four patients (2.5%) had a deepened disease response beyond 6 months of treatment. CONCLUSION: Our results revealed that a significant proportion of patients continue to experience irAEs with long-term use of PD-1/PD-L1 inhibitors. These results further contribute to the risk-benefit understanding of chronic PD-1/PD-L1 antagonism and support discontinuation of these agents following deepest response.

Intrathecal Central Nervous System Prophylaxis in Patients With Diffuse Large B-cell Lymphoma at an Academic Healthcare System.

INTRODUCTION: Intrathecal chemoprophylaxis is often administered to patients with diffuse large B-cell lymphoma (DLBCL) to lower the rates of central nervous system (CNS) relapse, although its benefit has not been well-described. Prognostic models, including the CNS-International Prognostic Index (IPI), have been developed to aid in identifying patients at highest risk for CNS relapse. PATIENTS AND METHODS: We evaluated 112 patients diagnosed with DLBCL from 2009 to 2016 at Emory Healthcare and classified them as high (n = 44) or low risk (n = 68) for CNS relapse and compared CNS prophylaxis rates and relapse rates between groups. The primary outcome was to compare the CNS relapse rate in high-risk patients who received intrathecal prophylaxis with patients who did not. RESULTS: Twenty-six patients (14 high-risk and 12 low-risk) received intrathecal prophylaxis. Only 4 of 112 patients experienced a CNS relapse, including 1 in the high-risk group and 3 in the low-risk group. Among 14 high-risk patients who received intrathecal prophylaxis, no patient experienced CNS relapse compared with 1 of 30 high-risk patients without prophylaxis (P = 1.0). CONCLUSION: Given the low rates of CNS relapse in this series, it is difficult to discern the impact of current risk stratification combined with intrathecal prophylaxis on outcomes. Our observation that many high-risk patients did not receive prophylaxis, whereas many low-risk patients received prophylaxis emphasizes the need for a standardized approach.

How to Decide Which DLBCL Patients Should Receive CNS Prophylaxis.

Secondary central nervous system (CNS) relapse in aggressive non-Hodgkin lymphoma (NHL) is a dismal diagnosis with poor outcomes. While prophylaxis against secondary CNS disease is recommended in patients with highly aggressive NHLs, such as Burkitt lymphoma, patients with diffuse large B-cell lymphoma (DLBCL) present a challenging clinical dilemma due to an inherently lower risk of CNS relapse. Current guidelines suggest that prophylaxis may benefit DLBCL patients at high risk for CNS relapse; however, it has been difficult to define which patients are truly at high risk. Many studies have attempted to clarify the issue, with conflicting results. Here we review current prognostic models, risk factors, and prophylaxis methods to provide a practical approach to preventing CNS relapse in patients with DLBCL.