Nivolumab is a standard treatment option in several advanced malignancies, but safety and efficacy are still unknown in patients with human immunodeficiency virus (HIV) infection. We describe a case series of people living with HIV (PLWH) receiving nivolumab in the Veterans Health Administration (VA) and report responses and toxicities. We identified all PLWH who received nivolumab at any VA facility since 2000 in the Corporate Data Warehouse (CDW), which provides nationwide research access to VA electronic medical records. We identified 16 HIV-infected nivolumab recipients. The median number of nivolumab doses received was 6 (range, 1–32). Changes in CD4 count during therapy were variable, with 70% (7/10) of patients experiencing increases. Half of PLWH were treated for non–small-cell lung cancer; 2 for Hodgkin lymphoma (HL), 2 for renal cell carcinoma, and 4 for off-label cancers. For non–small-cell lung cancer, 7 patients had evaluable responses. Although 5 of 7 patients immediately progressed, 1 had a partial response and 1 had stable disease, which were both durable. Two of 16 (14%) PLWH had complete responses; both with HL (2/2 HL, 100%). The prevalence of immune-related adverse effects was 40% overall (6/15); 27% (4/15) had pneumonitis. To our knowledge, this is the largest case series reporting outcomes with nivolumab in PLWH. Outcomes were comparable with those seen in studies of HIV-uninfected patients, and particularly interesting for HL. The reason for the high proportions of immune-related adverse effects is unclear, but needs to be confirmed in larger studies.
Abstract BACKGROUND: In multiple myeloma (MM), the presence of TP53 deletion is associated with poor prognosis. It is found in roughly 10% of newly diagnosed patients. Lower incidence of TP53 deletion is reported in African American (AA) compared to Caucasian (CA), suggesting a possible contribution of disease biology to clinical disparity in AA. Our recent report of a significantly superior age-adjusted risk of death in AA compared to CA patients in the Veteran population also suggests possible racial differences in disease biology. Here we investigated the incidence of TP53 deletion among younger (<65) versus older AA and CA patients with MM at the VA. METHODS: We identified 15717 patients with MM from 1999 to 2017 using the VA’s nationwide Corporate Data Warehouse. We extracted data on patients’ age, race, and ISS stage, as well as data on their therapy at induction and stem-cell transplant (SCT). Additionally, we extracted data on TP53 deletion testing and results using a natural language processing algorithm and focused our analysis on patients with these data. RESULTS: We identified 5,744 MM patients evaluated for TP53 deletion by conventional cytogenetics and/or FISH, including 32.5% AA (1,864) and 67.5% CA (3,880) patients. Greater proportion of AA patients (53%) were younger (<65 years), compared to CA (39%; p<0.001). Overall, among those tested, TP53 deletion was reported in 9.6% of patients, but the incidence was significantly lower in AA (7.2%) compared to CA (10.7%; p<0.001). Among patients <65 years of age, difference in incidence of TP53 deletion between AA and CA was 3.2% (8.1% vs 11.3%; p=0.01), while in those ≥65 years age, it was 4.1% (6.4% vs 10.5%; p=0.0005), suggesting increased difference in the incidence of TP53 deletion with age. The rates of TP53 deletion across different ISS stages were not significantly different, nor did ISS stage differ across race. The majority of patients with TP53 deletion (95.2%) received either proteasome inhibitor or immunomodulator at induction, but only 24.7% were treated with the combination, and only 21.4% proceeded to SCT. Median survival among younger patients with TP53 deletion appeared substantially lower in AA than in CA (5.1 vs 7.0 years; p=0.74), though without reaching significance, perhaps due to sample size. In contrast, younger AA without TP53 deletion had a significantly longer median survival than CA (8.0 vs 6.2 years; p<0.01). Among older patients, AA had longer median survival regardless of TP53 deletion status. CONCLUSIONS: This large cohort study identified significantly lower incidence of TP53 deletion in AA compared to CA. Yet, when present in younger AA patients, TP53 deletion correlated with worse survival. These results identify racial disparity in both occurrence and impact of TP53 deletion and now suggests the need for a more comprehensive genetic assessment to develop risk stratification in AA myeloma patients. Citation Format: Diana Cirstea, Nathanael Fillmore, Hassan Yameen, Sarvari Yellapragada, Chizoba Ifeorah, Nhan Do, Mary Brophy, Nikhil Munshi. Racial differences in incidence and impact of TP53 deletion on outcome in African American and Caucasian veterans with multiple myeloma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1569.
Key Points Vitamin D deficiency is a predictor for poor overall survival in patients with multiple myeloma, even after adjusting for age and stage. This difference is only observed in white patients, not African Americans, even under a lower threshold for deficiency.
Gelatinous marrow transformation (GMT) is a rare condition observed in severe illness or malnutrition, in which the bone marrow contains amorphous "gelatinous" extracellular material, and histopathology demonstrates varied degrees of fat cell atrophy and loss of hematopoietic elements. An association of GMT with imatinib use in chronic myeloid leukemia (CML) has been reported recently. The objective of this study is to describe a case of GMT associated with imatinib use and review the existing similar cases in the literature to identify epidemiological patterns and potential imatinib-induced mechanisms leading to gelatinous conversion.
8033 Background: The majority of older adults carry two or more chronic conditions (multimorbidity). Although comorbidity in multiple myeloma (MM) has often been described with comorbidity counts, the impact of multimorbidity clusters has yet to be investigated. Methods: In a national cohort of 7815 patients aged ≥60 years diagnosed with and treated for MM in Veterans Affairs Healthcare System, we extracted 53 chronic conditions from claims in the 3 years preceding diagnosis using the Centers of Medicare and Medicaid Services-defined chronic and disabling conditions. We performed latent class analysis to identify patterns of multimorbidity that coexisted with MM at diagnosis. We then assessed whether these multimorbidity patterns were associated with survival in 5992 non-transplanted patients initially treated with either doublet or triplet chemotherapy regimens, adjusting for MM stage, sociodemographic factors, and prognostic lab values. Results: Mean follow up time was 3.1 years (SD, 2.6). We identified 6 multimorbidity clusters at the time of MM diagnosis: minimal disease (1302 patients, 16.7%), cardiovascular disease (2011, 25.7%), diabetes and complications (1820, 23.3%), psychiatric and substance use disorders (931, 11.9%), chronic lung disease (759, 9.7%), and multisystem impairment (992, 12.7%). In patients initially treated with doublet or triplet chemotherapy, survival varied across multimorbidity patterns (p < 0.001); patients with minimal disease had the best survival (median survival [MS] = 4.5 years, 5-year survival = 47.5%), and patients with multisystem impairment had the worst (MS = 2.4 years, 5-year survival = 24.3%). After adjustment for covariates, patients with clusters of chronic lung disease (HR = 1.40 [1.22-1.60]), psychiatric and substance use (HR = 1.57 [1.37-1.79]), and multisystem impairment (HR = 1.71 [1.50-1.94]) had higher hazards of death than patients with minimal disease. Conclusions: We found higher-impact and lower-impact multimorbidity clusters among older veterans with newly-diagnosed MM treated with chemotherapy. Unique combinations of chronic diseases may interact with MM itself to drive differences in mortality.
