Case Report Brodie's Abscess in a Patient Presenting with Sickle Cell Vasoocclusive Crisis

First described by Sir Nicholas Brodie in 1832, Brodie's abscess is a localized subacute or chronic infection of the bone, typically seen in the metaphases of long bones in children and adolescents. The diagnosis can prove to be enigmatic due to absence of clinical signs and symptoms of systemic disease. We report a very interesting case of Brodie's abscess masquerading as sickle cell vasoocclusive crisis in a 20-year-old female with sickle cell disease and review the literature

Clinical Outcomes in Relapsed/Refractory Multiple Myeloma Patients Receiving Sequential Elotuzumab and Daratumumab: A Single Center Experience

Daratumumab and elotuzumab are monoclonal antibodies approved by the FDA in November 2015 for the treatment of relapsed/refractory multiple myeloma (RRMM). Daratumumab was approved as a single therapy targeting plasma cell surface CD38, while elotuzumab was approved as part of combination therapy (with lenalidomide), targeting SLAMF7 to impact natural killer cell activation. While both therapies are involved in the recruitment of cellular cytotoxic mechanisms against multiple myeloma, the efficacy of each after a patient has relapsed on the other therapy is unclear. We conducted a retrospective analysis of 26 patients with RRMM at the University of Miami Sylvester Comprehensive Cancer Center that received both elotuzumab and daratumumab between January 2016 and December 2018 to determine if progression-free survival (PFS) with each monoclonal antibody is affected by previous treatment with the other. Median age at time of treatment was 59.7 years, and 58% of patients were female. Median number of treatments prior to first monoclonal antibody was 4, and median time to first monoclonal antibody was 58 months. Seventeen patients received daratumumab prior to elotuzumab, while nine patients received elotuzumab prior to daratumumab. Patients that received daratumumab first received on average 2 treatments before receiving elotuzumab, while patients receiving elotuzumab first received 1 treatment on average before receiving daratumumab, and time between treatments was significantly shorter for patients receiving daratumumab first (3.7 months vs. 12.4 months, p = 0.0009). Overall survival (OS) and cumulative PFS trended higher in patients receiving elotuzumab first but did not reach significance (OS 37 months vs. 21.7 months, p = 0.07, and PFS 15.5 months vs. 7.6 months, p = 0.09). PFS with initial elotuzumab was higher than with initial daratumumab (11.9 months vs. 3.5 months, p = 0.0124). PFS on daratumumab trended favorably when elotuzumab was administered first (9.4 months vs. 3.0 months), although not significant (p = 0.19). In patients receiving daratumumab, 47% initially demonstrated response, all with eventual progression, with 40% responding to later elotuzumab therapy. Conversely, 56% of patients receiving elotuzumab first demonstrated a response, with 44% eventually progressing over time, and 56% responding to subsequent daratumumab therapy. These results generate a plausible hypothesis related to a possible potentiating effect of elotuzumab that extends after therapy regimen has changed and warrants further investigation into the sequencing of these two therapies in RRMM and the interplay of their different immunologic impact. Disclosures Hoffman: Seattle Genetics: Research Funding; Loxo: Current equity holder in publicly-traded company; Celgene: Honoraria, Speakers Bureau

Brodie’s Abscess in a Patient Presenting with Sickle Cell Vasoocclusive Crisis

First described by Sir Nicholas Brodie in 1832, Brodie’s abscess is a localized subacute or chronic infection of the bone, typically seen in the metaphases of long bones in children and adolescents. The diagnosis can prove to be enigmatic due to absence of clinical signs and symptoms of systemic disease. We report a very interesting case of Brodie’s abscess masquerading as sickle cell vasoocclusive crisis in a 20-year-old female with sickle cell disease and review the literature

Prevalence of targetable mutations in black patients with lung cancer: A systematic review and meta-analysis

e13105 Background: Although poorer outcomes of lung cancer in Blacks compared to other racial groups has been strongly linked to socio-economic factors, it is important to investigate whether lower prevalence of targetable mutations limit treatment options, thereby also contributing to worse outcomes. This study examines the prevalence of EGFR, ALK, ROS-1 and BRAF lung cancer mutations in Blacks compared to other races. Methods: We conducted a meta- analysis compliant with PRISMA guidelines. Searched databases included PubMed/MEDLINE, Cochrane CENTRAL, EMBASE, Google Scholar and clinicaltrials.gov. Publication bias was mitigated by searching clinicaltrials.gov for unpublished studies. Searches were run to 11/19/2018. Two rounds of screening were performed based on title and then abstract by two independent reviewers. For the purposes of this study we defined racial groups as Black, Asian, Hispanic, and White/Caucasian. We selected studies of lung cancer patients (any stage or type) where the prevalence of at least one mutation was reported in Blacks. We calculated the pooled prevalence of mutations by racial group using fixed effects, exact binomial distributions and Freeman-Turkey double arcsine transformation to stabilize the variances. Results: Prevalence % of mutations by race reported with 95% Confidence Interval in parentheses N = number of tests performed We included 20 studies which totaled 11,867 lung cancer patients. Each mutation tested on a tissue sample was considered an event, for a total of 15,306 events. EGFR was the most prevalent mutation in Blacks (6%). Compared to other races Blacks had the lowest prevalence of all four mutations. Conclusions: In the era of targeted therapy, outcomes for metastatic lung have improved significantly. Of concern, our results show that Blacks are disproportionately ineligible for these therapies due to lower prevalence of targetable mutations. More research is needed to evaluate the unique tumor characteristics and therapeutic strategies in this sub group of patients, in the hope of achieving better disease outcomes.[Table: see text

Pulmonary Kaposi Sarcoma: An Uncommon Cause of Respiratory Failure in the Era of Highly Active Antiretroviral Therapy—Case Report and Review of the Literature

Kaposi Sarcoma (KS) is the most common malignancy associated with Acquired Immune Deficiency Syndrome (AIDS) and is caused by Human Herpesvirus 8 (HHV 8) or Kaposi Sarcoma Herpesvirus (KSHV). In about 90% of cases Kaposi Sarcoma is associated with cutaneous lesions; however visceral disease can occur in the absence of cutaneous involvement. In the era of Highly Active Antiretroviral Therapy (HAART), the incidence of KS has declined. Clinical features of pulmonary KS might be difficult to distinguish from pneumonia in the immunocompromised patients and could lead to diagnostic challenges. First-line treatment of KS is with HAART and the incidence has declined with its use. Systemic chemotherapy may play a role depending on the extent of the disease. We report the case of a young man who presented with pulmonary symptoms and was later found to have pulmonary KS. Interestingly this diagnosis was made in the absence of the classic skin lesions. His disease was complicated by progressive respiratory failure and he eventually died

Plasma Cell Leukemia Presenting as a Chest Wall Mass: A Case Report

Plasma cell leukemia (PCL) is an uncommon neoplasm of plasma cells, with an aggressive clinical course and poor outcome, even with current standard of care. It can occur either de novo (primary PCL) or as a progression of multiple myeloma (MM). This disease has unique diagnostic criteria but certain genetic markers and clinical features may overlap with MM. Due to the low prevalence of PCL, guidelines on its management are extrapolated from the management of MM and based on small retrospective studies and cases reports/series. We present an interesting case of PCL in a middle-aged African-American male, who was diagnosed incidentally after chest wall imaging for an unrelated complaint. The diagnostic approach, management and outcomes of PCL are discussed

Hypogammaglobulinemia and Its Implications in Patients Treated with Daratumumab: A Single Institution Experience

Introduction: Daratumumab is an IgG Kappa monoclonal antibody (mAB) to CD38, a surface glycoprotein expressed on plasma cells. It was approved in 2015 as monotherapy for Multiple Myeloma (MM) patients who failed three prior lines of therapy. Its approval was then expanded to second line and most recently first line. As such, patients are now getting earlier and longer exposure to this mAB. Disease response to daratumumab is monitored by demonstrating a fall in paraprotein levels. It is becoming widely appreciated that hypogammaglobulinemia (HGGE) ie. (IgG<600mg/dl) with risk of infection, is a potential complication for patients on daratumumab. The immune mediated attack by daratumumab on CD38 expressing plasma cells also results in destruction of normal lymphocytes, resulting in impaired production of polyclonal immunoglobulins and diminished immunity. We aim to explore the incidence, severity and clinical significance of HGGE in patients on daratumumab. Methods: We conducted a retrospective chart review of all patients treated with daratumumab as single agent or in combination (November 2015-June 2019), who had documented baseline and post therapy quantitative IgG levels. Demographics, subtype of plasma cell disease, bone marrow cytogenetics/FISH, serial IgG levels, incidence of significant infections and need for IVIG therapy were collected as part of this exploratory data analysis. Results: Among 145 eligible patients, 53% were male, 37% Hispanic, 19% Black/African American and 72% were age<70 at diagnosis. The majority of patients had an IgG paraprotein (56.6%), followed by IgA (18.6%), Free Kappa only (13.1%) and Free Lambda only (9.7%). Hispanics were more likely to have high risk cytogenetics (OR=2.29, p=0.0804). 34.5% of patients had previous autologous stem cell transplant. At baseline 30.3% of all patients had HGGE; 58.1% non-IgG patients and only 9.6% IgG patients. The mean baseline IgG level in IgG patients was 1986.1 mg/dl and for non-IgG patients was 698.1 mg/dl. After being treated with daratumumab, 61.4 % of all patients developed HGGE; 42.2% of IgG patients and 87.1% of non-IgG patients. The mean Nadir IgG level for the IgG subtype cohort was 643.7 mg/dl and for the non-IgG cohort was 355.9 mg/dl. The incidence of significant infection in total group was 23.4% (21.7% in IgG vs 25.8% in non-IgG). Bacterial pneumonia and sepsis were the two most common infections. Despite the relatively high incidence of HGGE in this cohort, only 11 were treated with IVIG. (5 IgG vs 6 non-IgG). Using a univariate logistic regression model, Black/ African Americans and patients with higher baseline IgG were less likely, but non-IgG patients were more likely to develop HGGE (all p<0.05) . Conclusion: Our study identifies a high incidence of meaningful HGGE in patients on daratumumab. In the non-IgG subtype, the relationship is straightforward, as any drop in IgG reflects a drop in polyclonal immunoglobulins and impaired humoral immunity. In contrast, in the IgG subtype, a fall in IgG levels has two components; a fall in the monoclonal protein (indicative of favorable disease response) as well as a fall in polyclonal IgG. There was a lower incidence of pre and post treatment HGGE in the IgG cohort compared to the non-IgG cohort( ie.IgA, IgD, Free Kappa and Free Lambda). In contrast the incidence of infection in both cohorts were very similar. This suggests that polyclonal HGGE in IgG subtype plasma cell disorders may be largely undetected and undertreated, due to apparently normal IgG levels caused by pathologic production of monoclonal IgG. When we attempt to subtract the monoclonal element (m-spike in the serum protein electrophoresis) from the total IgG, the magnitude of hypogammaglobulinemia in the IgG cohort approximates that of the non-IgG group. Given that daratumumab adds a small amount to the measured m-spike, further techniques to quantify true polyclonal IgG levels in the IgG cohort are needed. The incidence and depth of HGGE associated with daratumumab has not been previously well quantified. Our study demonstrates that the incidence of HGGE doubled after therapy with daratumumab (30.3% vs 61.4%). This data will sensitize physicians and possibly lead to generation of guidelines for closer monitoring of IgG, use of IVIG and other precautions in patients on daratumumab. In our own institution, we anticipate the detection of HGGE and use of IVIG in these patients to increase substantially. Disclosures Hoffman: Celgene: Speakers Bureau

Prevalence of Targetable Mutations in Black Patients With Lung Cancer: A Systematic Review and Meta-Analysis

PURPOSE: Inferior outcomes of Black patients with lung cancer compared with other racial groups are often linked to socioeconomic factors. It is crucial to determine whether a varying prevalence of targetable mutations limits treatments and contributes to disparities. MATERIALS AND METHODS: We conducted a meta-analysis on the prevalence of lung cancer EGFR, ALK, ROS-1, and BRAF mutations in Black patients compared with White, Hispanic, and Asian patients. We searched PubMed/MEDLINE, Cochrane Library, EMBASE, CENTRAL, Google Scholar, and clinicaltrials.gov databases. We selected studies reporting the prevalence of at least one mutation in the Black population. We calculated the pooled prevalence of mutations using fixed effects, exact binomial distributions, and Freeman-Turkey double arcsine transformation to stabilize the variances. RESULTS: Twenty studies with 11,867 patients were included. In Black patients, EGFR was the most prevalent mutation (6%; 95% CI, 5 to 7), followed by BRAF (1%; 95% CI, 0 to 2), ALK (1%; 95% CI, 0 to 2), and ROS-1 (0%; 95% CI, 0 to 1). Black patients had a lower prevalence of EGFR mutations than White, Hispanic, and Asian patients ( P < .01). BRAF mutations were less prevalent in Black compared with White patients ( P < .05), and ALK mutations were less prevalent when compared with Hispanic patients ( P < .05). CONCLUSION: EGFR is the most frequent mutation found in Black patients, although its prevalence is lower than that in other races. Black patients have a low overall prevalence of ALK, ROS-1, and BRAF mutations. Given that disproportional eligibility for targeted therapies may be contributing to inferior outcomes, research focused on the Black population is needed to evaluate specific tumor characteristics and therapeutic strategies