Utilization of radiation therapy in multiple myeloma: trends and changes in practice.

Plasma cell disorders including plasmacytomas and multiple myeloma (MM) are exquisitely radiosensitive, and thus, radiation therapy (XRT) is used effectively in their management. The role of XRT in the setting of novel MM therapeutics has not been explored. The 2016 National Cancer Database (NCDB) for MM with patients diagnosed between 2004 and 2013 was studied. Association between utilization of XRT as part of initial therapy and patient, disease, or treating facility characteristics was studied. A total of 111,281 cases with 91.6% MM, 7% osseous plasmacytoma (PLA-O), and 1.4% extramedullary plasmacytoma (PLA-E) were identified. XRT was utilized as part of initial therapy in 25.4% cases, including 69.3% of PLA-O, 60% of PLA-E, and 21.5% of MM patients. Patients with PLA-E and MM were significantly less likely to receive XRT as compared to PLA-O (p < 0.001). A significantly decreased use of XRT was noted over time (p < 0.001), and for advancing patient age (p < 0.001), women (p < 0.001), and blacks (p < 0.001), and with increasing income (p = 0.015). Patients with Medicare were less likely to receive XRT (OR 0.86, 95% CI 0.78, 0.94) as compared to uninsured as were those with initial treatment at academic or high-volume facilities and facilities performing stem cell transplant. There was overall decreased utilization of XRT in recent years, possibly due to advent of efficacious systemic agents for MM therapy, with a higher XRT utilization for plasmacytomas. Patterns of XRT use need to be explored prospectively, so that uniform standards of healthcare delivery can be maintained and treatment heterogeneity can be minimized.

Impact of Depression and Anxiety on Opioid Use in Hospitalized Hematopoietic Cell Transplantation Recipients.

BACKGROUND: Hematopoietic cell recipients are reported to have a high prevalence of depression and anxiety. The impact of depression and anxiety on opioid use has not been well characterized. This is of significance as the opioid epidemic continues, and over 60% of deaths secondary to drug overdose involve the use of opioids. OBJECTIVE: In this retrospective, single-center study of 275 patients who underwent hematopoietic cell transplantation (HCT) (allogeneic and autologous) for hematological malignancies, we explore the impact of depression and anxiety on opioid use. RESULTS: Patients who were both anxious and depressed at admission for HCT had increased odds of receiving an opioid (odds ratio of 4.50 [95% confidence interval: 1.75, 11.56]) compared with patients who were neither depressed nor anxious. However, patients who were either depressed or anxious did not have different odds of receiving an opioid compared with those who were neither depressed nor anxious. Autologous HCT recipients had reduced odds of receiving an opioid (odds ratio of 0.17 [95% confidence interval: 0.08, 0.38]) compared with patients undergoing allogeneic HCT. Patients with lower Karnofsky performance status (<90 on a scale of 1-100) had an increased incidence of receiving a higher Morphine milligram equivalent daily dosage (incidence rate ratio of 2.59 [95% confidence interval: 1.18, 5.67]) when modeled by zero truncated negative binomial regression. CONCLUSION: Presence of depression and anxiety impacts opioid use in patients undergoing HCT.

Timeliness of Initial Therapy in Multiple Myeloma: Trends and Factors Affecting Patient Care.

Multiple myeloma (MM) treatment has advanced significantly over the last 2 decades. In most patients, the disease course has been altered from early fatality to chronic morbidity with multiple lines of treatment. The MM treatment paradigm has shifted toward treating patients before end-organ damage occurs. Thus, timeliness of treatment initiation in this era might improve patient outcomes. This is the first report to our knowledge analyzing disparities and trends in treatment timeliness of patients with MM using the National Cancer Database. Multiple factors affected the timing of treatment initiation in MM and disparities were found. We noted that initiation of treatment was delayed in women (odds ratio [OR], 1.15; 95% CI, 1.1 to 1.2) and blacks (OR, 1.21; 95% CI, 1.14 to 1.28; reference, whites) and in patients diagnosed in more recent years (2012-2015; OR, 1.15; 95% CI, 1.1 to 1.22; reference, 2004-2007). Patients were likely to start treatment earlier if they were age ≥ 80 years (OR, 0.83; 95% CI, 0.76 to 0.9; reference, age < 60 years), were uninsured (OR, 0.81; 95% CI, 0.72 to 0.91; reference, private insurance), had Medicaid (OR, 0.87; 95% CI, 0.79 to 0.95; reference, private insurance), were treated in a comprehensive community cancer program (OR, 0.7; 95% CI, 0.65 to 0.77; reference, community cancer program), lived in a location other than the US Northeast, or had a higher Charlson comorbidity score. Patient education and income levels did not affect time to treatment initiation. Particular aspects of these disparities could be explained by our current health care system and insurance rules, whereas others need to be investigated more deeply.

Survival Trends in Young Patients With Multiple Myeloma: A Focus on Racial-Ethnic Minorities.

INTRODUCTION: Outcomes in multiple myeloma (MM) have improved significantly over time. This is true overall for all patients as well as patient subgroups based on age and race/ethnicity. Despite this, disparities are noted in outcomes when looking at racial subgroups. MATERIALS AND METHODS: We performed an analysis from the population-based Surveillance, Epidemiology, and End Results (SEER) database to evaluate improvement in relative survival rates (RSRs) for young (≤ 40 years at the time of MM diagnosis) and older (> 40 years at the time of MM diagnosis) over time by race/ethnicity, specifically focusing on Hispanic patients with MM. Expected survival was estimated using the age- and gender-specific death rates from the United States population. RSR was provided as the ratio of the observed to expected survival at individual time points. Five-year and 10-year RSRs were calculated for patients based on treatments modalities available in various time periods. RESULTS: We identified a total of 89,451 patients with MM in SEER, of which 1460 patients formed the young patients with MM (≤ 40 years) cohort. Five- and 10-year RSR improved significantly over time for all patients and older patients (> 40 years) by race (all P < .001). Evaluating the younger patients, RSR improved significantly for non-Hispanic whites and non-Hispanic blacks, but not for Hispanics. This was true for the 5-year (P = .08) and 10-year (P = .13) RSRs. CONCLUSION: We report a lack of significant benefit in long-term outcomes for younger Hispanic patients with MM over time. This could be owing to multifactorial causes that need to be addressed to mitigate outcome disparities.

Monoclonal antibody utilization characteristics in patients with multiple myeloma.

This study analyzed 91 multiple myeloma patients who received two monoclonal antibodies, Daratumumab and Elotuzumab, over a year and report the adverse event profile, infusion practices and utilization of these drugs in the real world. All current reported data on monoclonal antibodies is from clinical trials, without any real-world experience. Patients from Mayo Clinic Florida or Arizona diagnosed with relapsed or refractory multiple myeloma who were treated with Daratumumab or Elotuzumab alone or in combination between 1 January 2016 and 31 December 2016 were included in the analysis. Daratumumab-treated patients (n = 78) were more heavily pre-treated than that in published clinical trials, whereas the elotuzumab patient (n = 13) profile was similar to that published before. Infusion time was on average 2 hours less than the prescribing guidelines and premedication use varied noticeably after the initial monoclonal antibody infusion, with an overall decrease over time. We noted higher than reported haematologic adverse events, especially neutropenia and fewer non-haematologic adverse events. 91.7% infusion-related reactions were observed during the first monoclonal antibody infusion, with a subsequent decrease. All infusion-related reactions were grade 2 or less, and none of the patients discontinued treatment due to infusion-related reactions. Baseline allergy profile or laboratory tests were not associated with the likelihood of developing monoclonal antibody-related infusion-related reactions. The real-world safety profile of monoclonal antibodies showed varying adverse event patterns than those reported in previous clinical trials. The infusion-related reaction patterns were similar to previous reports. Despite changes in premedication regimens safety was maintained in succeeding infusions. Such treatment utilization data is vital to broaden our knowledge of approved therapeutic agents and maximize their benefits for patients.

Targeting CD38 Enhances the Antileukemic Activity of Ibrutinib in Chronic Lymphocytic Leukemia.

PURPOSE: CD38 has emerged as a high-impact therapeutic target in multiple myeloma, with the approval of daratumumab (anti-CD38 mAb). The clinical importance of CD38 in patients with chronic lymphocytic leukemia (CLL) has been known for over 2 decades, although it's relevance as a therapeutic target in CLL remains understudied. EXPERIMENTAL DESIGN: We investigated the biological effects and antitumor mechanisms engaged by daratumumab in primary CLL cells. Besides its known immune-effector mechanisms (antibody-dependent cell-mediated cytotoxicity, complement-dependent death, and antibody-dependent cellular phagocytosis), we also measured direct apoptotic effects of daratumumab alone or in combination with ibrutinib. In vivo antileukemic activity was assessed in a partially humanized xenograft model. The influence of CD38 on B-cell receptor (BCR) signaling was measured via immunoblotting of Lyn, Syk, BTK, PLCγ2, ERK1/2, and AKT. RESULTS: In addition to immune-effector mechanisms; daratumumab also induced direct apoptosis of primary CLL cells, which was partially dependent on FcγR cross-linking. For the first time, we demonstrated the influence of CD38 on BCR signaling where interference of CD38 downregulated Syk, BTK, PLCγ2, ERK1/2, and AKT; effects that were further enhanced by addition of ibrutinib. In comparison to single-agent treatment, the combination of ibrutinib and daratumumab resulted in significantly enhanced anti-CLL activity in vitro and significantly decreased tumor growth and prolonged survival in the in vivo CLL xenograft model. CONCLUSIONS: Overall, our data demonstrate the antitumor mechanisms of daratumumab in CLL; furthermore, we show how cotargeting BTK and CD38 lead to a robust anti-CLL effect, which has clinical implications.

First Report of Hereditary Lysozyme Amyloidosis in a South Asian Family.

Lysozyme amyloidosis (ALys) is an exceedingly rare autosomal dominant hereditary type of systemic amyloidosis that can be misdiagnosed as other common types of systemic amyloidosis. The gastrointestinal tract and the kidney are the most common sites of organ involvement. No specific treatment exists for ALys, and the management primarily consists of organ-directed supportive care. To our knowledge, this disorder has been previously reported only in European ancestries; here, we first report the occurrence of ALys in South Asian ancestry. This report highlights the need of awareness amongst physicians regarding the extension of this unique and challenging disorder to non-European ancestries.

Successful Antimicrobial Treatment of Phlegmonous Gastritis: A Case Report and Literature Review.

Phlegmonous gastritis is an uncommon acute bacterial infection of the stomach that carries a fatal prognosis in spite of the advent of antibiotics. A high index of suspicion is required in patients with risk factors. An immunocompromised state is identified as one of the most important risk factors. We hereby report a case of successful antimicrobial treatment of phlegmonous gastritis in a patient who was receiving intensive chemotherapy for acute myelogenous leukemia. We have also carried out a review of literature over the past ten years. Streptococcus pyogenes is identified as the most common causative organism, and patient presentation is usually nonspecific. Conservative treatment with prompt institution of antibiotics can lead to rapid resolution in the majority of patients.

Correlation of sociodemographic and clinical parameters with depression and distress in patients with hematologic malignancies.

A quarter of cancer patients struggle with distress or depression during their illness. Multiple organizations including the National Comprehensive Cancer Network recommend universal screening for distress and depression. Herein, we describe a universal screening program in patients with hematologic malignancies and factors associated with distress and depression. Between December 2013 and February 2015, patients with hematologic malignancies took the Patient Health Questionnaire 9 (PHQ-9) and Distress Thermometer (DT) prior to receiving their first outpatient parenteral chemotherapy. Patient demographic information as well as information regarding visit burden and baseline use of psychiatric medications were recorded. A PHQ-9 score of ≥ 9 and a DT score ≥ 4 suggested a high risk of major depression and distress. Intergroup comparisons of categorical and continuous variables were performed via chi-square and Wilcoxon rank-sum tests. Multivariate models were constructed using the stepwise selection technique using all potential variables. Two hundred forty-six patients with a median age at diagnosis 65 years (range 18-94 years) were included. In the multivariate analysis, a PHQ-9 score ≥ 9 was associated with living alone (P = 0.007), positive PHQ-2 (P = 0.003), and high Charlson comorbidity index (CCI; P = 0.02), while a DT score ≥ 4 was associated with being married (P = 0.03) and female (P = 0.03). There was no other association with high scores on either questionnaire. Patients with hematologic malignancies often have prolonged treatment and surveillance. We identified subpopulations within this group who may be at high risk of developing distress and depression and who should be aggressively screened even when universal screening programs are not available.