Patterns of prescription opioid use and opioid-related harms among adult patients with hematologic malignancies.

INTRODUCTION: Treatment advances for hematologic malignancies (HM) have dramatically improved life expectancy, necessitating greater focus on long-term cancer pain management. This study explored real-world patterns of opioid use among patients with HM. METHODS: This retrospective cohort study identified adults diagnosed with HM from January 1, 2013 through December 31, 2019 using the Truven MarketScan Commercial Claims and Encounters database. Across several HM types, we described rates of high-risk opioid use (based on Pharmacy Quality Alliance measures) and opioid-related harms, including incident opioid use disorder (OUD) diagnoses and opioid-related hospitalizations or emergency department (ED) visits. We used multivariable Cox regression to generate adjusted hazard ratios and 95% confidence intervals comparing the risk of opioid-related harms between patients with versus without high-risk opioid use. RESULTS: Our sample included 43,190 patients with HM. Median age at HM diagnosis was 54 years (interquartile range = 44-60). Most patients (61.9%) were diagnosed with lymphoma. Approximately half (49.2%) had an opioid dispensed in the follow-up period. Among all patients, 20.0% met criteria for high-risk opioid use, 0.9% had an OUD diagnosis, and 0.3% experienced an opioid-related hospitalization/ED visit in follow-up. High-risk opioid use increased the risk of an OUD diagnosis by 3.3 times (p < 0.0001) and an opioid-related hospitalization/ED visit 4.2 times (p < 0.0001). CONCLUSION: High-risk opioid use was prevalent among patients with HM and significantly increased the risk of opioid-related harms. However, rates of opioid-related harms were low. These findings highlight the importance of continually monitoring pain and opioid use throughout HM survivorship to provide safe, effective HM pain management.

Perceptions of prescription opioids among marginalized patients with hematologic malignancies in the context of the opioid epidemic: a qualitative study.

PURPOSE: Opioids are essential for treating pain in hematologic malignancies (HM), yet are heavily stigmatized in the era of the opioid epidemic. Stigma and negative attitudes towards opioids may contribute to poorly managed cancer pain. We aimed to understand patient attitudes towards opioids for HM pain management, particularly among historically marginalized populations. METHODS: We interviewed a convenience sample of 20 adult patients with HM during outpatient visits at an urban academic medical center. Semi-structured interviews were audio-recorded, transcribed, and qualitatively analyzed using the framework method. RESULTS: Among 20 participants, 12 were female and half were Black. Median age was 62 (interquartile range = 54-68). HM diagnoses included multiple myeloma (n = 10), leukemia (n = 5), lymphoma (n = 4), and myelofibrosis (n = 1). Eight themes emerged from interviews that seemed to influence HM-related pain self-management, including (1) fear of opioid-related harms, (2) opioid side effects and harms to health, (3) fatalism and stoicism, (4) perceived value of opioids for HM-related pain, (5) low perceived susceptibility to opioid-related harms and externalizing blame, (6) preferences for non-opioid pain management approaches, (7) trust in providers and opioid accessibility, and (8) external sources of pain management support and information. CONCLUSIONS: This qualitative study demonstrates that fears and stigmatized views of opioids can conflict with marginalized patients' needs to manage debilitating HM-related pain. Negative attitudes towards opioids were shaped by the opioid epidemic and reduced willingness to seek out or use analgesics. IMPLICATIONS FOR CANCER SURVIVORS: These findings help expose patient-level barriers to optimal HM pain management, revealing attitudes, and knowledge to be targeted by future pain management interventions in HM.

Bevacizumab Use and the Risk of Arterial and Venous Thromboembolism in Patients with High-Grade Gliomas: A Nested Case-Control Study.

STUDY OBJECTIVE: Bevacizumab is used in the treatment of recurrent glioblastoma, but evidence is limited on the incidence of thromboembolic complications regarding the use of this drug in real-world settings. We evaluated the risk of arterial thromboembolism (ATE) and venous thromboembolism (VTE) associated with the use of bevacizumab among adults diagnosed with high-grade gliomas in a commercially insured U.S. DESIGN: Nested case-control study. DATA SOURCE: Truven Health MarketScan Commercial and Medicare Supplemental health claims databases (2009-2015). PATIENTS: A total of 2157 patients with high-grade gliomas who underwent incident (first-time) craniotomy, radiation, and concurrent temozolomide treatment between 2009 and 2015 were identified. Overall, 25 cases of ATE and 99 cases of VTE were each identified in this cohort, and each case was matched to up to 10 controls (170 for ATE and 819 for VTE) based on sex, age, quarter year of index time, and follow-up duration by using incidence density sampling without replacement from the overall cohort. Controls were at risk for the outcome of interest (ATE or VTE) at the time of case occurrence and survived at least as long as their referent case. MEASUREMENTS AND MAIN RESULTS: Exposure to bevacizumab was determined during inpatient or outpatient encounters between the index date (date of the incident craniotomy) and the ATE or VTE event or corresponding matched control date. Multivariable conditional logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the risk of ATE and VTE separately. A higher proportion of patients with ATE received bevacizumab compared with controls (28% vs 17%; adjusted OR 1.51, 95% CI 0.54-4.24), but this excess in odds was not statistically significant. Similarly, bevacizumab was not significantly associated with VTE (13% vs 9%; adjusted OR 1.40, 95% CI 0.71-2.75). CONCLUSION: We found no significant association between the use of bevacizumab and the occurrence of thromboembolic events in patients with high-grade gliomas, although our study was limited by the small number of ATE events. Because the potential for complications from arterial thrombosis cannot be completely ruled out, further research is needed to confirm the thromboembolic safety of bevacizumab in a larger sample of patients with high-grade gliomas.

Myelodysplastic syndrome and acute myeloid leukemia after receipt of granulocyte colony-stimulating factors in older patients with non-Hodgkin lymphoma.

BACKGROUND: Granulocyte colony-stimulating factors (G-CSFs), which are used for the prevention of complications from chemotherapy-related neutropenia, are linked to the risk of developing second primary myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). The objective of this study was to examine the correlation between using a specific G-CSF agent and the risk of MDS/AML among older patients with non-Hodgkin lymphoma (NHL). METHODS: This was a retrospective cohort study of adults aged >65 years who were diagnosed with first primary NHL between 2001 and 2011. With data from the Surveillance, Epidemiology, and End Results-Medicare-linked database, adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated for the risk of MDS/AML associated with the receipt of G-CSF(filgrastim and pegfilgrastim) in Cox proportional-hazards models, which were stratified according to treatment accounting for confounding by indication. RESULTS: Among 18,245 patients with NHL patients who had a median follow-up of 3.5 years, 56% received chemotherapy and/or immunotherapy, and G-CSF was most commonly used in those who received rituximab plus multiple chemotherapy regimens (77%). Subsequent MDS/AML diagnoses were identified in 666 patients (3.7%). A modest increased risk of MDS/AML was observed with the receipt of G-CSF (HR, 1.28; 95% CI, 1.01-1.62) and a trend was observed with increasing doses (Ptrend < .01). When specific agents were analyzed, an increased risk of MDS/AML was consistently observed with filgrastim (≥10 doses: HR, 1.67; 95% CI, 1.25-2.23), but not with pegfilgrastim (≥10 + doses: HR, 1.11; 95% CI, 0.84-1.45). CONCLUSIONS: A higher of MDS/AML was observed in patients with NHL risk among those who received G-CSF that was specific to the use of filgrastim (≥10 doses), but not pegfilgrastim. Neutropenia prophylaxis is an essential component of highly effective NHL treatment regimens. The differential risk related to the types of G-CSF agents used warrants further study given their increasing use and newly available, US Food and Drug Administration-approved, biosimilar products.

Encephalopathy after high-dose Ifosfamide: a retrospective cohort study and review of the literature.

BACKGROUND: Encephalopathy occurs in 10-40% of patients treated with high-dose ifosfamide. Proposed risk factors for encephalopathy include hepatic or renal dysfunction, brain metastases, electrolyte imbalances and drug-drug interactions. OBJECTIVE: The purpose of this retrospective cohort study and literature review was to estimate the prevalence of encephalopathy, identify characteristics associated with encephalopathy and evaluate the effectiveness of methylthioninium chloride (methylene blue) in its prevention. STUDY DESIGN AND METHODS: A total of 19 patients received high-dose ifosfamide for soft tissue sarcoma during a 4-year period at our medical centre. Eight patients developed encephalopathy based on adverse drug event (ADE) reports submitted by a clinical pharmacist. These reports incorporate the Naranjo probability scale, which is used to assess the likelihood that a change in clinical status is the result of an ADE rather than the result of other factors, such as progression of disease. The demographics, concurrent medication therapy, co-existing illnesses and laboratory parameters were documented from the medical records. We also conducted a review of the literature by searching MEDLINE (1996-October 2007). MAIN OUTCOME AND RESULTS: A total of 19 patients received high-dose ifosfamide; eight patients experienced encephalopathy (group I, 42%) and 11 patients did not experience encephalopathy (group II, 58%). More women than men developed encephalopathy (group I, 87.5% vs group II, 27.3%). Serum albumin (group I, 3.1 +/- 0.3 vs group II, 3.6 +/- 0.3 g/dL), haemoglobin (10.5 +/- 1.5 vs 12.4 +/- 1.7 g/dL) and total bilirubin (0.5 +/- 0.2 vs 0.8 +/- 0.3 mg/dL) levels were substantially lower in patients with encephalopathy, whereas the ratio of actual bodyweight to the ideal bodyweight (1.4 +/- 0.3 vs 1.1 +/- 0.2) was substantially higher in these patients. Five (62.5%) patients received a subsequent cycle of high-dose ifosfamide; all of these patients received methylthioninium chloride to minimize the risk of encephalopathy. All of these patients developed encephalopathy. Other reports have found that hypoalbuminaemia is associated with encephalopathy and that methylthioninium chloride does not prevent ifosfamide-induced encephalopathy. CONCLUSIONS: In summary, female sex, low total bilirubin, albumin and haemoglobin levels, and obesity appear to be associated with ifosfamide-induced encephalopathy. Methylthioninium chloride did not appear to prevent encephalopathy with subsequent doses of high-dose ifosfamide.