Healthcare Costs of Multiple Myeloma Patients with Four or More Prior Lines of Therapy, Including Triple-Class Exposure in the United States.

INTRODUCTION: The treatment of multiple myeloma (MM) remains a challenge as patients eventually progress through several lines of therapy (LOTs), requiring use of multiple MM drug classes. In this retrospective US claims-database study, we examined the healthcare costs of patients with MM who received ≥ 4 prior LOTs, including triple-class exposure (TCE). METHODS: Adult patients with MM were selected from the IBM MarketScan Commercial and Medicare claims databases (1 January 2012-30 June 2021). Eligible patients were required to have received at least four prior LOTs, and TCE (i.e., received a proteasome inhibitor, immunomodulatory drug, and anti-CD38-targeted monoclonal antibody) after the first-observed diagnosis of MM. The index date was defined as the initiation date of the first subsequent LOT after meeting the eligibility criteria for the study, and this date had to be after 1 January 2017 to capture contemporary cost estimates. The primary outcome measurements were all-cause and MM-related healthcare costs after the index date. RESULTS: The study population included 68 patients with MM (63% men), with a mean age of 59.8 years. Mean duration from first-observed MM diagnosis until index date averaged 46.7 months. During a mean follow-up of 21.9 months, total all-cause healthcare costs averaged US$757,386 per patient (equivalent to US$34,610 per patient per month). MM-related healthcare costs (US$670,561 per patient) contributed on average 88.5% to the total all-cause healthcare costs; the majority (67.2%) of MM-related healthcare costs were attributed to drug and infusion costs (US$450,952 per patient). CONCLUSIONS: In this retrospective US claims-database study, patients with MM with ≥ 4 prior LOTs, including TCE, continued to experience high healthcare costs that were mostly attributable to anti-myeloma drugs and their administration.

Healthcare Costs Incurred by Patients with Multiple Myeloma Following Triple Class Exposure (TCE) in the US.

INTRODUCTION: Multiple myeloma (MM) is a malignancy of plasma cells; most MM patients will eventually relapse or become refractory to treatment. Treating MM patients remains a challenge since patients eventually progress through several lines of therapy (LOTs), requiring the use of multiple MM drug classes. We examined healthcare resource utilization (HCRU) and the costs incurred by MM patients following triple class exposure (TCE; defined as exposure to a proteosome inhibitor, an immunomodulatory agent, and an anti-CD-38 antibody). METHODS: Adult MM patients were selected from the MarketScan® commercial and Medicare supplemental databases (January 2009-February 2021). From this cohort, patients who had TCE and ≥ 1 subsequent LOT that occurred after January 1, 2017 were included in the study population. The initiation date for the first post-TCE LOT was defined as the index date. All-cause and MM-related HCRU and the associated costs were examined post-index date. RESULTS: A total of 85 MM patients with TCE who initiated ≥ 1 subsequent LOT post-TCE and had ≥ 1 year of follow-up post-index date were included in the study population; mean age on index date was 58.8 years, and 60.0% were male. The time from first-observed MM diagnosis until index date averaged 47.5 months. During an average follow-up of 20.9 months post-index date, 64.7% of patients (N = 55) initiated a second LOT and 35.2% (N = 30) received at least 3 LOTs. During follow-up, mean total all-cause healthcare cost per patient was $722,992 (equivalent to $34,578 per patient per month [PPPM]). Approximately 90.7% ($655,524 per patient) of the total all-cause healthcare costs were MM related, 66.0% of which were MM drug/infusion costs. CONCLUSION: In this real-world US study, MM patients with TCE incurred high healthcare costs, with the majority being MM related and primarily attributed to MM drug and infusion costs.

Measuring cardiopulmonary complications of carfilzomib treatment and associated risk factors using the SEER-Medicare database.

BACKGROUND: Carfilzomib improves survival in patients with recurrent myeloma. Given the strict eligibility criteria in clinical trials, the actual frequency of cardiac adverse events (CAEs) and pulmonary adverse events (PAEs) and the risk factors associated with these AEs in the general population need to be established. METHODS: The authors extracted myeloma cases in the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database from 2000 through 2013 and corresponding claims through 2014. They then identified patients who received carfilzomib during their disease course. Subsequently, the International Classification of Diseases, Ninth Revision (ICD-9) was used to identify all the codes for CAEs, PAEs, and respiratory infections associated with carfilzomib use. Preexisting diagnoses corresponding to the CAEs and PAEs of interest were excluded to distinguish toxicity from comorbidity. Multivariate Cox regression was performed to determine those variables independently associated with the development of CAEs and PAEs. RESULTS: Of the 635 patients analyzed, the median age was 72 years (range, 36-94 years); 55% of the patients were male and 79% were white. The median duration of carfilzomib treatment was 58 days (range, 1-716 days). Overall, approximately 66% of the patients had codes for either CAEs or PAEs. In terms of CAEs, approximately 22% of patients developed hypertension, 15% developed peripheral edema, and 14% experienced heart failure. With regard to PAEs, approximately 28% of patients developed dyspnea, 15% developed cough, and 15% developed pneumonia. Only chronic obstructive pulmonary disease (COPD) was found to be independently associated with the development of CAEs. Patients with preexisting COPD were found to have a 40% increase in their hazard of developing CAEs (adjusted hazard ratio, 1.40; 95% CI, 1.03-1.90). CONCLUSIONS: In older adults with myeloma who are undergoing treatment with carfilzomib, new cardiac and pulmonary diagnoses were common. Patients with preexisting COPD were found to be at an increased risk of developing CAEs.

Metabolite Profiling and Reaction Phenotyping for the in Vitro Assessment of the Bioactivation of Bromfenac †.

Bromfenac is a nonsteroidal anti-inflammatory drug that was approved and subsequently withdrawn from the market because of reported cases of acute hepatotoxicity. Recently, in vitro studies have revealed that bromfenac requires UDPGA and alamethicin supplemented human liver microsomes (HLM) to form a major metabolite, bromfenac indolinone (BI). Bromfenac and BI form thioether adducts through a bioactivation pathway in HLM and hepatocytes. [J. P. Driscoll et al., Chem. Res. Toxicol. 2018, 31, 223-230.] Here, Cytochrome P450 (CYP) and UDP-glucuronosyltransferase (UGT) reaction phenotyping experiments using recombinant enzymes were performed on bromfenac and BI to identify the CYP and UGT enzymes responsible for bromfenac's metabolism and bioactivation. It was determined that UGT2B7 converts bromfenac to BI, and that while CYP2C8, CYP2C9, and CYP2C19 catalyze the hydroxylation of bromfenac, only CYP2C9 forms thioether adducts when incubated with NAC or GSH as trapping agents. Although CYP2C9 was shown to form a reactive intermediate, no inhibition of CYP2C9 was observed when an IC50 shift assay was performed. Reaction phenotyping experiments with BI and recombinant CYP enzymes indicated that CYPs 1A2, 2B6, 2C8, 2C9, 2C19, 2D6, and 3A4 were responsible for the formation of an aliphatic hydroxylated metabolite. An aromatic hydroxylation on the indolinone moiety was also formed by CYP1A2 and CYP3A4. The aromatic hydroxylated BI is a precursor to the quinone methide and quinone imine intermediates in the proposed bioactivation pathway. Through time-dependent inhibition (TDI) experiments, it was revealed that BI can cause an IC50 shift in CYP1A2 and CYP3A4. However, BI does not inhibit the other isoforms that were also responsible for the formation of the aliphatic hydroxylation, an alternative biotransformation that does not undergo further downstream bioactivation. The results of these metabolism studies with bromfenac and BI add to our understanding of the relationship between biotransformation, reactive intermediate generation, and a potential mechanistic link to the hepatotoxicity of this compound.

ASBMT Practice Guidelines Committee Survey on Long-Term Follow-Up Clinics for Hematopoietic Cell Transplant Survivors.

Significant advances in hematopoietic cell transplantation (HCT) have increased the long-term survivorship of its recipients, but because of unique complications arising from radiation and chemotherapy, recipients require lifelong follow-up. To evaluate current survivorship or long-term follow-up (LTFU) clinics specifically for HCT survivors and to evaluate the potential barriers in their establishment, the American Society for Blood and Marrow Transplantation (ASBMT) Practice Guidelines Committee electronically surveyed 200 HCT programs to gather quantitative and qualitative data about models of care. Among 77 programs (38.5%) that responded, 45% indicated presence of an LTFU clinic; however, LTFU care models varied with respect to services provided, specialist availability, type of patients served, and staffing. Among 55% of programs without an LTFU clinic, 100% agreed that allogeneic HCT survivors have unique needs separate from graft-versus-host disease and that complications could arise during the transition of care either from pediatric to adult settings or away from the HCT center. Lack of expertise, logistics, financial issues, and the observation that 84% of individual practitioners prefer to provide survivorship care were the identified obstacles to establishing new LTFU clinics. The ASBMT hopes that policymakers, HCT providers, and institutions will benefit from the results of this survey and recommends that delivering guidelines-driven screening and expert management of late effects is the goal of first-rate HCT survivorship care.

Clinician-educators in emerging graduate medical education systems: description, roles and perceptions.

OBJECTIVES: To describe clinician-educators (CEs) in new graduate medical education (GME) systems and characterize perception of preparedness, roles and rewards, and factors affecting job satisfaction and retention. METHODS: A cross-sectional survey of all CEs of institutions using competency-based GME and accredited by the Accreditation Council for Graduate Medical Education-International (ACGME-I). RESULTS: 274 of 359 eligible participants (76.3%) responded, representing 47 residency programs across 17 specialties. CEs were predominantly married men aged in their 40s, employed at their current institution 9.3 years (±6.4 years). CEs judged themselves competent or expert in teaching skills (91.5%), trainee assessment (82%) and mentoring (75%); less so in curriculum development (44%) and educational research skills (32%). Clinical productivity was perceived by the majority (62%) as the item most valued by their institutions, with little or no perceived value for teaching or educational efforts. Overall, 58.3% were satisfied or very satisfied with their roles, and 77% expected to remain in academic medicine for 5 years. A strong negative correlation was found between being a program or associate program director and likelihood of staying in academic medicine (aOR 0.42; 0.22 to 0.80). CONCLUSIONS: In the GME systems studied, CEs, regardless of country or programme, report working in environments that value clinical productivity over educational efforts. CEs feel competent and prepared for many aspects of their roles, have positive attitudes towards teaching, and report overall job satisfaction, with most likely to remain in academic medicine. As medical training advances internationally, the impact on and by CEs requires ongoing attention.

Use of psychosocial services increases after a social worker-mediated intervention in gynecology oncology patients.

The purpose of this study was to determine whether the introduction of psychosocial services to gynecologic oncology outpatients by a social worker increases service use. During the initial six weeks (phase I), patients were referred for psychosocial services by clinic staff. During the second six weeks (phase II), a nurse introduced available services to each patient with a brochure. During the final 12 weeks (phase III), a social worker introduced services to each patient. The authors then compared psychosocial service referral rates. The sample included 196 patients. During phase III, the probability of a patient-initiated referral increased 3.4-fold (95 percent confidence interval [CI] [1.1, 10.4], p = .04) compared with baseline; the probability of any referral rose 2.7-fold (95 percent CI [1.1, 6.3], p = .03). The mean time to referral decreased from 79.4 days at baseline to 3.9 days during phase III (p < .001). The phase III intervention was accomplished only in 34 patients (39 percent) because of scheduling conflicts. Of these, eight requested referral, resulting in a 24 percent patient-initiated referral rate after meeting with a social worker. The introduction of psychosocial services by a social worker to gynecologic oncology outpatients increases referral rates and expedites evaluation.

A history of being prescribed controlled substances and risk of drug overdose death.

OBJECTIVE: The abuse of prescription drugs has increased dramatically since 1990. Persons who overdose on such drugs frequently consume large doses and visit multiple providers. The risk of fatal overdose for different patterns of use of opioid analgesics and sedative/hypnotics has not been fully quantified. DESIGN: Matched case-control study. Cases were 300 persons who died of unintentional drug overdoses in New Mexico during 2006-2008, and controls were 5,993 patients identified through the state prescription monitoring program with matching 6-month exposure periods. OUTCOME MEASURES: Death from drug overdose or death from opioid overdose. Exposures were demographic variables and characteristics of prescription history. Crude and adjusted odds ratios (AOR) were calculated. RESULTS: Increased risk was associated with male sex (AOR 2.4, 95% confidence interval [CI] 1.8-3.1), one or more sedative/hypnotic prescriptions (AOR 3.0, CI 2.2-4.2), greater age (AOR 1.3, CI 1.2-1.4 for each 10-year increment), number of prescriptions (AOR 1.1, CI 1.1-1.1 for each additional prescription), and a prescription for buprenorphine (AOR 9.5, CI 3.0-30.0), fentanyl (AOR 3.5, CI 1.7-7.0), hydromorphone (AOR 3.3, CI 1.4-7.5), methadone (AOR 4.9, CI 2.5-9.6), or oxycodone (AOR 1.9, CI 1.4-2.6). Patients receiving a daily average of >40 morphine milligram equivalents had an OR of 12.2 (CI 9.2-16.0). CONCLUSIONS: Patients being prescribed opioid analgesics frequently or at high dosage face a substantial overdose risk. Prescription monitoring programs might be the best way for prescribers to know their patients' prescription histories and accurately assess overdose risk.

The challenge of providing infertility services to a low-income immigrant Latino population.

OBJECTIVE: To provide insight into the experience of low-income immigrant Latino couples seeking infertility treatment. DESIGN: Qualitative interview study. SETTING: Infertility clinic at a university-affiliated urban public teaching hospital. PATIENT(S): Infertile low-income immigrant Latino couples (105 women and 40 men). INTERVENTION(S): In-depth, tape-recorded interviews. MAIN OUTCOME MEASURE(S): After transcription and translation, the interviews were coded and analyzed for thematic content. RESULT(S): Four major challenges to providing infertility services to this population were identified: [1] communication: language and cultural barriers resulted in patients having difficulty both in understanding diagnoses and treatments and in communicating their questions, concerns, and experiences to physicians; [2] continuity: because medical students and residents rotated frequently, patients usually saw a different physician at each visit; [3] bureaucracy: patients reported having difficulty with appointment scheduling, follow-up visits, and timed laboratory procedures; and [4] accessibility: patients faced issues of limited availability and affordability of treatment. CONCLUSION(S): At a large, urban, university-affiliated infertility clinic, challenges related to communication, comprehension, continuity, bureaucracy, accessibility, availability, and affordability impeded the delivery of optimal infertility care to many low-income immigrant Latino patients. A greater availability of translators and both patient and physician cultural orientations to address these health care barriers is recommended.

The nephrologist as a primary care provider for the hemodialysis patient.

The role of nephrologists as de facto primary care providers (PCP) for dialysis patients is of increasing interest. We sought to determine the proportion of patients who rely on nephrologists for primary care and to identify demographic variables associated with this primary care responsibility. We reviewed the charts of 158 patients receiving hemodialysis at a suburban, freestanding, teaching hospital affiliated outpatient unit from December 1999 through January 2001. In addition, each patient was interviewed and completed a survey. Non-nephrologists were considered to be a patient's PCP if there was chart, survey or interview evidence of such a relationship. Of the 158 patients, only 56 patients had a PCP. The nephrologist thus was the de facto PCP in 65% of hemodialysis patients, a responsibility that was 3.3-fold more likely for patients not enrolled in a health maintenance organization (HMO) or managed care organization (MCO). In the non-HMO/MCO group, patients with a PCP had been on dialysis for less time than those without a PCP [2.7 vs. 4.6 years (P=0.0006)]. Only 32% of patients on dialysis <1 year had nephrologists as de facto PCP vs. 71% of those on dialysis more than 1 year (P=0.0002). This association between time on dialysis and de facto use of nephrologists as PCP was not accounted for by the shorter time on dialysis of HMO/MCO enrollees. The extent to which the nephrologist fulfills the often unsought role as PCP needs further investigation.

Correlates of initiation of injection drug use among young drug users in Baltimore, Maryland: the need for early intervention.

This article examines individual and social factors associated with initiation of illicit drug injection, with a focus on racial differences. Data were derived from across-sectional survey of young injection and noninjection drug users in Baltimore, Maryland. Participants were aged 15 to 30 and had initiated use of heroin, cocaine, and/or crack within the prior five years. Bivariate and multivariate logistic regression models were used to identify correlates of injection initiation. Of 579 drug users, 73% were injectors, 56% were male, and 41% were African American. In a multivariate model controlling for age, correlates of injection initiation were: being an African American male [Adjusted Odds Ratio (AOR): 0.08; 95% Confidence Interval (CI): 0.04, 0.17] or female (AOR = 0.12; 95%CI: 0.06, 0.27) compared to being a White male; younger age of first use of alcohol, marijuana, or inhalants (AOR=0.73; 95%CI: 0.65, 0.82); shorter time between first use of alcohol, marijuana, or inhalants and first use of heroin, crack, or cocaine (per year decrease, AOR=0.63, 95%CI: 0.40, 0.87); parental drug use (AOR=0.54, 95%CI: 0.32, 0.92); seeing someone inject prior to injection, AOR=1.96, 95%CI: 1.01, 3.50); and crack smoking (AOR=1.77, 95%CI: 1.07, 2.99). Early drug use patterns and drug exposure factors are associated with initiation injection. Interventions are needed that target noninjection drug users to prevent transition to injection drug use.