Development and validation of algorithms for identifying lines of therapy in multiple myeloma using real-world data.

Aim: To validate algorithms based on electronic health data to identify composition of lines of therapy (LOT) in multiple myeloma (MM). Materials & methods: This study used available electronic health data for selected adults within Henry Ford Health (Michigan, USA) newly diagnosed with MM in 2006-2017. Algorithm performance in this population was verified via chart review. As with prior oncology studies, good performance was defined as positive predictive value (PPV) ≥75%. Results: Accuracy for identifying LOT1 (N = 133) was 85.0%. For the most frequent regimens, accuracy was 92.5-97.7%, PPV 80.6-93.8%, sensitivity 88.2-89.3% and specificity 94.3-99.1%. Algorithm performance decreased in subsequent LOTs, with decreasing sample sizes. Only 19.5% of patients received maintenance therapy during LOT1. Accuracy for identifying maintenance therapy was 85.7%; PPV for the most common maintenance therapy was 73.3%. Conclusion: Algorithms performed well in identifying LOT1 - especially more commonly used regimens - and slightly less well in identifying maintenance therapy therein.

Electronic health data helps us understand treatment in the 'real world'. The data has great value in cancer if we can identify the drugs patients get. Yet this is hard in multiple myeloma (MM), where treatment is complex. Algorithms (set of decision rules) to identify drugs can help here. We tested an existing algorithm for identifying 'lines of therapy' (LOT) given to patients with MM. Each LOT included one or more drugs for MM. We also developed and tested a new algorithm for 'maintenance therapy'. This is a treatment given to help maintain the response to the main MM treatment. We tested how well the algorithms identified MM treatments in electronic health data. This data came from Henry Ford Health, a healthcare system in Michigan, USA. Treatments were confirmed by cancer specialists who reviewed medical charts. The LOT algorithm was good at finding the first LOT patients. The maintenance algorithm did a fair job of identifying the most used therapy. Our algorithms could help researchers study the real-world treatment of MM.

Real-world comparative effectiveness of triplets containing bortezomib (B), carfilzomib (C), daratumumab (D), or ixazomib (I) in relapsed/refractory multiple myeloma (RRMM) in the US.

Multiple available combinations of proteasome inhibitors, immunomodulators (IMIDs), and monoclonal antibodies are shifting the relapsed/refractory multiple myeloma (RRMM) treatment landscape. Lack of head-to-head trials of triplet regimens highlights the need for real-world (RW) evidence. We conducted an RW comparative effectiveness analysis of bortezomib (V), carfilzomib (K), ixazomib (I), and daratumumab (D) combined with either lenalidomide or pomalidomide plus dexamethasone (Rd or Pd) in RRMM. A retrospective cohort of patients initiating triplet regimens in line of therapy (LOT) ≥ 2 on/after 1/1/2014 was followed between 1/2007 and 3/2018 in Optum's deidentified US electronic health records database. Time to next treatment (TTNT) was estimated using Kaplan-Meier methods; regimens were compared using covariate-adjusted Cox proportional hazard models. Seven hundred forty-one patients (820 patient LOTs) with an Rd backbone (VRd, n = 349; KRd, n = 218; DRd, n = 99; IRd, n = 154) and 348 patients (392 patient LOTs) with a Pd backbone (VPd, n = 52; KPd, n = 146; DPd, n = 149; IPd, n = 45) in LOTs ≥2 were identified. More patients ≥75 years received IRd (39.6%), IPd (37.8%), and VRd (36.7%) than other triplets. More patients receiving VRd/VPd were in LOT2 vs other triplets. Unadjusted median TTNT in LOT ≥ 2: VRd, 13.9; KRd, 8.7; IRd, 11.4; DRd, not estimable (NE); and VPd, 12.0; KPd, 6.7; IPd, 9.5 months; DPd, NE. In covariate-adjusted analysis, only KRd vs DRd was associated with a significantly higher risk of next LOT initiation/death (HR 1.72; P = 0.0142); no Pd triplet was significantly different vs DPd in LOT ≥ 2. Our data highlight important efficacy/effectiveness gaps between results observed in phase 3 clinical trials and those realized in the RW.

Treatment patterns and outcomes among nontransplant newly diagnosed multiple myeloma patients in Spain.

Aim: To describe treatment patterns and outcomes in nontransplant newly diagnosed multiple myeloma (NDMM) patients in Spain. Methods: This retrospective study included two cohorts of NDMM patients diagnosed between 1 January 2012 to 31 December 2013 and 1 April 2016 to 31 March 2017. Results: Among 113 patients, proteasome inhibitor (PI) + alkylator combinations (49%) and PI-based regimens without an alkylator (30%) were the most common first-line (1L) therapies. Use of PI + immunomodulatory drug-based regimens increased between the cohorts; PI-based regimens without an alkylator/immunomodulatory drug decreased. Use of 1L oral regimens was low but increased over time; use of maintenance therapy was low across both periods. Median 1L duration of treatment was 6.9 months. Conclusion: Short 1L duration of treatment and low use of 1L oral regimens and maintenance therapy highlight unmet needs in NDMM.

Lay abstract This study describes treatment patterns and outcomes in newly diagnosed multiple myeloma (NDMM) patients in Spain who were not candidates for transplant. The study looked at two patient groups: patients diagnosed between 1 January 2012 and 31 December 2013 and those diagnosed between 1 April 2016 and 31 March 2017. Among the 113 patients considered, the most common first-line therapies were proteasome inhibitor (PI) + alkylator combinations (49%) and PI-based regimens without an alkylator (30%). We saw increased use of PI with immunomodulators (which arm the immune system to battle disease) and decreased use of PI-based regimens without an alkylator or immunomodulator. First-line use of oral regimens was low but increased over time. The median length of first-line treatment for both groups combined was 6.9 months. Finding low use of first-line oral regimens and maintenance therapy and a short duration of first-line treatment, our study highlights the unmet needs that exist in NDMM patients who are not transplant candidates in Spain.

Real-world treatment patterns and outcomes in non-transplant newly diagnosed multiple Myeloma in France, Germany, Italy, and the United Kingdom.

OBJECTIVES: The treatment paradigm in newly diagnosed multiple myeloma (NDMM) is evolving toward individualized, risk-directed, and longer duration of therapy (DOT). The objective of this study was to describe treatment patterns and outcomes in non-transplant NDMM in four European countries. METHODS: This retrospective chart review included adults with NDMM diagnosed between January 1, 2012, and December 31, 2013 (early cohort), or April 1, 2016, and March 31, 2017 (recent cohort). RESULTS: Among 836 patients, molecular testing was performed in 21% and 35% patients of early vs recent cohorts; proteasome inhibitor (PI)/alkylator combinations were the principal first-line (1 L) therapy (39% vs 43%). Use of immunomodulatory drug (IMID)/alkylator combinations declined from early to recent cohort (26% vs 13%) but IMID (7% vs 16%) use increased. Few patients (5%) received 1 L maintenance therapy. Two-thirds of patients were treated with a fixed duration intent, with a median 7-month 1 L DOT and progression-free survival (PFS) of 32.8 months in the early cohort. Both 1 L DOT and PFS were longer with oral compared to injectable regimens. CONCLUSIONS: Although frontline treatment patterns changed significantly, 1 L DOT is short. The uptake of molecular testing and 1 L maintenance is low. These results highlight areas of unmet need in NDMM.

Quality of life is maintained with ixazomib maintenance in post-transplant newly diagnosed multiple myeloma: The TOURMALINE-MM3 trial.

OBJECTIVES: Health-related quality of life (HRQoL) is particularly important during maintenance therapy (MT) in newly diagnosed multiple myeloma post-transplant, when disease symptoms are limited. METHODS: We assessed HRQoL in patients randomised to 26 cycles of MT (ixazomib vs placebo) in TOURMALINE-MM3 (NCT02181413). RESULTS: The characteristics at study entry were well-balanced between ixazomib (n = 386) and placebo (n = 251) arms. At study entry, EORTC QLQ-C30 and MY20 scores were high for functional scales and low for symptom scales and were comparable with those of the general population. Changes in subscale scores across intervals, analysed over 30 four-week intervals using a linear mixed-effects model, were generally small and similar between arms for the EORTC QLQ-C30 Global Health Status/QoL, Physical Functioning, and Pain subscales and EORTC QLQ-MY20 Disease Symptoms subscale and Peripheral Neuropathy item. EORTC QLQ-C30 Nausea/Vomiting and Diarrhoea subscales were consistently worse for ixazomib than for placebo, in line with the ixazomib toxicity profile. Even when least-squares mean differences between arms were statistically significant, none reached the established minimal important clinical difference of 10 in multiple myeloma. CONCLUSIONS: In addition to improvement in progression-free survival with ixazomib, HRQoL was maintained in both arms. Active treatment with ixazomib did not have an adverse impact on HRQoL.

Patient-Reported Factors in Treatment Satisfaction in Patients with Relapsed/Refractory Multiple Myeloma (RRMM).

BACKGROUND: Therapy choices in relapsed/refractory multiple myeloma (RRMM) should consider patient satisfaction with treatment, because it is associated with adherence to therapy, health outcomes, and medical safety. The primary objective of this pilot cross-sectional observational study was to ascertain factors associated with patient-reported treatment satisfaction in RRMM. PATIENTS AND METHODS: Patients with a self-reported diagnosis of RRMM recruited from PatientsLikeMe, MyelomaCrowd, and Facebook were administered an electronic survey that included questions on demographics and clinical history, treatment experience, economic burden, and standardized patient-reported outcome measures, including the Treatment Satisfaction Questionnaire for Medication, Eastern Cooperative Oncology Group performance status (ECOG PS) measure, and Work Productivity and Activity Impairment Questionnaire: Specific Health Problem V2.0. Univariable and multivariable analyses were used to identify predictors of patient-perceived treatment satisfaction. RESULTS: One hundred sixty patients with RRMM participated in the study, with a median of two prior relapses and 66.3% reporting the most recent relapse within the last 12 months. ECOG PS ≥2 was associated with lower patient-reported global satisfaction and perceived effectiveness of current treatment. In addition to shorter time spent receiving therapy, orally administered treatment was the strongest predictor of higher satisfaction with treatment convenience. For patients receiving an injectable drug-containing regimen versus an all-oral regimen, respectively, time spent receiving multiple myeloma-directed therapy was higher (12.6 vs. 4.0 hours per month), and total monthly indirect costs were $1,033 and $241. CONCLUSION: Poor ECOG PS was linked to reduced treatment satisfaction and perceived effectiveness of current therapy, whereas an all-oral regimen was associated with increased treatment convenience satisfaction. IMPLICATIONS FOR PRACTICE: This study suggests that attributes including better Eastern Cooperative Oncology Group performance status, less time spent receiving treatment, and oral route of treatment administration lead to higher patient-perceived satisfaction with relapsed/refractory multiple myeloma (RRMM) treatment. Oral route of administration was also associated with less time spent receiving treatment and reduced economic burden for patients. Increased attention to these factors in shared treatment decision making is warranted to help identify individual patient needs, preferences, and expectations for RRMM treatments, to resolve dissatisfaction issues, and to improve the experience of patients with RRMM.

INSIGHT MM: a large, global, prospective, non-interventional, real-world study of patients with multiple myeloma.

With the introduction of new drugs with different mechanisms of action, multiple myeloma (MM) patients' outcomes have improved. However, the efficacy seen in clinical trials is often not seen in real-world settings and data on the effectiveness of MM therapies are needed. INSIGHT MM is a prospective, global, non-interventional, observational study that is enrolling approximately 4200 patients with newly diagnosed or relapsed/refractory MM, making it the largest study of its kind to date. The study aims to describe contemporary, real-world patterns of patient characteristics, clinical disease presentation, therapies chosen, clinical outcomes (response, treatment duration, time-to-next-therapy, progression-free and overall survival), safety, healthcare resource utilization and quality of life. One interim analysis has been conducted to date; current accrual is approximately 3094 patients. Trial registration number: NCT02761187.

Evaluating meaningful changes in physical functioning and cognitive declines in metachromatic leukodystrophy: a caregiver interview study.

BACKGROUND: Metachromatic leukodystrophy (MLD) is a rare lysosomal storage disease caused by deficient activity of arylsulfatase A (ASA). Treatment options for patients are limited; gene therapy based on haematopoietic stem cell transplantation is the only approved treatment for some subtypes of MLD. Any therapeutic benefit of treatments must be meaningful for patients and their families. We evaluated the clinical meaningfulness of slowing the decline in gross motor function as measured by the Gross Motor Function Classification in MLD (GMFC-MLD) from the caregiver perspective via semi-structured telephone interviews with caregivers of children with late-infantile MLD. We also evaluated the perceived significance of declines in communication abilities measured by the Expressive Language Function Classification in MLD (ELFC-MLD). This work could help to inform the endpoints of a phase 2 clinical trial (NCT03771898) assessing the efficacy of intrathecal recombinant human ASA in MLD. RESULTS: Twelve caregivers were recruited, reporting on 12 children with MLD. Children had a mean age of 6.1 years; mean age at symptom onset was 17.6 months. Most children (10/12) progressed from walking without support (categories 0-1) to a loss of locomotion (categories 5-6) in ≤ 2 years. Caregivers felt that GMFC-MLD and ELFC-MLD accurately described motor and language declines in their children, respectively. Most caregivers (10/12) reported that the idea of delaying disease progression would be meaningful. Further, a slowing of motor function decline in GMFC-MLD, from category 1 to category 3 or from category 2 to category 4 over 2 years, was seen as meaningful by all caregivers asked; however, only 3/12 caregivers reported that delayed decline would be meaningful if baseline category was ≥ 3. Caregivers also reported that delaying expressive language decline at any level that did not indicate a complete loss of expressive language (indicated by categories 1-3) would be meaningful. CONCLUSIONS: Caregivers of children with MLD felt that a delayed decline in gross motor function, as assessed by the GMFC-MLD, would be meaningful, supporting the selection of primary and secondary endpoints for the phase 2 clinical trial. Communication abilities were another area of significance for consideration in future clinical trial design.

Network meta-analysis for indirect comparison of lanadelumab and berotralstat for the treatment of hereditary angioedema.

Aim: With no head-to-head studies comparing the effectiveness of lanadelumab and berotralstat for prevention of hereditary angioedema (HAE) attacks, this network meta-analysis (NMA) aimed to indirectly compare the effectiveness of these treatments. Materials & methods: The NMA, using the published data from Phase III trials, was performed using a frequentist weighted regression-based approach following Rücker et al. Efficacy outcomes of interest were HAE attack rate per 28 days and ≥90% reduction in monthly HAE attacks. Results & conclusion: In this NMA, lanadelumab 300 mg administered every 2 weeks or every 4 weeks was associated with statistically significantly higher effectiveness versus berotralstat 150 mg once daily (q.d.) or 110 mg q.d. for both efficacy outcomes assessed.

Retrospective chart review of transplant recipients with cytomegalovirus infection who received maribavir in the Phase 3 SOLSTICE trial: Data at 52 weeks post-maribavir treatment initiation.

BACKGROUND: Cytomegalovirus (CMV) infection is a frequent complication in haematopoietic cell/solid organ transplant (HCT/SOT) recipients. Previous studies report all-cause mortality rates of 31% and 50% in HCT/SOT recipients post-treatment initiation with conventional anti-CMV therapies for refractory or resistant CMV. METHODS: This was a multi-country, retrospective medical chart review study of HCT/SOT recipients with refractory CMV infection with or without resistance (R/R) who were randomized to the maribavir arm in the open-label Phase 3 SOLSTICE trial. Patients came from 21 SOLSTICE sites across 6 countries; each site randomized ≥3 patients to the maribavir arm. Patients were followed for 52 weeks (SOLSTICE trial period: 20 weeks; follow-up chart review period: 32 weeks). The primary outcomes were mortality and graft status. RESULTS: Of 234 patients who were randomized and received maribavir in SOLSTICE, chart abstraction was completed for all 109 patients enrolled across 21 trial sites (SOT, 68/142; HCT, 41/92). At 52 weeks, overall mortality was 15.6% (17/109) and survival probability was 0.84. Among SOT recipients, survival probability was 0.96, and 3 (4.4%) deaths occurred during the chart review period. For the HCT recipients, survival probability was 0.65 with 14 (34.1%) deaths; 8 occurred during SOLSTICE and 6 during the chart review period. No new graft loss or re-transplantation occurred during the chart review period. CONCLUSIONS: Overall mortality at 52 weeks post-maribavir treatment initiation in this sub-cohort of patients from the SOLSTICE trial was lower than that previously reported for similar populations treated with conventional therapies for R/R cytomegalovirus infection.

Duration of frontline therapy and impact on clinical outcomes in newly diagnosed multiple myeloma patients not receiving frontline stem cell transplant.

BACKGROUND: Extended first-line therapy (1LT) has improved clinical outcomes in newly diagnosed multiple myeloma (NDMM). This retrospective study of NDMM patients evaluated the relationship between dose-attenuation of 1LT and duration of therapy (DOT) and DOT on outcomes. METHODS: Adults with NDMM not undergoing stem cell transplant (SCT) from January 1, 2012 toMarch 31, 2018 from the Integrated Oncology Network were included; 300 were randomly selected for chart review. 1LT DOT, time to next treatment (TTNT), progression-free survival (PFS), and overall survival (OS) were estimated using Kaplan-Meier analysis. Marginal structural models evaluated relationships between DOT and TTNT, PFS, and OS at 2 years accounting for confounders and survival bias from the time-dependent nature of DOT. RESULTS: Of 300 chart-reviewed patients, 93 were excluded for incomplete data or meeting exclusion criteria. Among 207 NDMM patients, median age was 74 years; 146 (70.5%) did not receive dose-attenuation during 1LT. Patients with short DOT were older, frailer, with a higher comorbidity burden, and a significantly lower proportion had an Eastern Cooperative Oncology Group PS = 0. As DOT increased, more patients underwent dose-attenuation (p < 0.0001). The median 1LT DOT was 20.9 (95% confidence interval [CI]: 13.9, 26.4) versus 4.2 months (95% CI: 3.2, 4.9) for patients receiving versus not receiving dose-attenuation, respectively (p < 0.0001). After accounting for survival bias, confounder-adjusted TTNT was prolonged with each additional month of 1LT (odds ratio [OR]: 0.76 [95% CI: 0.75, 0.78]); likelihoods of risks of disease progression (OR: 0.87 [95% CI: 0.86, 0.88]) and death at 2 years (OR: 0.72 [95% CI: 0.70, 0.74]) were reduced with each month of 1LT (p < 0.0001 for all outcomes). CONCLUSIONS: Dose-attenuated 1LT was associated with longer DOT among patients with non-SCT NDMM. Each additional month of 1LT was associated with a reduced adjusted likelihood of disease progression and death at 2 years. Dose-attenuation of 1LT can extend DOT; longer DOT may improve clinical outcomes.

Global epidemiology of amyloid light-chain amyloidosis.

BACKGROUND: Amyloid light-chain (AL) amyloidosis is an ultra-rare disease associated with significant morbidity and mortality. Few studies have examined the global epidemiology of this condition. METHODS: This study estimated the diagnosed incidence and 1-year, 5-year, 10-year, and 20-year period prevalence of AL amyloidosis in 2018 for countries in and near Europe, and in the United States (US), Canada, Brazil, Japan, South Korea, Taiwan, and Russia. A systematic literature review (SLR) was conducted to identify country-specific, age- and gender-specific diagnosed incidence of AL amyloidosis and observed survival data-point inputs for an incidence-to-prevalence model. Extrapolations were used to estimate incidence and prevalence for countries without registry or published epidemiological data. RESULTS: Of 171 publications identified in the SLR, 10 records met the criteria for data extraction, and two records were included in the final incidence-to-prevalence model. In 2018, an estimated 74,000 AL amyloidosis cases worldwide were diagnosed during the preceding 20 years. The estimated incidence and 20-year prevalence rates were 10 and 51 cases per million population, respectively. CONCLUSIONS: Orphan medicinal product designation criteria of the European Medicines Agency or Electronic Code of Federal Regulations indicate that a disease must not affect > 5 in 10,000 people across the European Union or affect < 200,000 people in the US. This study provides up-to-date epidemiological patterns of AL amyloidosis, which is vital for understanding the burden of the disease, increasing awareness, and to further research and treatment options.

Lung cancer treatment costs, including patient responsibility, by disease stage and treatment modality, 1992 to 2003.

OBJECTIVES: The objective of this analysis was to estimate costs for lung cancer care and evaluate trends in the share of treatment costs that are the responsibility of Medicare beneficiaries. METHODS: The Surveillance, Epidemiology, and End Results (SEER)-Medicare data from 1991-2003 for 60,231 patients with lung cancer were used to estimate monthly and patient-liability costs for clinical phases of lung cancer (prediagnosis, staging, initial, continuing, and terminal), stratified by treatment, stage, and non-small- versus small-cell lung cancer. Lung cancer-attributable costs were estimated by subtracting each patient's own prediagnosis costs. Costs were estimated as the sum of Medicare reimbursements (payments from Medicare to the service provider), co-insurance reimbursements, and patient-liability costs (deductibles and "co-payments" that are the patient's responsibility). Costs and patient-liability costs were fit with regression models to compare trends by calendar year, adjusting for age at diagnosis. RESULTS: The monthly treatment costs for a 72-year-old patient, diagnosed with lung cancer in 2000, in the first 6 months ranged from $2687 (no active treatment) to $9360 (chemo-radiotherapy); costs varied by stage at diagnosis and histologic type. Patient liability represented up to 21.6% of care costs and increased over the period 1992-2003 for most stage and treatment categories, even when care costs decreased or remained unchanged. The greatest monthly patient liability was incurred by chemo-radiotherapy patients, which ranged from $1617 to $2004 per month across cancer stages. CONCLUSIONS: Costs for lung cancer care are substantial, and Medicare is paying a smaller proportion of the total cost over time.

Good research practices for measuring drug costs in cost-effectiveness analyses: Medicare, Medicaid and other US government payers perspectives: the ISPOR Drug Cost Task Force report--Part IV.

OBJECTIVES: Public programs finance a large share of the US pharmaceutical expenditures. To date, there are not guidelines for estimating the cost of drugs financed by US public programs. The objective of this study was to provide standards for estimating the cost of drugs financed by US public programs for utilization in pharmacoeconomic evaluations. METHODS: This report was prepared by the ISPOR Task Force on Good Research Practices-Use of Drug Costs for Cost-Effectiveness Analysis Medicare, Medicaid, and other US Government Payers Subgroup. The Subgroup was convened to assess the methodological and practical issues confronted by researchers when estimating the cost of drugs financed by US public programs, and to propose standards for more transparent, accurate and consistent costing methods. RESULTS: The Subgroup proposed these recommendations: 1) researchers must consider regulation requirements that affect the drug cost paid by public programs; 2) drug cost must represent the actual acquisition cost, incorporating any rebates or discounts; 3) transparency with respect to cost inputs must be ensured; 4) inclusion of the public program's perspective is recommended; 5) high cost drugs require special attention, particularly when drugs represent a significant proportion of health-care expenditures for a specific disease; and 6) because of variations across public programs, sensitivity analyses for actual acquisition cost, real-world adherence, and generics availability are warranted. Specific recommendations also were proposed for the Medicare and Medicaid programs. CONCLUSIONS: As pharmacoeconomic evaluations for coverage decisions made by US public programs grows, the need for precise and consistent estimation of drug costs is warranted. Application of the proposed recommendations will allow researchers to include accurate and unbiased cost estimates in pharmacoeconomic evaluations.

Randomized Clinical Trial Representativeness and Outcomes in Real-World Patients: Comparison of 6 Hallmark Randomized Clinical Trials of Relapsed/Refractory Multiple Myeloma.

BACKGROUND: Concern has been increasing in oncology regarding randomized clinical trial (RCT) eligibility limiting the generalizability of the findings to real-world populations. Using a large US electronic health record database, we investigated the real-world generalizability of the findings from recent RCTs for relapsed and/or refractory multiple myeloma (RRMM). PATIENTS AND METHODS: Patients with RRMM initiating second-to fourth-line therapy with the control arm of the following RCTs were retrospectively identified and categorized as "RCT eligible" or "RCT ineligible" according to the eligibility criteria: (1) Rd (lenalidomide, dexamethasone)-ASPIRE, TOURMALINE-MM1, POLLUX, and ELOQUENT-2; and (2) Vd (bortezomib, dexamethasone)-CASTOR and ENDEAVOR. Predictors of RCT ineligibility and overall survival were analyzed using logistic regression and Cox regression analysis. RESULTS: Variations in the individual trial ineligibility rates were noted, with up to 72.3% (range, 47.9%-72.3%) of patients not meeting the eligibility criteria for 1 of the 6 hallmark RCTs (n = 788 for Rd; n = 477 for Vd). Other malignancies, cardiovascular disease, acute infection, and renal dysfunction were the common reasons for ineligibility. Advanced age, Charlson comorbidity score of ≥ 2, later therapy lines (3-4), and refractory status to the previous line were independently predictive of RCT ineligibility. RCT-ineligible versus RCT-eligible patients had a significantly greater mortality risk (hazard ratio, Rd, 1.46; Vd, 1.51). CONCLUSION: Most real-world patients with RRMM were ineligible for the hallmark RCTs. The eligibility rates varied across the RCTs, underlining the flawed nature of cross-study comparisons without RCT validation. Overall survival was significantly affected by the inability to meet the criteria, highlighting the limited generalizability of the RCT results. Greater efforts are required to broaden the eligibility criteria to reflect real-world clinical characteristics and narrow the gap between RCT efficacy and the observed effectiveness in real-world patients with RRMM.

Treatment Satisfaction and Burden of Illness in Patients with Newly Diagnosed Multiple Myeloma.

OBJECTIVES: This observational study identified attributes of patient-reported satisfaction with therapy for multiple myeloma (MM), described the treatment-related time burden and indirect costs, and investigated the effect of administration route (oral vs. injectable) on these outcomes among patients with newly diagnosed MM (NDMM) and among caregivers. METHODS: Patients residing in the USA with a self-reported diagnosis of NDMM were recruited from PatientsLikeMe, MyelomaCrowd, and Facebook (16 December 2016 and 6 July 2017) to complete an electronic survey including questions on treatment experience, economic burden, and standardized patient-reported outcome measures, including the Treatment Satisfaction Questionnaire for Medication with three domains (global satisfaction, effectiveness, and convenience) and the Work Productivity and Activity Impairment Questionnaire. Univariate and multivariate analyses identified predictors of patient-perceived treatment satisfaction. RESULTS: Among 188 patients, worse Eastern Cooperative Oncology Group performance status (ECOG PS) was correlated with lower patient-perceived effectiveness and convenience of their current treatment. White race and oral administration route were independently correlated with higher patient-perceived convenience of treatment. Injectable therapy use was associated with a trend towards increased activity impairment (43 vs. 34%; p = 0.05) and significantly higher time burden of treatment administration, with threefold higher adjusted indirect costs of MM therapy compared with solely orally administered therapies (monthly mean $US482 vs. 153; 2016 values; p < 0.0001). CONCLUSIONS: Factors associated with patient-perceived satisfaction with NDMM treatment-ECOG PS, race, administration route-warrant increased attention in shared treatment decision making to help identify patient needs and improve the patient's treatment experience. The use of orally administered therapies could improve patients' activity impairment and reduce the time burden associated with therapy.

Utilization of novel systemic therapies for multiple myeloma: A retrospective study of front-line regimens using the SEER-Medicare data.

The landscape of treatment for multiple myeloma (MM) has significantly changed over the last decade due to novel agents that have shown superiority in efficacy such as proteasome inhibitors (PIs) and immunomodulatory drugs (IMiDs) over traditional therapies. However, the real-world utilization of these new agents has not been studied well. This study evaluated year-to-year changes in treatment choices in a cohort of patients aged 66 or older in the Surveillance, Epidemiology, and End Results (SEER) registry linked with Medicare claims (SEER-Medicare) data who were diagnosed with MM between 2007 and 2011. We identified 2477 symptomatic newly diagnosed patients who were followed for 6 months or more postdiagnosis and treated with systemic therapies but not with stem cell transplantation. Symptomatic patients were identified by evidence of hypercalcemia, renal failure, anemia, or bone lesions (CRAB criteria). The minimum follow-up was imposed to ensure sufficient data to characterize treatment. Our analysis found that the proportion of treated patients increased from 75% in the 2007 cohort to 79% in the 2011 cohort. The share of PI-based regimens including PI plus alkylating agents, PI plus IMiD, and PI-only increased from 9% to 21%, 3% to 11%, and 16% to 22%, respectively, between 2007 and 2011. These findings translate to the share of PI-based regimens having increased from 28% to 55% and that of IMiDs-based regimens (excluding PI plus IMiD) having decreased from 43% to 27%. In conclusion, while the usage of PIs among elderly MM patients increased significantly replacing IMiD-based regimens (with or without alkylating agents but not with PI) between 2007 and 2011, this significant shift did not increase the proportion of treated patients.

Real-world outcomes and factors impacting treatment choice in relapsed and/or refractory multiple myeloma (RRMM): a comparison of VRd, KRd, and IRd.

Lack of head-to-head trials highlights a need for comparative real-world evidence of proteasome inhibitors plus Rd.Methods: In this retrospective, US population-representative EHR study of RRMM patients initiating IRd, KRd, or VRd in line of therapy (LOT) ≥2 between 1/2014 and 9/30/2018, 664 patients were treated in LOT ≥2 with: IRd, n = 168; KRd, n = 208; VRd, n = 357. Median age was 71/65/71 years; 67%/70%/75% had a frailtymodified score of intermediate/frail; 20%/28%/13% had high cytogenetic risk in I-/K-/V-Rd groups. Risk of PI-triplet discontinuation was lower for I- vs. K-Rd (HR: 0.71) and I- vs. V-Rd (HR: 0.85); unadjusted, median TTNTs (months): 12.7/8.6/14.2 (LOT ≥2) and 16.8/9.5/14.6 (LOT 2-3) (I-/K-/V-Rd). Adjusted TTNT was comparable between I-/K-/V-Rd in LOT ≥2 with a TTNT benefit among intermediate/frail patients for I- (HR: 0.70; P=0.04) and V- (HR: 0.73; P<0.05) vs. K-Rd. I/K/V-Rd triplets were comparable in TTNT overall, but IRd and VRd were associated with longer TTNT in intermediate/frail patients than KRd. The results suggest a trial-efficacy/real-world-effectiveness gap, especially for KRd, underlining the limited generalizability of trial results where >50% of patients are excluded. Individualized treatment based on patient characteristics, such as frailty status, is especially pertinent in an elderly RRMM population.

Factors associated with sphincter-preserving surgery for rectal cancer at national comprehensive cancer network centers.

OBJECTIVE: To determine rate and predictors of sphincter-preserving surgery (SPS) for rectal cancer patients treated at specialty institutions. SUMMARY BACKGROUND DATA: SPS has been considered a surrogate for surgical quality, and sphincter preservation is tremendously important to patients. Evidence of association between case volume and SPS rate has prompted recommendations that all rectal cancer patients undergo surgery at specialty institutions. However, rates of SPS, and the factors associated with ability to perform SPS, have not been well-characterized. METHODS: A prospective registry of all colorectal cancer patients treated at 7 National Comprehensive Cancer Network institutions was used to identify patients with clinical stage I-III rectal cancer undergoing surgery (n = 674) between September 2005 and October 2007. Patient, tumor and treatment factors were abstracted; patients' clinical characteristics with and without SPS were compared using descriptive statistics and multivariable logistic regression. RESULTS: Of 674 identified patients (median age, 58.2; 60% male), 520 (77%) had SPS. Of these, 240 had low anterior resection with coloanal anastomosis, 268 low anterior resection without coloanal anastomosis; 12 had other SPS procedures. Sixty-two percent had a temporary diverting stoma. On multivariable analyses, independent predictors of SPS included younger age at diagnosis, proximal location in the rectum, nonfixed tumor, and institution. CONCLUSIONS: SPS rates at National Comprehensive Cancer Network institutions exceed those seen in population-based samples and clinical trials. In addition to expected variation in SPS rates based on patient and tumor characteristics, we identified variation among institutions. Although the optimal rate of SPS remains unknown, this provides areas for further research and potential performance improvement.

Adoption of triplet therapy and clinical outcomes in routine practice among newly diagnosed multiple myeloma patients not receiving frontline stem cell transplant in the USA.

BACKGROUND: Immunomodulator (IMID) and proteasome inhibitor (PI) triplet frontline therapy (FT) in newly diagnosed multiple myeloma (NDMM) trials improve overall survival (OS); reported outcomes in routine practice are lacking. Authors compared outcomes in NDMM patients in the USA by use of triplet vs doublet FTs. METHODS: In this retrospective study of NDMM patients without FT transplant between 1/1/2008 and 6/30/2017, FT was categorized as: PI+IMID-triplet (≥ 3 drugs including PI+IMID), non-PI+IMID-triplet (≥ 3 drugs, not PI+IMID), doublet (≤ 2 drugs). Univariate and multivariate analyses identified FT triplet predictors and compared time-to-next-treatment (TTNT)/OS. RESULTS: Among 4,982 NDMM patients, 68% and 32% initiated doublet and triplet FTs (PI+IMID: 36% in 2017). Triplet FT predictors included: age, cytogenetics, ISS stage, certain CRAB symptoms. Median TTNTPI+IMID-triplet = 18.9 months vs 13.7 (non-PI+IMID-triplet) and 16.5 months (doublet) FTs (P< 0.01); adjusted HRPI+IMID-triplet = 0.86; P= 0.009; HRnon-PI+IMID-triplet = 1.10; P = 0.083 vs doublet FT. Median OSPI+IMID-triplet = 58.7 months vs 43.6 (non-PI+IMID-triplet) and 45.7 months (doublet) FTs (P< 0.01); adjusted HRPI+IMID-triplet = 0.83; P= 0.016; HRnon-PI+IMID-triplet = 1.02; P = 0.727 vs doublet FT. CONCLUSION: PI+IMID-triplet FT is not utilized for most non-frontline-transplant NDMM patients in routine care but is associated with prolonged TTNT/OS.