Role of Patient Characteristics and Insurance Type in Newly Diagnosed Multiple Myeloma Care Disparities.

PURPOSE: Little is known about the role of social determinants of health (SDOH) in the utilization of novel treatments among patients with newly diagnosed multiple myeloma (NDMM). METHODS: This retrospective cohort study used Taussig Cancer Center's Myeloma Patient Registry to identify adults with NDMM between January 1, 2017, and December 31, 2021. Electronic health records data captured treatment with (1) triplet or quadruplet regimen and (2) lenalidomide during the first year after NDMM, and (3) stem-cell transplant (SCT) through December 31, 2022. Multivariable logistic regression models examined associations of demographic/clinical characteristics and SDOH with care patterns. RESULTS: We identified 569 patients with median age at diagnosis of 66 years (IQR, 59-73); 55% were male, 76% White, 23% Black, 1.1% other races, insured by Medicare (51%), private payer (38%), Medicaid (8.3%), and self-pay/other (1.8%). In the multivariable models, self-pay/other payers (adjusted odds ratio [AOR], 0.15 [95% CI, 0.03 to 0.54]) was associated with lower odds of triplet or quadruplet regimen, compared with Medicare. Private insurance (AOR, 0.48 [95% CI, 0.27 to 0.86]) and self-pay/other payers (AOR, 0.16 [95% CI, 0.04 to 0.74]) had lower odds of lenalidomide. Black patients (v White; AOR, 0.47 [95% CI, 0.26 to 0.85]) and patients treated at regional hospitals (v Taussig Cancer Center; AOR, 0.27 [95% CI, 0.12 to 0.57]) had lower odds of SCT. The odds of receiving triplet or quadruplet regimen, lenalidomide, and SCT also varied by the year of NDMM. CONCLUSION: Care for NDMM varied based on race, insurance type, year of diagnosis, and treatment facility. It may be useful to examine the impact of insurance-related characteristics and recent policy initiatives on care disparities.

The story of the development of generic lenalidomide: How one company thwarted the Hatch-Waxman Act to generate billions of dollars in revenue.

Lenalidomide (Revlimid®) was originally approved by the Food and Drug Administration (FDA) in 2005, however, a generic version was not available until 2022. In that time, the price of lenalidomide has increased more than 20 times, and in 2021 alone, it accounted for >$5.8 billion dollars in Medicare Part D spending. This was a direct consequence of legal tactics employed by the manufacturer to thwart development of generic formulations of lenalidomide. In this report, we review the clinical development of lenalidomide, provide background on generic drug manufacturing in the United States (US), describe the steps that the manufacturer took to prevent entry of generic lenalidomide into the US market, and advocate for legislative reform of the FDA approval process and patent law protections in the US.

Real-world assessment of treatment patterns and outcomes in patients with relapsed-refractory multiple myeloma in an Italian haematological tertiary care centre.

Despite significant improvements in therapeutic options, multiple myeloma (MM) patients experience a series of remissions and relapses requiring further lines of therapy (LOTs). We analysed treatment pathways, attrition rates (ARs) and refractoriness patterns across LOTs in 413 MM patients treated from 2011 and 2021. Across LOT-2 to LOT-5 ARs were 26%, 27%, 34% and 37.5%, being 50% for subsequent LOTs. In univariate analysis age over 65 years, international staging system (ISS) II/III, more than two comorbidities, no transplant and no maintenance therapy were significantly associated with AR but regression analysis selected only age over 65 years and more than 2 comorbidities. Median progression-free survival (PFS) was 40.5, 19.5, 10.3, 6 and 4.7 months from LOT-1 to LOT-5. Lenalidomide-refractory patients, among those relapsed after LOT-1, were 26% and 64.5% respectively, in patients starting therapy before 2019 versus in or after 2021. In the two cohorts, 57.5% and 85.5% of patients relapsed after LOT-2 were lenalidomide-refractory. Among patients not relapsed from LOT-1, 80% are receiving continuous lenalidomide and could become lenalidomide-refractory, whereas 91% and 51.5% of patients in LOT-2 could become potential lenalidomide- and daratumumab-refractory respectively. In our analysis the rate of patients reaching subsequent LOTs was higher than previously reported and the increase in early refractoriness would require faster and more efficient treatment licensing processes.

Measurable Residual Disease Assessment Using Next-Generation Flow in Patients With Relapsed and Refractory Multiple Myeloma Treated With a Combination of Carfilzomib, Lenalidomide, and Dexamethasone.

BACKGROUND/AIM: Carfilzomib, lenalidomide, and dexamethasone (KRD) therapy is widely used for patients with relapse/refractory multiple myeloma (RRMM). However, the response in patients who underwent assessment for measurable residual disease (MRD) has not been elucidated in a prospective study. We aimed to clarify the response rate and outcome of KRD therapy in patients in RRMM, including those with MRD. PATIENTS AND METHODS: Twenty-one consecutive RRMM patients treated with KRD at 4 Japanese Centers between September 2016 and October 2018 were enrolled and assessed for MRD in the bone marrow (cut-off: 1×10-5) using the EuroFlow-next-generation flow (NGF) method. RESULTS: The median number of therapy lines before KRD was 3 (range=1-6), and the median number of KRD cycles was 4 (range=1-22). As the best overall response post-KRD therapy, 52% (11/21) of patients achieved a MRD negative complete response, 71% (15/21) achieved stringent complete response/complete response, and 14% (3/21) achieved a very good partial response. MRD negativity was achieved in 12 of 16 (75%) and 14 of 21 (67%) patients during and after KRD treatment, respectively. The 2-year progression-free survival and overall survival from the start of KRD therapy were 100% and 100%, respectively, in MRD-positive cases and 88% and 100%, respectively, in MRD-negative cases (median follow-up=1.8 years). Grade 3/4 toxicities were reported in 15 patients (71%), with thrombocytopenia being the most frequent toxicity (6 patients, 29%). CONCLUSION: This is the first study that prospectively assessed MRD of patients with RRMM after KRD therapy. KRD treatment achieved a high MRD negativity rate and good outcomes with manageable toxicities.

Usability of German hospital administrative claims data for healthcare research: General assessment and use case of multiple myeloma in Munich university hospital in 2015-2017.

OBJECTIVES: To assess the usability of German hospital administrative claims data (GHACD) to determine inpatient management patterns, healthcare resource utilization, and quality-of-care in patients with multiple myeloma (PwMM). METHODS: Based on German tertiary hospital's claims data (2015-2017), PwMM aged >18 years were included if they had an International Classification of Diseases, Tenth Revision, code of C90.0 or received anti-MM therapy. Subgroup analysis was performed on stem cell transplantation (SCT) patients. RESULTS: Of 230 PwMM, 59.1% were men; 56.1% were aged ≥65 years. Hypertension and infections were present in 50% and 67.0%, respectively. Seventy percent of PwMM received combination therapy. Innovative drugs such as bortezomib and lenalidomide were given to 36.1% and 10.9% of the patients, respectively. Mean number of admissions and mean hospitalization length/patient were 3.69 (standard deviation (SD) 2.71 (1-16)) and 12.52 (SD 9.55 (1-68.5)) days, respectively. In-hospital mortality was recorded in 12.2%. Seventy-two percent of SCT patients (n = 88) were aged ≤65 years, 22.7% required second transplantation, and 89.8% received platelet transfusion at a mean of 1.42(SD 0.63 (1-3)). CONCLUSION: GHACD provided relevant information essential for healthcare studies about PwMM from routine care settings. Data fundamental for quality-of-care assessment were also captured.

Clinical and economic burden of tumor lysis syndrome among patients with chronic lymphocytic leukemia/small lymphocytic lymphoma: A real-world US retrospective study.

BACKGROUND: Tumor lysis syndrome (TLS) is a potentially fatal complication of antineoplastic treatments for hematologic malignancies, including chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). Patients developing TLS require intensive care, adding to the overall clinical and economic burden of CLL/SLL. OBJECTIVE: To analyze TLS-associated health care resource utilization (HCRU) and costs in patients with CLL/SLL treated with regimens associated with a high TLS risk (per treatment guidelines), ie, anti-CD20-based chemoimmunotherapy (CIT), lenalidomide, obinutuzumab, or venetoclax. METHODS: Adult patients with CLL/SLL in the MarketScan Databases (January 1, 2006, to April 30, 2020) initiated on CIT, lenalidomide, obinutuzumab, or venetoclax (index date) on or after January 1, 2007, were included in the analysis. Treatment-emergent TLS was defined as TLS occurring in the first 90 days of active treatment. The post-index period was divided into 30-day intervals until the end of the index regimen; intervals pre-TLS were non-TLS intervals and those starting from the TLS event were TLS intervals. Per-patient-per-month (PPPM) HCRU and costs were compared between TLS and non-TLS intervals using generalized linear models adjusted for baseline and time-varying confounders. The proportion of patients in the TLS cohort (patients with treatment-emergent TLS) and non-TLS cohort (patients with no treatment-emergent TLS) who switched treatment within 90 days post-index was compared using Kaplan-Meier rates with logrank P values. RESULTS: Among 6,343 patients with CLL/SLL, 71 (1.1%) developed treatment-emergent TLS (venetoclax: 11.5%; other regimens: 0.8%) after a mean (median) of 12.7 (7.0) days following treatment initiation (mean [median] duration of index regimen: 16.0 [10.0] months); 12 (0.2%) developed clinical TLS (venetoclax: 3.1%; other regimens: 0.1%). TLS was associated with 1.7 times more inpatient admissions (P < 0.001), 2 times more days of inpatient stay (P = 0.012), 22% fewer days of antineoplastic drug administration (P = 0.020), and $3,062 PPPM higher health care costs (P = 0.016), which were mainly driven by $1,688 PPPM higher inpatient costs (P = 0.044). Higher costs were observed among both patients who initiated venetoclax (TLS: $24,170; non-TLS: $20,091) and those who initiated other regimens (TLS: $8,746; non-TLS: $6,915). More patients in the TLS vs non-TLS cohort switched treatment in the first 90 days of treatment (12.6% vs 5.1%, P = 0.006). CONCLUSIONS: TLS was associated with a substantial cost burden (driven by inpatient costs) and higher rate of treatment switching (vs non-TLS cohort) in patients with CLL/SLL treated with CIT, obinutuzumab, lenalidomide, or venetoclax. The risk of treatment-emergent TLS and associated incremental HCRU and costs, as well as the potential impact on quality of life, should be weighed when evaluating the risk-benefit of therapies in CLL/SLL management. DISCLOSURES: Dr Rogers has received research funding from Genentech, AbbVie, Novartis, and Janssen (not for the present study); consulting fees from Acerta Pharma, AstraZeneca, Innate Pharma, Pharmacyclics, Genentech, and AbbVie; and travel funding from AstraZeneca. Mr Emond, Mr Kinkead, Ms Lafeuille, and Mr Lefebvre are employees of Analysis Group, Inc., which has provided paid consulting services to Janssen Scientific Affairs, LLC. Drs Lu and Huang are employees of Janssen Scientific Affairs, LLC, and stockholders of Johnson & Johnson. Ms Côté-Sergent was an employee of Analysis Group, Inc., at the time the study was conducted. This study was funded by Janssen Scientific Affairs, LLC. The sponsor was involved in the study design; data collection, analysis, and interpretation; manuscript writing; and the decision to publish the article.

Association of High-Deductible Health Plan Enrollment With Spending on and Use of Lenalidomide Therapy Among Commercially Insured Patients With Multiple Myeloma.

Importance: High-deductible health plans (HDHPs) require high upfront cost-sharing, which has been associated with suboptimal anticancer medication uptake and adherence. Whether HDHP enrollment has limited the affordability and use of lenalidomide therapy among commercially insured patients with multiple myeloma is unknown. Objective: To assess the association of HDHP enrollment with out-of-pocket spending on and adherence to lenalidomide therapy. Design, Setting, and Participants: In this cohort study, data were obtained from the IBM MarketScan Commercial Claims and Encounters Database for adults aged 18 to 64 years with multiple myeloma who newly initiated lenalidomide therapy between April 1, 2013, and June 30, 2017. Quantile regression and modified Poisson regression evaluated out-of-pocket spending, and group-based trajectory models and multinomial logistic regression examined patterns of and factors associated with adherence. Analyses were conducted from April to August 2020. Exposures: High-deductible health plan enrollment in the 3 months before and 6 months after initiation of lenalidomide therapy. Main Outcomes and Measures: Distribution of out-of-pocket spending, the probability of paying more than $100 for the first and any lenalidomide prescription fill, and monthly lenalidomide therapy adherence using the proportion of days covered (≥80%). Results: Of the 3163 commercially insured patients who initiated lenalidomide therapy (median age, 57 years [IQR, 53-60 years for HDHP enrollees and 52-61 years for non-HDHP enrollees]), 328 (10.4%) were enrolled in HDHPs and 1769 (55.9%) were women. Among the highest spenders (95th percentile), HDHP enrollees paid $376 (95% CI, -$28 to $780) and $217 (95% CI, $106-$323) more for their first and any lenalidomide prescription fill, respectively, compared with non-HDHP enrollees in the 6 months after initiation. High-deductible health plan enrollment was also associated with an increased risk of paying more than $100 for the initial (adjusted risk ratio [aRR], 1.30 [95% CI, 1.13-1.50]) and any (aRR, 1.26 [95% CI, 1.12-1.42]) lenalidomide prescription fill. Three adherence trajectory groups were identified: those with high adherence (n = 1273), late nonadherence (n = 1084), and early nonadherence (n = 805). High-deductible health plan enrollment was not associated with adherence group assignment. Conclusions and Relevance: In this cohort study, HDHP enrollment was associated with higher out-of-pocket spending per lenalidomide prescription fill; however, no statistically significant differences in adherence patterns between HDHP and non-HDHP enrollees were observed. Patient (eg, perceptions of treatment benefits), payer (eg, out-of-pocket maximums), and clinician (eg, counseling patients on disease severity) factors may have limited the potential for nonadherence among commercially insured patients who initiated lenalidomide therapy.

Lenalidomida para terapia de manutenção em pacientes com mieloma múltiplo submetidos ao transplante de células-tronco hematopoiéticas / Lenalidomide for maintenance therapy in patients with multiple myeloma submerged in or hematopoietic stem cell transplant

INTRODUÇÃO: O mieloma múltiplo é uma neoplasia de plasmócitos com incidência anual no Brasil de 1,24 casos a cada 100.000 habitantes. Apesar de avanços no tratamento da doença, o mieloma múltiplo é considerado incurável e o objetivo da terapia é induzir a remissão e prolongar a sobrevida do paciente, preservando sua qualidade de vida. Uma parte dos pacientes é considerada elegível para realização de TCTH após a administração de medicamentos com atividade antimieloma. Após o TCTH, os pacientes podem receber a terapia de manutenção, que consiste na administração prolongada de medicamentos com baixa toxicidade na tentativa de prevenir a progressão da doença. A lenalidomida é um imunomodulador que pode ser utilizado na terapia de manutenção. Desta forma, o objetivo deste Relatório é comparar eficácia, segurança, custo-efetividade e impacto orçamentário da lenalidomida em relação à talidomida, imunomodulador disponível no SUS. TECNOLOGIA: Lenalidomida. PERGUNTA: A lenalidom

Lenalidomida para pacientes com mieloma múltiplo inelegíveis ao transplante de células-tronco hematopoiéticas / Lenalidomide for patients with multiple myeloma ineligible for stem cell transplant hematopoietic

INTRODUÇÃO: O mieloma múltiplo é uma neoplasia de plasmócitos com incidência anual no Brasil de 1,24 casos a cada 100.000 habitantes. Apesar de avanços no tratamento da doença, o mieloma múltiplo é considerado incurável e o objetivo da terapia é induzir a remissão e prolongar a sobrevida do paciente preservando sua qualidade de vida. Um dos principais tratamentos é o TCTH. No entanto, uma parcela significativa dos pacientes não é elegível ao TCTH podendo ser apenas submetida a medicamentos. A lenalidomida é um imunomodulador que pode ser utilizado na terapia de indução e manutenção nesses pacientes. Desta forma, o objetivo deste Relatório é comparar eficácia, segurança, custo-efetividade e impacto orçamentário da lenalidomida em relação à talidomida, imunomodulador disponível no SUS, em pacientes com mieloma múltiplo inelegíveis ao TCTH. TECNOLOGIA: Lenalidomida. PERGUNTA: A lenalidomida é mais eficaz, segura e custo-efetiva em esquemas com dois ou três medicamentos comparada à talidomida em esquemas terapêuticos com dois ou três medicamentos para o t

Cost-effectiveness of daratumumab in combination with lenalidomide and dexamethasone for relapsed and/or refractory multiple myeloma.

OBJECTIVE: This study evaluates the cost-effectiveness of daratumumab (D) in combination with lenalidomide and dexamethasone (Rd) for treatment of relapsed and/or refractory multiple myeloma in patients who have received at least one prior therapy in Singapore. METHODS: A 3-state partitioned survival model was developed to evaluate the cost-effectiveness of lenalidomide and dexamethasone with or without daratumumab from a healthcare system perspective over 10 years. Clinical inputs were obtained from the POLLUX trial. Health state utilities were derived from the literature and direct medical costs obtained from public healthcare institutions. Sensitivity and scenario analyses were conducted to explore uncertainties. RESULTS: DRd was associated with a high base-case incremental cost-effectiveness ratio (ICER) of US$576,247 per quality-adjusted life year (QALY) gained, compared with Rd. According to one-way sensitivity analysis, ICER was most heavily influenced by time horizon, discount rate for outcomes, progression-free utility and cost of daratumumab. Regardless of the variation, DRd remained not cost-effective. Even when the cost of both daratumumab and lenalidomide dropped by 20% and 80%, the ICERs remained high at US$470,400 and US$152,860 per QALY gained. CONCLUSIONS: At current prices, the addition of daratumumab to lenalidomide and dexamethasone does not represent cost-effective use of healthcare resources in Singapore.

Phase Ib trial of lenalidomide as post-remission therapy for older adults with acute myeloid leukemia: Safety and longitudinal assessment of geriatric functional domains.

BACKGROUND AND OBJECTIVES: Novel, non-cytotoxic agents are driving a paradigm shift for treatment of older adults with acute myeloid leukemia (AML). Older patients who initially receive intensive cytotoxic induction may choose to not proceed with cytotoxic consolidation therapy. Lenalidomide is an orally-administered immunomodulatory small molecule with activity in AML and a favorable safety profile in older adults with active leukemia. We conducted a phase Ib study of lenalidomide as post-remission therapy in older adults and assessed its impact on geriatric functional domains. MATERIALS AND METHODS: Participants were patients with AML over age 60 years who had undergone induction therapy and were poor candidates for cytotoxic consolidation. Lenalidomide was administered for 28 days in three dose cohorts. A Bayesian dose-escalation method determined cohort assignment and maximum tolerated dose (MTD). Geriatric assessment (GA) was performed before and after the cycle of lenalidomide. RESULTS: Nineteen patients with median age 68 were treated with at least one 28-day course of lenalidomide. Dose-limiting toxicities were observed in three participants at 25 mg, zero participants at 35 mg, and one participant at 50 mg. MTD was 35 mg. Median relapse-free survival was 4.3 months. GA was completed before and after treatment in fifteen patients, demonstrating improved cognitive function and no changes in physical, psychological, or social function after lenalidomide. CONCLUSION: Lenalidomide can be safely administered to older adults with AML with preservation of functional domains important to older patients. Serial GA can be performed in a novel drug study as a tool to characterize treatment tolerability.

Economic evaluation of polatuzumab-bendamustine-rituximab vs. tafasitamab-lenalidomide in transplant-ineligible R/R DLBCL.

AIM: Polatuzumab vedotin-bendamustin-rituximab (PBR) and tafasitamab-lenalidomide (Tafa-L) were approved recently for relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) in autologous stem cell transplant (ASCT) ineligible patients. We performed an industry-independent pharmacoeconomic evaluation of both regimens over a 5-year (y) time horizon (US payer perspective; 2020 USD). METHODS: Survival curves, treatment costs, and utility values were applied in a three-state Markov model (progression-free survival (PFS), post-progression survival (PPS), death) to estimate the incremental follow-up (ICER) and cost-utility ratios (ICUR). A novel metric of the incremental cost per 1% gain in the probability of achieving objective response (OR), PFS, and OS were estimated. RESULTS: Five-year Tafa-L costs ($470,119) exceeded PBR's ($249,217) by $220,902 with incremental gains of 0.71 life-years (LY) and 0.32 quality-adjusted life-years (QALY); yielding ICER of $310,041/LYg and ICUR of $694,241/QALYg. Tafa-L had favorable PFS and OS rates over PBR with adjusted differences of +19.2 and +34.1%, respectively at trial follow-up (∼2 years), with corresponding 5 years differences in survival of +7.8% in PFS and +21.4% in OS. The incremental cost per 1% gain in the probability of achieving OR, PFS and OS at follow-up were $8,479, $6,359, and $3,583; and $28,321 and $10,323 for PFS and OS at 5 years. CONCLUSION: The sustained Tafa-L treatment demonstrated better survival outcomes than 6-cycle PBR though at a greater cost. The incremental costs to gain a 1% improvement in 2 and 5 years survival outcomes with Tafa-L over PBR were modest, underscoring the longer-term benefit of Tafa-L over PBR in patients ineligible for or opting out of ASCT.

PLAIN LANGUAGE SUMMARYTwo new medication regimens were approved recently for relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL): six cycles of polatuzumab vedotin-bendamustine-rituximab (PBR) and continuous twice-monthly treatment with tafasitamab-lenalidomide (Tafa-L). Both treatments are expensive, but Tafa-L more so because it requires continuous treatment versus the maximum 6 cycles of PBR. However, Tafa-L may have better progression-free (PFS) and overall survival (OS) outcomes. Is this worth the additional money?We conducted a cost-effectiveness analysis comparing Tafa-L to PBR. After calculating the differenced in costs and the progression-free and overall survival, we determined the additional cost to gain a life year (LY) or quality-adjusted life year (QALY) over 5 years. We also introduced a novel metric: how much it would cost extra to gain, with Tafa-L treatment, an improvement in progression-free or overall survival of 1% over the survival afforded by PBR. Treatment with Tafa-L over PBR would cost an extra $220,902 for a gain of 0.71 life years (standardized, $310,041/LYgained) and 0.32 quality-adjusted life years ($694,241/QALYgained). Importantly, two years of Tafa-L treatment increased the likelihood of progression-free survival by +19.2% and overall survival by 34.1% over PBR; extending to +7.8% in progression-free survival and +21.4% in overall survival at five years. It cost an additional $28,321 per 1% gain in likelihood in progression-free survival and $10,323 per 1% gain in overall survival after 5 years. Summarized, the increased costs of Tafa-L translate into significantly better progression-free and overall survival.

Cost-effectiveness of adding daratumumab or bortezomib to lenalidomide plus dexamethasone for newly diagnosed multiple myeloma.

BACKGROUND: Multiple myeloma survival rates are steadily increasing due to availability of new drug classes used in combination with corticosteroids and chemotherapy. The latest treatments are daratumumab or bortezomib in combination therapy with lenalidomide and dexamethasone (Rd). Daratumumab, a CD38-targeted, human IgG1k monoclonal antibody, and bortezomib, a proteasome inhibitor, are both approved as regimens for transplant-ineligible relapsed/refractory multiple myeloma (RRMM). There have been cost-effectiveness analyses for daratumumab and bortezomib use in RRMM, but there are limited data regarding cost-effectiveness for daratumumab or bortezomib use in newly diagnosed multiple myeloma patients who are ineligible for stem cell transplantation. OBJECTIVE: To compare the cost-effectiveness of 3 separate regimens-(1) daratumumab, lenalidomide, and dexamethasone triple therapy (DRd); (2) bortezomib and lenalidomide plus dexamethasone triple therapy (VRd); and (3) lenalidomide plus dexamethasone (Rd)-in patients with multiple myeloma ineligible for autologous stem cell transplant. METHODS: A 2-state Markov model was developed using a US health system perspective and lifetime time horizon. Transition probabilities were calculated from the latest progression-free survival data reported in two phase 3 randomized controlled trials-MAIA and SWOG S0777-and extrapolated using a Weibull distribution based on the Hoyle Henley method. National data sources were used to obtain costs in 2019 US dollars, discounted by 3%. Health state utilities from available literature were applied to each health state. Utility decrements for adverse events were individualized in each choice branch with utility decrement weighted by the percentage of patients who experienced the adverse event in the MAIA and SWOG S0777 trials. We assumed a treatment would be cost-effective at a willingness to pay (WTP) of $150,000 per progression-free quality-adjusted life-year ($/PFQALY). One-way and probabilistic sensitivity analyses were conducted. RESULTS: Rd standard therapy had the lowest overall cost at $329,867, followed by VRd at $385,434 and DRd with the highest overall total cost at $626,900. Rd was estimated to result in the least amount (1.24) of PFQALYs, followed by VRd at 1.35 PFQALYs and DRd at 1.52 PFQALYs. With a WTP threshold of $150,000 per PFQALY, VRd was not cost-effective compared with Rd standard therapy, with an incremental cost-effectiveness ratio (ICER) of $530,256 per PFQALY. DRd was not cost-effective compared with VRd (ICER = $1,396,318 per PFQALY), nor as compared with Rd standard therapy (ICER = $1060,832). One-way sensitivity analysis showed that our model was sensitive to cost of DRd, VRd, and Rd drugs. Probabilistic sensitivity analysis showed that only at a WTP threshold of $550,000 was VRd cost-effective for 40% of iterations. There were no reasonable WTP thresholds, up to $800,00, where DRd became more cost-effective than VRd. CONCLUSIONS: This study is the first analysis to directly compare the cost-effectiveness of 3 acceptable chemotherapy treatment regimens for patients with multiple myeloma ineligible for autologous stem cell transplant. Neither DRd nor VRd triple therapy were found to be cost-effective vs Rd. Further cost-effectiveness analyses that include overall survival data for daratumumab and bortezomib triple therapies are needed to demonstrate an ICER in QALYs. DISCLOSURES: No funding was received for this study. At the time of this study, Narsipur was a UCSF-Actelion Clinical Research and Medical Communications Fellow, unrelated to this study. The other authors have nothing to disclose.

Cost-effectiveness of lenalidomide plus rituximab versus rituximab monotherapy in patients with previously treated follicular lymphoma: a societal view.

INTRODUCTION: Efficacy of lenalidomide plus rituximab (R-LEN) compared to rituximab monotherapy (R-mono) for patients with previously treated follicular lymphoma (FL) was investigated in AUGMENT (NCT01938001). Our aim was to evaluate the cost-effectiveness of R-LEN versus R-mono in this setting from a Dutch perspective. AREAS COVERED: Cost-effectiveness was assessed through a partitioned survival model from three perspectives (i.e. societal, healthcare, and societal, including future non-medical costs). Patient-level data from AUGMENT informed effectiveness parameters (i.e. long-term survival) and health state utilities. Resource use and prices were based on AUGMENT and the literature. Clinical experts validated efficacy input parameters and results. Uncertainty was explored through sensitivity and scenario analyses. EXPERT OPINION: R-LEN resulted in 1.7 incremental discounted quality-adjusted life years (QALYs). Total incremental discounted costs were 67,161 EUR from a societal perspective. In conclusion, R-LEN was cost-effective at a willingness-to-pay (WTP) threshold of 50,000 EUR/QALY in the base-case analyses(incremental cost-effectiveness ratio = 40,493 EUR/QALY). Scenario and sensitivity analyses indicated some level of uncertainty regarding this conclusion, depending on the chosen WTP-threshold and perspective.

Minimal residual disease assessment by multiparameter flow cytometry in transplant-eligible myeloma in the EMN02/HOVON 95 MM trial.

Minimal residual disease (MRD) by multiparameter flow cytometry (MFC) is the most effective tool to define a deep response in multiple myeloma (MM). We conducted an MRD correlative study of the EMN02/HO95 MM phase III trial in newly diagnosed MM patients achieving a suspected complete response before maintenance and every 6 months during maintenance. Patients received high-dose melphalan (HDM) versus bortezomib-melphalan-prednisone (VMP) intensification, followed by bortezomib-lenalidomide-dexamethasone (VRd) versus no consolidation, and lenalidomide maintenance. Bone marrow (BM) samples were processed in three European laboratories, applying EuroFlow-based MFC protocols (eight colors, two tubes) with 10-4-10-5 sensitivity. At enrollment in the MRD correlative study, 76% (244/321) of patients were MRD-negative. In the intention-to-treat analysis, after a median follow-up of 75 months, 5-year progression-free survival was 66% in MRD-negative versus 31% in MRD-positive patients (HR 0.39; p < 0.001), 5-year overall survival was 86% versus 69%, respectively (HR 0.41; p < 0.001). MRD negativity was associated with reduced risk of progression or death in all subgroups, including ISS-III (HR 0.37) and high-risk fluorescence in situ hybridization (FISH) patients (HR 0.38;). In the 1-year maintenance MRD population, 42% of MRD-positive patients at pre-maintenance became MRD-negative after lenalidomide exposure. In conclusion, MRD by MFC is a strong prognostic factor. Lenalidomide maintenance further improved MRD-negativity rate.

Survival, health care resource utilization and expenditures of first-line treatments for multiple myeloma patients ineligible for transplant in Taiwan.

BACKGROUND: We aimed to provide real-world information on survival, health care resource utilization (HCRU), and expenditures related to various first lines of therapy (1LOTs) in newly diagnosed multiple myeloma (NDMM) patients who were transplant ineligible (TI). PATIENTS AND METHODS: From the Taiwan National Health Insurance Database (2008-2016), we identified 1,511 NDMM-TI patients who had received 1LOT since June 2012. We categorized 1LOT regimens into four groups: bortezomib (V)+thalidomide (T), V, T, and non-V/T. Patients' characteristics were collected. The overall survival (OS), event-free survival (EFS), frequencies of HCRU (hospitalization, visiting outpatient and emergency departments), and related expenditures within one year after commencement of the 1LOT were evaluated and compared. RESULTS: The mean age of the included patients was 71.3 (SD 10.7) years, and 40.4% of patients had a CCI score ≥3. Most patients (747; 49.4%) were in the V+T group and, after adjusting for covariates, had a significantly longer OS (median, 22.2 months) and EFS (9.1 months) than those in the T group (12.6 and 4.5 months, respectively) and the non-V/T group (12.2 and 3.2 months, respectively), but they were mostly comparable with patients in the V group (23.8 and 6.6 months, respectively). Compared to those in the V+T group, patients in the T and non-V/T groups had 29% and 39% fewer outpatient visits and 15% and 24% lower total expenditure, respectively. CONCLUSION: Our real-world data consolidate evidence for the effectiveness of bortezomib-containing regimens as the 1LOT in NDMM-TI patients at the expense of more outpatient visits and higher total costs.

Clinical effectiveness of DNA methyltransferase inhibitors and lenalidomide in older patients with refractory anemia with ring sideroblasts: a population-based study in the United States.

Existing studies regarding the role of DNA methyltransferase inhibitors (DNMTi) and lenalidomide in refractory anemia with ring sideroblasts (RARS) are limited. Using the surveillance, epidemiology, and end results-medicare database, we assembled a population-based cohort of older adults diagnosed with non-del(5q) lower-risk myelodysplastic syndromes during 2007-2015. Of 2167 patients, 30% had RARS. About 16% of RARS and non- ring sideroblasts (RS) patients received DNMTi. RARS patients were more likely to receive lenalidomide (11.1% vs. 7.1%, p < 0.01). Among patients who were transfusion-dependent at treatment initiation, 55.6% of those treated with DNMTi only and 42.5% treated with lenalidomide only achieved red blood cell transfusion independence (RBC-TI) for a median duration of 21 and 12 weeks, respectively. RS status did not impact rate of RBC-TI. RARS patients had a significantly better survival, and the median survival of RARS patients varied by treatment group. In this population-based study of older RARS patients, DNMTi and lenalidomide were clinically active.

Expert review on soft-tissue plasmacytomas in multiple myeloma: definition, disease assessment and treatment considerations.

In this review, two types of soft-tissue involvement in multiple myeloma are defined: (i) extramedullary (EMD) with haematogenous spread involving only soft tissues and (ii) paraskeletal (PS) with tumour masses arising from skeletal lesions. The incidence of EMD and PS plasmacytomas at diagnosis ranges from 1·7% to 4·5% and 7% to 34·4% respectively. EMD disease is often associated with high-risk cytogenetics, resistance to therapy and worse prognosis than in PS involvement. In patients with PS involvement a proteasome inhibitor-based regimen may be the best option followed by autologous stem cell transplantation (ASCT) in transplant eligible patients. In patients with EMD disease who are not eligible for ASCT, a proteasome inhibitor-based regimen such as lenalidomide-bortezomib-dexamethasone (RVD) may be the best option, while for those eligible for high-dose therapy a myeloma/lymphoma-like regimen such as bortezomib, thalidomide and dexamethasone (VTD)-RVD/cisplatin, doxorubicin, cyclophosphamide and etoposide (PACE) followed by SCT should be considered. In both EMD and PS disease at relapse many strategies have been tried, but this remains a high-unmet need population.

Burden of Treatment-Induced Peripheral Neuropathy in Patients with Multiple Myeloma in Sweden.

INTRODUCTION: Treatment-induced peripheral neuropathy (TIPN) is a complication of multiple myeloma (MM) treatment. OBJECTIVE: This real-world, retrospective study used electronic medical record (EMR) data from 3 Swedish clinics to assess the occurrence and economic burden of TIPN in patients with MM. METHODS: Eligible patients had an MM diagnosis in the Swedish Cancer Registry between 2006 and 2015 and initiated treatment during that period. Follow-up was until last EMR visit, death, or study end (April 2017). The current analyses included patients receiving bortezomib, lenalidomide, carfilzomib, or thalidomide at any treatment line. To discern healthcare resource utilization (HCRU) and costs associated with TIPN from other causes, patients with TIPN were matched with those without on baseline characteristics, treatment, and line of therapy. All analyses were descriptive. RESULTS: Overall, 457 patients were included; 102 (22%) experienced TIPN. Patients experiencing TIPN during first-line treatment mostly received bortezomib-based regimens (n = 48/57 [84%]); those with TIPN during second- and third/fourth-line treatment mostly received lenalidomide/thalidomide-based regimens (19/31 [61%], 8/14 [57%], respectively). Patients with TIPN had higher HCRU/costs than those without TIPN (mean differences in hospital outpatient visits: 5.2, p = 0.0031; total costs per patient-year: EUR 17,183, p = 0.0007). CONCLUSIONS: Effective MM treatments associated with a reduced incidence of TIPN could result in decreased healthcare expenditure.