Utilization of Autologous Hematopoietic Cell Transplantation Over Time in Multiple Myeloma: A Population-Based Study.

PURPOSE: Autologous hematopoietic cell transplantation (autoHCT) is associated with survival benefits in multiple myeloma (MM), but utilization remains low and differs by sociodemographic factors. Prior population-based studies have not fully captured autoHCT utilization or examined relationships between sociodemographic factors and autoHCT trends over time. PATIENTS AND METHODS: We used a novel data linkage between the California Cancer Registry, Center for International Blood and Marrow Transplant Research, and hospitalizations to capture autoHCT in a population-based MM cohort (n = 29, 109; 1991-2016). Due to interactions by treatment era, stratified multivariable Cox proportional hazards regression models determined factors associated with autoHCT. RESULTS: The frequency of MM patients who received autoHCT increased from 5.7% (1991-1995) to 27.4% (2011-2016). In models by treatment era, patients with public/no (vs. private) health insurance were less likely to receive autoHCT (2011-2016 Medicare hazard ratio (HR) 0.70, 95% confidence interval (CI): 0.63-0.78; Medicaid HR 0.81, CI: 0.72-0.91; no insurance HR 0.56, CI: 0.32-0.99). In each treatment era, Black/African American (vs. non-Hispanic White) patients were less likely to receive autoHCT (2011-2016 HR 0.83, CI: 0.72-0.95). Hispanic patients were less likely to undergo autoHCT, most prominently in the earliest treatment era (1991-1995 HR 0.58, 95% CI: 0.37-0.90; 2011-2016 HR 1.07, CI: 0.96-1.19). Patients in lower socioeconomic status neighborhoods were less likely to utilize autoHCT, but differences decreased over time. CONCLUSIONS: Despite increases in autoHCT utilization, sociodemographic disparities remain. Identifying and mitigating barriers to autoHCT is essential to ensuring more equitable access to this highly effective therapy.

Healthcare resource utilization and costs during first salvage therapy for relapsed or refractory acute myeloid leukemia in the United States.

Real-world US healthcare resource utilization (HRU) and costs during first salvage therapy for relapsed/refractory (R/R) acute myeloid leukemia (AML) are described using IBM MarketScan® data (1/1/2007-6/30/2020). Treatments included high- (HIC) and low-intensity chemotherapy (LIC) alone, and gilteritinib, other FLT3 tyrosine kinase inhibitors (TKIs), and venetoclax with or without chemotherapy. Patients were diagnosed with R/R AML at ≥18 years of age between 1/1/2017-12/31/2019. Patient monthly all-cause HRU and costs were analyzed using a fixed-effects model. Data from 399 patients were analyzed (HIC, n = 104; LIC, n = 133; gilteritinib, n = 14; other FLT3 TKIs, n = 68; venetoclax, n = 80). Inpatient HRU was generally highest with HIC, whereas outpatient HRU was generally highest with LIC and venetoclax. Total all-cause incremental monthly costs appeared to be highest with HIC ($171,982) and similar for LIC ($60,512), gilteritinib ($47,218), other FLT3 TKIs ($43,218), and venetoclax ($77,566). Results highlight HRU and cost differences for R/R AML during first salvage therapy.

Linking the Center for International Blood and Marrow Transplant Research Registry to the California Cancer Registry and California Hospital Patient Discharge Data.

Advances in hematopoietic cell transplantation (HCT) have substantially improved patient survival, increasing the importance of studying outcomes and long-term adverse effects in the rapidly growing population of HCT survivors. Large-scale registry data from the Center for International Blood and Marrow Transplant Research (CIBMTR) are a valuable resource for studying mortality and late effects after HCT, providing detailed data reported by HCT centers on transplantation-related factors and key outcomes. This study was conducted to evaluate the robustness of CIBMTR outcome data and assess health-related outcomes and healthcare utilization among HCT recipients. We linked data from the CIBMTR for California residents with data from the population-based California Cancer Registry (CCR) and hospitalization information from the California Patient Discharge Database (PDD). In this retrospective cohort study, probabilistic and deterministic record linkage used key patient identifiers, such as Social Security number, ZIP code, sex, birth date, hematologic malignancy type and diagnosis date, and HCT type and date. Among 22,733 patients registered with the CIBMTR who underwent autologous or allogeneic HCT for hematologic malignancy between 1991 and 2016, 89.0% were matched to the CCR and/or PDD (n = 17,707 [77.9%] for both, n = 1179 [5.2%] for the CCR only, and n = 1342 [5.9%] for the PDD only). Unmatched patients were slightly more likely to have undergone a first autologous HCT than an allogeneic HCT (12.6% versus 9.0%), to have a larger number of missing linkage identifiers, and to have undergone HCT prior to 2010. Among the patients reported to the CIBMTR who matched to the CCR, 85.7% demonstrated concordance of both hematologic malignancy type and diagnosis date across data sources. This linkage presents unparalleled opportunities to advance our understanding of HCT practices and patient outcomes.

Clinical actionability of measurable residual disease (MRD) assessment in the management of patients with hematologic malignancies: a case-based monograph.

New treatments for hematologic malignancies have led to outcomes that are outpacing the ability of traditional measures of response to accurately capture a patient's depth of response and risk of relapse. Assessment of measurable residual disease (MRD) offers a high-sensitivity evaluation for remaining disease present in a patient. MRD is not a surrogate marker for the detection of cancer cells, but rather a direct measure of them. MRD has quickly become an important measurement of response in patients with multiple myeloma and acute lymphocytic leukemia. Retrospective and prospective studies indicate that MRD-negative patients have better outcomes, particularly progression-free and overall survival, compared with patients who are MRD-positive. Two methods have emerged as the primary strategies for assessing MRD: next-generation sequencing (NGS) and next-generation flow (NGF). Both methods measure detectable disease in the bone marrow. The clonoSEQ® Assay, which uses NGS technology, is cleared by the US Food and Drug Administration for the detection and monitoring of MRD in bone marrow samples from patients with multiple myeloma or B-cell acute lymphoblastic leukemia. This monograph discusses the supporting research and clinical use of MRD assessment among patients with multiple myeloma and acute lymphoblastic leukemia.

Cost Effectiveness of Chimeric Antigen Receptor T-Cell Therapy in Multiply Relapsed or Refractory Adult Large B-Cell Lymphoma.

PURPOSE: Two anti-CD19 chimeric antigen receptor T-cell (CAR-T) therapies are approved for diffuse large B-cell lymphoma, axicabtagene ciloleucel (axi-cel) and tisagenlecleucel; each costs $373,000. We evaluated their cost effectiveness. METHODS: We used a decision analytic Markov model informed by recent multicenter, single-arm trials to evaluate axi-cel and tisagenlecleucel in multiply relapsed/refractory, adult, diffuse large B-cell lymphoma from a US health payer perspective over a lifetime horizon. Under a range of plausible long-term effectiveness assumptions, each therapy was compared with salvage chemoimmunotherapy regimens and stem-cell transplantation. Main outcomes were undiscounted life years, discounted lifetime costs, discounted quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (3% annual discount rate). Sensitivity analyses explored uncertainty. RESULTS: In an optimistic scenario, assuming a 40% 5-year progression-free survival (PFS), axi-cel increased life expectancy by 8.2 years at $129,000/QALY gained (95% uncertainty interval, $90,000 to $219,000). At a 30% 5-year PFS, improvements in life expectancy were more modest (6.4 years) and expensive ($159,000/QALY gained [95% uncertainty interval, $105,000 to $284,000]). In an optimistic scenario, assuming a 35% 5-year PFS, tisagenlecleucel increased life expectancy by 4.6 years at $168,000/QALY gained (95% uncertainty interval, $105,000 to $414,000/QALY). At a 25% 5-year PFS, improvements in life expectancy were smaller (3.4 years) and more expensive ($223,000/QALY gained [95% uncertainty interval, $123,000 to $1,170,000/QALY]). Administering CAR-T to all indicated patients would increase US health care costs by approximately $10 billion over 5 years. Price reductions to $250,000 and $200,000, respectively, or payment only for initial complete response (at current prices) would allow axi-cel and tisagenlecleucel to cost less than $150,000/QALY, even at 25% PFS. CONCLUSION: At 2018 prices, it is possible that both CAR-T therapies meet a less than $150,000/QALY threshold. This depends on long-term outcomes compared with chemoimmunotherapy and stem-cell transplantation, which are uncertain. Widespread adoption would substantially increase non-Hodgkin lymphoma health care costs. Price reductions or payment for initial response would improve cost effectiveness, even with modest long-term outcomes.

Assessment of older adult candidates for allogeneic hematopoietic cell transplantation: updates and remaining questions.

INTRODUCTION: Allogeneic hematopoietic cell transplantation (allo-HCT) has seen marked growth among older adults, where chronological age is no longer a barrier to transplant. As allo-HCT expands to older and potentially less fit individuals, prognosticating transplant outcomes in this population remains an ongoing need. Areas covered: This review summarizes pre-transplant assessment tools in optimizing patient selection and predicting transplant outcomes in older adults, including comorbidity indices, psychosocial assessment, geriatric assessment, serum biomarkers, and disease risk. This review also discusses the impact of donor age and clonal hematopoiesis of indeterminate significance on transplant outcomes. Expert commentary: Determining which patients should be referred for transplant remains challenging, especially in older adults. Chronological age is an insufficient prognostic metric, and refining, validating, and developing novel pre-transplant risk assessment tools for geriatric patients offers great potential benefit to the field.

Patient selection for allogeneic hematopoietic cell transplantation (HCT): the evolution of HCT risk assessment.

The use of allogeneic hematopoietic cell transplantation is expanding, with disproportionate growth witnessed in older adults with hematologic malignancies. As the chronological age barrier to transplant fades, refining the pre-hematopoietic cell transplantation (HCT) risk assessment to better capture host health status and disease characteristics is essential. This review summarizes recent efforts to move the field forward towards achieving this goal. Many of these risk assessment tools are currently included in prospective clinical trials; routine clinical use requires greater understanding of how to best incorporate this new information into HCT decision making.

Geriatric assessment to predict survival in older allogeneic hematopoietic cell transplantation recipients.

Allogeneic hematopoietic cell transplantation is increasingly utilized in older adults. This study prospectively evaluated the prognostic utility of geriatric assessment domains prior to allogeneic transplantation in recipients aged 50 years and over. Geriatric assessment was performed prior to transplant, and included validated measures across domains of function and disability, comorbidity, frailty, mental health, nutritional status, and systemic inflammation. A total of 203 patients completed geriatric assessment and underwent transplant. Median age was 58 years (range 50-73). After adjusting for established prognostic factors, limitations in instrumental activities of daily living (HR 2.38, 95%CI: 1.59-3.56; P<0.001), slow walk speed (HR 1.80, 95%CI: 1.14-2.83; P=0.01), high comorbidity by hematopoietic cell transplantation-specific comorbidity index (HR 1.56, 95%CI: 1.07-2.28; P=0.02), low mental health by short-form-36 mental component summary (HR 1.67, 95%CI: 1.13-2.48; P=0.01), and elevated serum C-reactive protein (HR 2.51, 95%CI: 1.54-4.09; P<0.001) were significantly associated with inferior overall survival. These associations were more pronounced in the cohort 60 years and over. Geriatric assessment measures confer independent prognostic utility in older allogeneic transplant recipients. Implementation of geriatric assessment prior to allogeneic transplantation may aid appropriate selection of older adults.

Pilot study of comprehensive geriatric assessment (CGA) in allogeneic transplant: CGA captures a high prevalence of vulnerabilities in older transplant recipients.

Comprehensive geriatric assessment (CGA) is frequently used in oncology to measure the health status of older adults with cancer, but it has not been studied in allogeneic hematopoietic cell transplantation (HCT). We conducted a prospective pilot study of CGA in allogeneic HCT recipients aged ≥50 years to examine the prevalence of vulnerabilities in this population. Patients aged ≥50 years eligible for HCT were enrolled. CGA consisted mainly of self-reported, performance-based, and chart-extracted measures evaluating domains of comorbidity, physical and mental function, frailty, disability, and nutrition. Of 238 eligible patients, 166 completed CGA and underwent HCT. Only 1% had a Zubrod Performance Status score >1; 44% had high comorbidity defined by the Hematopoietic Cell Transplantation Comorbidity Index, and 66% had high comorbidity defined by the Cumulative Illness Rating Scale-Geriatrics. The presence of additional vulnerability was frequent. Disability was present in 40% by Instrumental Activities of Daily Living. Self-reported physical and mental function were significantly lower than population age group norms, 58% were pre-frail, and 25% were frail. Among those with Zubrod Performance Status score of 0, 28% demonstrated disability, 58% were pre-frail, 15% were frail, 35% reported low physical function, and 55% reported low mental function. CGA uncovers a substantial prevalence of undocumented impairments in functional status, frailty, disability, and mental health in older allogeneic HCT recipients.