Treatment patterns, healthcare resource utilization, and costs of patients diagnosed with primary mediastinal B-cell lymphoma in the United States.

AIMS: With the advent of ICD-10-CM codes for PMBCL on 10/01/2015, assessment of treatment patterns and healthcare burden among US patients is possible. This study sought to describe the real-world treatment patterns and economic outcomes of patients with PMBCL. METHODS: Data from the Optum Clinformatics DataMart database was used (January 2013-March 2018). Patients with a first PMBCL ICD-10-CM diagnosis (with or without an antecedent ICD-10-CM diagnosis of DLBCL/other lymphoma, which may have been assigned before PMBCL confirmation) after 10/01/2015 (index date) and no ICD-9-CM diagnosis code for unspecified PMBCL/DLBCL were identified as incident patients. Those with PMBCL ICD-10-CM and unspecified ICD-9-CM diagnosis for PMBCL/DLBCL before 10/01/2015 (index date) were identified as prevalent patients. Patients were observed from the index date up to the earliest among death, end of data availability, or end of continuous health plan enrollment. An adapted algorithm was used to identify lines of therapy (LOT). RESULTS: Among 118 incident and 30 prevalent PMBCL patients, 14% and 20% of patients received ≥2 LOTs, respectively. In incident patients, 48% received ≥1 LOT, 14% ≥2, and 4% ≥3 LOTs. Among prevalent patients, 63% received ≥1 LOT and 20% ≥2 LOTs. The most frequently recorded 1 L therapy was R-CHOP both among incident and prevalent patients. Mean total healthcare costs for incident and prevalent patients were $149,340 and $92,799 per patient per year, respectively, with higher costs ≤12 months ($187,241 and $167,553). Outpatient costs were the main driver (accounting for 60.5% and 64.6% for incident and prevalent patients, respectively). LIMITATIONS: Potential underuse of ICD-10-CM codes shortly after discontinuation of ICD-9-CM codes in 01/2015; regimens identified for each LOT using the claims-based algorithm may not reflect the regimen administered. CONCLUSION: The multiple LOTs necessary for a sizeable minority of patients and the high costs of care highlight the significant unmet needs of PMBCL patients.

Real-World Characteristics, Treatment Patterns, Health Care Resource Use, and Costs of Patients with Diffuse Large B-Cell Lymphoma in the U.S.

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) represents the most common subtype of non-Hodgkin lymphoma in the U.S., but current real-world data are limited. This study was conducted to describe real-world characteristics, treatment patterns, health care resource utilization (HRU), and health care costs of patients with treated DLBCL in the U.S. MATERIALS AND METHODS: A retrospective study was conducted using the Optum Clinformatics Data Mart database (January 2013 to March 2018). Patients with an International Classification of Diseases, Tenth Revision, Clinical Modification diagnosis for DLBCL after October 2015 and no prior International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis for unspecified DLBCL or primary mediastinal large B-cell lymphoma were classified as incident; those with such codes were classified as prevalent. An adapted algorithm identified lines of therapy (e.g., first line [1L]). All-cause HRU and costs were calculated per-patient-per-year (PPPY) among patients with a ≥1L. RESULTS: Among 1,877 incident and 651 prevalent patients with ≥1L, median age was 72 years and 46% were female. Among incident patients, 22.6% had at least two lines (2L), whereas 38.4% of prevalent patients had ≥2L. The most frequent 1L therapy was rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). Incident patients had 1.3 inpatient and 42.0 outpatient (OP) visits PPPY, whereas prevalent patients had 0.8 and 31.3 visits PPPY, respectively. Total costs were $137,156 and $81,669 PPPY for incident and prevalent patients, respectively. OP costs were the main driver of total costs at $88,202 PPPY, which were higher within the first year. CONCLUSION: This study showed that a large portion of patients require additional therapy after 1L treatment to manage DLBCL and highlighted the substantial economic burden of patients with DLBCL, particularly within the first year following diagnosis. IMPLICATIONS FOR PRACTICE: Patients diagnosed with diffuse large B-cell lymphoma (DLBCL) carry a substantial clinical and economic burden. A large portion of these patients require additional therapy beyond first-line treatment. There is significant unmet need among patients with DLBCL who require additional therapy beyond first-line treatment. Patients who do not respond to first-line therapy and are not eligible for transplants have very high health care resource utilization and costs, especially in the first 12 months following initiation of treatment.

Minimal Residual Disease Assessment in Lymphoma: Methods and Applications.

Standard methods for disease response assessment in patients with lymphoma, including positron emission tomography and computed tomography scans, are imperfect. In other hematologic malignancies, particularly leukemias, the ability to detect minimal residual disease (MRD) is increasingly influencing treatment paradigms. However, in many subtypes of lymphoma, the application of MRD assessment techniques, like flow cytometry or polymerase chain reaction-based methods, has been challenging because of the absence of readily detected circulating disease or canonic chromosomal translocations. Newer MRD detection methods that use next-generation sequencing have yielded promising results in a number of lymphoma subtypes, fueling the hope that MRD detection may soon be applicable in clinical practice for most patients with lymphoma. MRD assessment can provide real-time information about tumor burden and response to therapy, noninvasive genomic profiling, and monitoring of clonal dynamics, allowing for many possible applications that could significantly affect the care of patients with lymphoma. Further validation of MRD assessment methods, including the incorporation of MRD assessment into clinical trials in patients with lymphoma, will be critical to determine how best to deploy MRD testing in routine practice and whether MRD assessment can ultimately bring us closer to the goal of personalized lymphoma care. In this review article, we describe the methods available for detecting MRD in patients with lymphoma and their relative advantages and disadvantages. We discuss preliminary results supporting the potential applications for MRD testing in the care of patients with lymphoma and strategies for including MRD assessment in lymphoma clinical trials.

Reevaluation of the pretransplant assessment of mortality score after allogeneic hematopoietic transplantation.

The Pretransplant Assessment of Mortality (PAM) score was developed in 2006 to predict risk of mortality after allogeneic hematopoietic cell transplantation (HCT). Transplant practices have evolved during the past decade, suggesting the need to reevaluate the performance of the PAM score. We used statistical modeling to analyze and recalibrate mortality based on overall PAM scores, its components, and conditioning regimen in a retrospective cohort of 1549 patients who had HCT from 2003 through 2009. PAM scores correlated with mortality, but the effect size was smaller in the current study than in previous studies. PAM scores also demonstrated a stronger association with mortality in patients who received myeloablative conditioning than in those who received reduced-intensity conditioning. In contrast to the original study, carbon monoxide diffusing capacity, serum alanine aminotransferase, and serum creatinine concentrations were no longer significantly associated with 2-year mortality, whereas patient and donor cytomegalovirus serology was associated with mortality in the current cohort. Based on our findings, we developed and tested a revised PAM score for clinicians to estimate survival after allogeneic HCT with myeloablative conditioning regimens for patients with hematologic malignancy. Prognostic models such as the PAM score should be updated and recalibrated periodically to accommodate changes in clinical practice.

Validation and refinement of the Disease Risk Index for allogeneic stem cell transplantation.

Because the outcome of allogeneic hematopoietic cell transplantation (HCT) is predominantly influenced by disease type and status, it is essential to be able to stratify patients undergoing HCT by disease risk. The Disease Risk Index (DRI) was developed for this purpose. In this study, we analyzed 13,131 patients reported to the Center for International Blood and Marrow Transplant Research who underwent HCT between 2008 and 2010. The DRI stratified patients into 4 groups with 2-year overall survival (OS) ranging from 64% to 24% and was the strongest prognostic factor, regardless of age, conditioning intensity, graft source, or donor type. A randomly selected training subgroup of 9849 patients was used to refine the DRI, using a multivariable regression model for OS. This refined DRI had improved prediction ability for the remaining 3282 patients compared with the original DRI or other existing schemes. This validated and refined DRI can be used as a 4- or 3-group index, depending on the size of the cohort under study, for prognostication; to facilitate the interpretation of single-center, multicenter, or registry studies; to adjust center outcome data; and to stratify patients entering clinical trials that enroll patients across disease categories.

Clinical endpoints in allogeneic hematopoietic stem cell transplantation studies: the cost of freedom.

When designing a study for allogeneic hematopoietic stem cell transplantation (HSCT), many choices must be made, including conditioning regimen, stem cell source, and graft-versus-host disease (GVHD) prevention method. For each of these, there are a growing number of options, which can be combined into a bewildering number of possible HSCT protocols. To properly interpret the results of a given strategy and compare them with others, it is essential that there be agreement on the definitions and estimation methods of HSCT endpoints. We report a survey of the recent HSCT literature that confirms the heterogeneity of endpoint definitions and estimation methods used. Unfortunately, this heterogeneity may lead to significant biases in the estimates of key endpoints, including nonrelapse mortality, relapse, GVHD, or engraftment. This can preclude adequate comparisons among studies, even though such comparisons are the major tool with which to improve HSCT outcome. In the context of our survey, we discuss some of the statistical issues that arise when dealing with HSCT endpoints and the ramifications of the choice of endpoint definition, when the endpoint occurs in the context of competing risks. Our hope is to generate discussion and motivate a search for consensus among those who perform transplantations and statisticians.