Indirect treatment comparison of brexucabtagene autoleucel (ZUMA-2) versus standard of care (SCHOLAR-2) in relapsed/refractory mantle cell lymphoma.

The SCHOLAR-2 retrospective study highlighted poor overall survival (OS) with standard of care (SOC) regimens among patients with relapsed/refractory (R/R) mantle cell lymphoma (MCL) who failed a covalent Bruton tyrosine kinase inhibitor (BTKi). In the ZUMA-2 single-arm trial, brexucabtagene autoleucel (brexu-cel; autologous anti-CD19 CAR T-cell therapy) demonstrated high rates of durable responses in patients with R/R MCL who had previous BTKi exposure. Here, we compared OS in ZUMA-2 and SCHOLAR-2 using three different methods which adjusted for imbalances in prognostic factors between populations: inverse probability weighting (IPW), regression adjustment (RA), and doubly robust (DR). Brexu-cel was associated with improved OS compared to SOC across all unadjusted and adjusted comparisons. Hazard ratios (95% confidence intervals) were 0.38 (0.23, 0.61) for IPW, 0.45 (0.28, 0.74) for RA, and 0.37 (0.23, 0.59) for DR. These results suggest a substantial survival benefit with brexu-cel versus SOC in patients with R/R MCL after BTKi exposure.

Progression-Free Survival of Daratumumab Versus Bortezomib Triplet Combination With Lenalidomide and Dexamethasone in Transplant Ineligible Patients With Newly Diagnosed Multiple Myeloma: TAURUS Chart Review Study.

BACKGROUND: Daratumumab, lenalidomide and dexamethasone (DRd) and bortezomib, lenalidomide and dexamethasone (VRd) are preferred regimens for transplant ineligible (TIE) patients with newly diagnosed multiple myeloma (NDMM). Both DRd and VRd demonstrated superior efficacy versus Rd in the MAIA and SWOG S0777 trials, respectively, but there is no head-to-head (H2H) clinical trial comparing their efficacy. Differing populations in the MAIA and S0777 trials make an unadjusted comparison of outcomes challenging and biased. The current TAURUS study is the first real-world H2H study comparing progression-free survival (PFS) among TIE NDMM patients treated with DRd or VRd as first-line (1L) in similar clinical settings. MATERIALS AND METHODS: A multicenter chart review study was conducted at nine sites across the United States. All TIE patients treated with DRd and a randomly selected population of VRd patients were included. TIE NDMM patients aged ≥65 were included if they initiated 1L DRd/VRd between January 2019 and September 2021. PFS was defined as the time from DRd/VRd initiation until disease progression or death. A doubly-robust multivariable Cox regression model combined with inverse probability of treatment weighting (IPTW) methodology was used to compare PFS between cohorts. RESULTS: Weighted cohorts comprised 91 DRd and 87 VRd patients. Thirteen DRd and 24 VRd patients experienced progression/death. Patients treated with DRd had a lower risk of progression/death versus VRd (adjusted hazard ratio: 0.35, 95% confidence interval: [0.17; 0.73]). CONCLUSION: DRd is associated with a significantly lower risk of disease progression or death compared to VRd as 1L treatment for TIE NDMM patients.

Real-world experience among patients with relapsed/refractory mantle cell lymphoma after Bruton tyrosine kinase inhibitor failure in Europe: The SCHOLAR-2 retrospective chart review study.

Mantle cell lymphoma (MCL) after relapse is associated with poor prognosis. No standard of care exists and available evidence for treatments is limited, particularly in patients who fail Bruton tyrosine kinase inhibitor (BTKi) therapy. This multicentre retrospective chart review study, SCHOLAR-2, addresses this knowledge gap and reports on data collected from 240 patients with relapsed/refractory MCL in Europe who were treated with BTKi-based therapy between July 2012 and July 2018, and had experienced disease progression while on BTKi therapy or discontinued BTKi therapy due to intolerance. The median overall survival (OS) from initiation of first BTKi therapy was 14.6 months (95% confidence interval [CI] 11.6-20.0) in the overall cohort, 5.5 months (95% CI 3.9-8.2) in 91 patients without post-BTKi therapy, and 23.8 months (95% CI 18.9-30.1) in 149 patients who received post-BTKi therapy (excluding chimeric antigen receptor T-cell treatment). In the latter group, patients received a median of one (range, one to seven) line of post-BTKi therapy, with lenalidomide-containing regimens and bendamustine plus rituximab being the most frequently administered; the median OS from initiation of first post-BTKi therapy was 9.7 months (95% CI 6.3-12.7). These results provide a benchmark for survival in patients with R/R MCL receiving salvage therapy after BTKi failure.

Time and Cost of Hospitalisation for Salvage Therapy in Adults with Philadelphia Chromosome-Negative B Cell Precursor Relapsed or Refractory Acute Lymphoblastic Leukaemia in Spain.

BACKGROUND: Philadelphia chromosome-negative (Ph-) relapsed or refractory (R/R) B-cell precursor acute lymphoblastic leukaemia (ALL) is rare, and information on its impact on healthcare systems is scarce. OBJECTIVE: To quantify the time and reimbursement associated with hospitalisations of patients with R/R ALL in a Spanish hospital. METHODS: Retrospective review of medical charts identified patients aged ≥ 18 years with Ph- R/R ALL hospitalised between 1998 and 2014. Data were collected from the date of first diagnosis of R/R ALL (index) until death or loss to follow-up. The primary endpoint was the proportion of time hospitalised during chemotherapy. Reimbursement associated with hospitalisations (including associated chemotherapy) was also assessed. RESULTS: Thirty-two patients were eligible for inclusion. Their median age was 41 years, and 50% had a first remission duration of ≤ 1 year; 34% had undergone allogeneic haematological stem-cell transplantation (alloHSCT). Overall, 31 patients had received intensive salvage chemotherapy, during which there were 42 hospitalisations (mean 1.4/patient; mean duration 26 days). Patients spent a mean of 71% of the chemotherapy period in hospital. Total mean reimbursement was €26,417 per patient, almost all (€25,723) attributable to inpatient stays (€18,986/hospitalisation). From the index date to death or loss to follow-up (excluding alloHSCT-related hospitalisations), there were 80 hospitalisations (mean duration 24 days); mean reimbursement was €16,692 per hospitalisation and €41,730 per patient. AlloHSCT (n = 8) involved 18 hospitalisations (mean reimbursement €39,782/hospitalisation; €89,510/patient). CONCLUSION: Data from this sample of patients suggest that hospitalisations in R/R ALL are lengthy and associated with high costs in Spain.

Healthcare burden and reimbursement of hospitalization during chemotherapy for adults with Ph-negative relapsed or refractory B-cell precursor acute lymphoblastic leukemia in France: a retrospective chart review.

OBJECTIVE: Philadelphia chromosome negative [Ph(-)] relapsed or refractory (R/R) B-precursor acute lymphoblastic leukemia (ALL) is an extremely rare condition requiring intensive treatment. This retrospective chart review aimed to quantify hospitalizations and reimbursement in this patient population in France. METHODS: Patients aged ≥18 years and with at least one hospitalization for Ph(-) R/R B-precursor ALL were included in the study. They were relapsed with first remission lasting <12 months, relapsed after first salvage therapy, relapsed any time after hematopoietic stem cell transplant (HSCT), or were refractory to initial or salvage therapy. Data were collected from the index date (first diagnosis of R/R ALL) until death or loss to follow-up. The chemotherapy period was defined as the first chemotherapy date after the index date to the earliest of death, loss to follow-up, last chemotherapy dose plus 30 days, or initiation of HSCT. The primary outcome was the percentage of time hospitalized during the chemotherapy period. RESULTS: Thirty-three patients were included, with a mean age of 49 years. The mean proportion of time spent in the hospital during the chemotherapy period was 46% (95% CI =34-57%). Patients had a mean of 2.2 (SD =1.5) inpatient hospitalizations and the mean length of stay per hospitalization was 16.8 (SD =14.8) days. During the chemotherapy period, the mean amount reimbursed per hospitalization was €31 067 (SD = €4850) and the total hospitalization reimbursement per patient was €68 344. From the index date to death, excluding HSCT, the total reimbursement per patient was €108 873. LIMITATIONS: The sample size was small, although this was expected given the rarity of the patient population. CONCLUSIONS: Adults with Ph(-) R/R B-precursor ALL had repeated and prolonged hospitalizations during salvage chemotherapy. Approximately half the follow-up period was spent in the hospital, and this time was associated with high economic burden in France.

Time savings of weekly versus three-times-per-week administration of erythropoiesis stimulating agents in United States dialysis patients.

OBJECTIVE: Previous research suggests that erythropoiesis stimulating agent (ESA) administration in dialysis is a time-consuming task and switching to less frequently dosed ESAs may offer operational efficiencies. Our objective was to describe and measure the time spent on tasks in the ESA administration process in US dialysis centers, and to estimate potential efficiency gains of using weekly (QW) administration vs three-times-per-week (TIW) administration. METHODS: We conducted a time and motion study of staff time required to prepare, administer and document ESA doses. Dialysis centers using intravenous administration of TIW epoetin alfa (EPO) or QW darbepoetin alfa (DPO) were selected in pairs (one EPO, one DPO) from the same organization to help control for differences in ESA protocols and staffing patterns across organizations. ESA-related tasks were timed by trained observers. Time savings of TIW vs QW administration were estimated. Staff were interviewed about alternate activities that could be accomplished if time were saved in the ESA process. RESULTS: A total of 200 administrations were observed (81 DPO, 119 EPO). A mean of 2.26 (95% CI: 2.1-2.5) minutes per dose were required for ESA administration. ESA process time per administration did not vary significantly between EPO and DPO (p = 0.83). Estimated potential monthly staff time savings for an average facility of 70 patients totaled 23 hours, due to fewer ESA administrations using QW DPO. Patient education and fulfillment of care plans were identified as opportunities for improved care processes that could be implemented if staff time was freed up from the ESA process. LIMITATIONS: Results should not be generalized to other countries, ESAs and/or dosing frequencies. CONCLUSIONS: Switching from TIW EPO to QW DPO can result in time savings due to fewer administrations and provide opportunities to redirect nurse time towards activities aimed at improving patient care.

Staff time and motion assessment for administration of erythropoiesis-stimulating agents: a two-phase pilot study in clinical oncology practices.

BACKGROUND: Erythropoiesis-stimulating agents (ESAs) are used for the management of anaemia in patients with non-myeloid malignancies where anaemia is due to the effect of concomitant myelosuppressive chemotherapy. Assessing the impact of different ESA dosing regimens on office staff time and projected labour costs is an important component of understanding the potential for optimization of oncology practice efficiencies. OBJECTIVES: A two-phase study was conducted to evaluate staff time and labour costs directly associated with ESA administration in real-world oncology practice settings among cancer patients undergoing chemotherapy. The objective of Phase 1 was to determine the mean staff time required for the process of ESA administration in patients with anaemia due to concomitantly administered chemotherapy. The objective of Phase 2 was to quantify and compare the mean staff time and mean labour costs of ESA administered once weekly (qw) with ESA once every 3 weeks (q3w) over an entire course of chemotherapy. METHODS: Phase 1 was a prospective, cross-sectional time and motion study conducted in six private oncology practices in the US based on nine steps associated with ESA administration. Using findings from Phase 1, Phase 2 was conducted as a retrospective chart review to collect data on the number and types of visits in two private oncology practices for patients receiving a complete course of myelosuppressive chemotherapy. RESULTS: In Phase 1, the mean total time that clinic staff spent on ESA administration was 23.2 min for patient visits that included chemotherapy administration (n(chemo) = 37) and 21.5 min when only ESA was administered (n(ESAonly) = 36). In Phase 2, the mean duration of treatment was significantly longer for q3w than qw (53.84 days for qw vs. 113.38 for q3w, p < 0.0001); thus, analyses were adjusted using analysis of covariance (ANCOVA) for episode duration for between-group comparisons. Following adjustment by ANCOVA, qw darbepoetin alfa (DA) patients (n(qw) = 83) required more staff time for ESA + chemotherapy visits and ESA-only visits than q3w patients (n(q3w) = 118) over a course of chemotherapy. Overall, mean total staff time expended per chemotherapy course was greater for patients receiving qw versus q3w DA. Weekly DA dosing was associated with greater projected mean labour costs ($US38.16 vs. $US31.20 [average for 2007-2010]). CONCLUSIONS: The results from this real-world study demonstrate that oncology practices can attain staff time and labour costs savings through the use of q3w ESA. The degree of savings depends on the individual oncology practice's staffing model and ESA administration processes, including those that allow for optimized synchronization of patient visits for ESA and chemotherapy administration. These findings indicate that additional research using standard ESA administration protocols for longer periods of time with a larger number of oncology practices and patients should be conducted to confirm these findings.

The burden of blood transfusion: a utilization and economic analysis--a pilot study in patients with chemotherapy-induced anemia (CIA).

OBJECTIVE: The objective is to measure the burden of blood transfusion of Packed Red Blood Cells (PRBCs) in patients with chemotherapy-induced anemia (CIA) on the institutional outpatient transfusion center. METHODS: This is a retrospective chart review (starting July 1, 2010, working backwards until 120 evaluable patients are accrued) at a single institutional transfusion center in the US. The mean and standard deviation (SD) were calculated for patient's age, pre-transfusion Hgb level, and other transfusion-related activities. RESULTS: One hundred and twenty records were reviewed. The majority included patients who were female (71%), African American (61%), and had either Medicare (48%) or private insurance (39%). The mean patient age was 59 years and the average pre-transfusion Hgb was 7.9 g/dL. The average patient visit to facility ranged from 213 min for one PRBC unit to 411 minutes for three PRBC units. The mean staff time for patient evaluation was 66 minutes. Actual time for transfusion was ∼100 min for each PRBC unit; 90% of patients received two PRBC units. Staff was engaged in direct patient care for an average of 322 min for two PRBC units. The labor cost of transfusion (in 2011 $US) ranged from $46.13-$49.33 per PRBC unit. The estimated fully loaded bundled cost was $596.49 for transfusion of one unit of PRBC. Limitations of the study include: the site included in this study may not be applicable to all sites in practice and the evaluated patient population was varied, with the exception that all patients were treated for some type of malignancy; and the review of blood bank records for 120 patients was not 120 independent events and, as such, may not have adequately captured actual variability. CONCLUSIONS: This analysis quantifies expense in terms of time for administration of the transfusion, as well as costs associated with outpatient blood transfusions.

Erythropoiesis-Stimulating Agent (ESA) Practice Patterns in Patients With Chemotherapy-Induced Anemia (CIA) Treated at Hospital Oncology Clinics.

OBJECTIVES: To characterize erythropoiesis-stimulating agent (ESA) usage initiated in hospital outpatient oncology centers that employ weekly (QW) and every-3-week (Q3W) ESA dosing regimens; describe the frequency of ESA dosing, transfusions, hemoglobin determinations, and anemia-related visits between these 2 regimens; and compare the rates at which inpatient ESA doses are administered on QW versus Q3W schedules. METHODS: This was a retrospective, observational record review evaluating ESA usage in 641 patients from 8 outpatient oncology clinics throughout the United States. Adult patients who initiated myelosuppressive chemotherapy for a documented solid tumor between August 1, 2007 and June 30, 2009 and received their first 3 consecutive outpatient ESA doses on a QW or Q3W schedule were eligible for study inclusion. During a single course of chemotherapy, ESA administrations were recorded as long as ESA therapy was continued on the initial regimen. ESA doses were captured until termination of ESA therapy, until 9 months had elapsed since the first ESA dose, until the patient was switched to another ESA regimen, or until death. ESA administration during inpatient admissions was also recorded. RESULTS: ESA utilization varied between the dosing groups, with fewer ESA doses administered per follow-up month in patients receiving Q3W versus QW ESA therapy (mean, 1 vs 2 doses). Compared to weekly administration, extended-dose ESA therapy also reduced the number of hemoglobin determinations and anemia-related visits without chemotherapy required per follow-up month. Neither the number of transfusions nor the number of packed red blood cell units administered per follow-up month differed between treatment groups. Compared to weekly ESA therapy, Q3W administration reduced costs associated with ESA prescribing and utilization. CONCLUSION: Extended-dose ESA therapy (Q3W dosing) may improve practice efficiency and may be associated with reduced frequencies of hemoglobin determinations and ESA doses required. Q3W dosing may also reduce inpatient ESA utilization by reducing the number of ESA doses required for previously maintained outpatients.

Impact of long-acting growth factors on practice dynamics and patient satisfaction.

OBJECTIVE: To quantify time expended, patient satisfaction, and econometrics associated with short-acting (sargramostim, epoetin alfa) and long-acting (darbepoetin alfa, pegfilgrastim) growth factors. DESIGN: Retrospective resource utilization and prospective two-phase observational study. METHODS: During week 1, time-motion measurements related to patient treatment and drug preparation were collected for scheduling; check-in; phlebotomy; laboratory; and drug preparation, administration, and recording. Drug utilization for one chemotherapy cycle during weeks 2 and 3 was assessed for sargramostim, pegfilgrastim, epoetin alfa, darbepoetin alfa, sargramostim plus epoetin alfa, and pegfilgrastim plus darbepoetin alfa. Patients completed a satisfaction survey. RESULTS: Among 140 patients (mean age 58 yrs), mean chemotherapy cycle duration was 19 days. A total of 268 events were observed. Mean total staff time/patient visit for drug administration was 22.1 minutes, with most time spent on scheduling (5.5 min) and drug preparation, administration, recording (5.2 min). For sargramostim only versus pegfilgrastim only, pegfilgrastim resulted in a 37% reduction (p < 0.01) in all visits and an 85% reduction (p < 0.01) in mean number of doses. For epoetin alfa only versus darbepoetin alfa only, darbepoetin alfa resulted in a 48% reduction (p < 0.01) in mean number of doses. The most common dosage of epoetin alfa was 40,000 U/week (63.6%) and that of darbepoetin alfa was 200 microg every other week (92%), but complete blood counts were obtained weekly. For pegfilgrastim plus darbepoetin alfa versus sargramostim plus epoetin alfa, a 45% reduction (p < 0.01) in total visits and a 77% reduction (p < 0.01) in mean number of doses were noted in the former group. In 69 patients converted to long-acting drugs, 65 actual hours for a single treatment cycle were saved. For patients receiving pegfilgrastim plus darbepoetin alfa, there was a 45% reduction in total clinic visits, 77% reduction in doses, and staff time savings of 1.9 hours/patient/cycle of chemotherapy. Fifty-four patients completed the survey and trended toward neutral in their responses, with moderate disagreement that receiving injections is painful. CONCLUSION: Long-acting growth factors resulted in significant time savings for staff and providers by reducing the number of necessary office visits for drug administration. These time savings can significantly improve the quality of life for patients, as well as nurses, physicians, and caregivers.

Intraoperative use of platelet-plasmapheresis in vascular surgery.

STUDY OBJECTIVE: To determine, in a pilot study, whether pheresis of plasma and platelets before surgical blood loss, with reinfusion of the autologous plasma and platelets after completion of the aortic reconstruction, will result in decreased bleeding and decreased transfusion of allogenic blood components in patients undergoing elective aortic reconstruction. DESIGN: Randomized study. SETTING: University medical center. INTERVENTIONS: Patients were randomized to perioperative (acute) platelet plasmapheresis (APP group) versus conventional blood component therapy (control group). In the APP group, blood was withdrawn after induction of anesthesia, to sequester approximately 300 mL of platelet rich plasma (PRP); platelet poor plasma (PPP) and red blood cells (RBC) were sequestered as well. An autotransfusion device was used to collect and re-infuse autologous RBC during the course of the operation in both groups. After completion of the aortic reconstruction, autologous PRP and PPP were re-infused in the APP group. Blood loss, volume of blood component transfusions, and preoperative and postoperative hemoglobin (Hb), hematocrit (Hct), platelet, international normalized ratio (INR), and activated partial thromboplastin time (aPTT) were recorded. MEASUREMENTS AND MAIN RESULTS: There was no difference between groups in demographics, preoperative laboratory values, or surgical procedures, although more patients were treated for aneurysms (73% vs. 60%) and fewer for occlusive disease (20% vs. 40%) in the control versus APP group. Also, there were no differences between the control and APP groups in duration of operation, blood loss, volume of colloid infused, or volume of allogenic RBC and plasma transfused. Patients in the APP group received a greater volume of crystalloid solution (9.1 +/- 3.4 L vs. 6.8 +/- 3.0 L; p = 0.002), but fewer units of allogenic platelets than the control group (0.7 +/- 1.0 units vs. 0.2 +/- 0.4 units; p < 0.04). There were no differences in postoperative Hb, Hct, INR, aPTT, or fibrinogen. The platelet count was lower in the APP group than in the control group (123 +/- 40 x 10(3)/mm(3) vs. 182 +/- 51 x 10(3)/mm(3); p = 0.004). CONCLUSIONS: Perioperative platelet plasmapheresis led to fewer allogenic platelet transfusions in patients undergoing elective aortic reconstruction. However, there was no decrease in blood loss and no reduction in transfusion of allogenic RBC or plasma. Perioperative platelet plasmapheresis is not recommended for routine use in elective aortic reconstruction.