Infusion Schedule Research Articles

Assessing the repercussions of COVID-19 pandemic on symptoms, disease management, and emotional well-being in patients with inflammatory bowel disease: a multi-site survey study

Background Coronavirus disease 2019 (COVID-19) pandemic has created numerous challenges in provision of safe and effective care for patients with Inflammatory Bowel Disease (IBD). In this study, we surveyed patients with IBD to highlight the impact of the pandemic on their IBD symptoms, management, and well-being. Methods A multi-site survey was administered to patients with IBD. We evaluated patient’s symptoms, medications changes, seeking medical attention, eating behaviors, sleep patterns, stress, self-reported anxiety and depression. The survey also measured emotional impact of the pandemic using the validated Pandemic Emotional Impact Scale (PEIS) and resilience using the Brief Resilience Scale (BRS). Logistic, ordinal, and linear regression models were utilized to perform sensitivity analyses. Results The response rate to the survey was 61%. Of 391 surveyed patients, 21.1% reported worsened gastrointestinal symptoms, 17.5% reported changing biologic medication infusion schedule, 18.7% reported changing medication regimen, 43.6% attended at least one telemedicine visit with their gastroenterologist, 16.5% reported a less healthy diet, 40.5% reported worsening sleep, 63.7% reported more stress, and 65.3% reported feeling more vulnerable than before the pandemic. Women and participants with self-reported anxiety and depression were more likely to have worse symptoms, psychological well-being and daily functioning. Increased PEIS scores and decreased BRS scores were associated with worse outcomes. Conclusions COVID-19 pandemic has impacted symptoms, disease management and well-being for patient with IBD, more prominently in patients who suffer from anxiety and depression. Utilizing PEIS and BRS scores as screening tools could help better tailor outreach and follow-up to support these patients.

A Prospective Phase I/II Trial to Jointly Optimize the Administration Schedule and Dose of Melphalan for Injection (Evomela) As a Preparative Regimen for Autologous Hematopoietic Stem Cell Transplantation in Newly Diagnosed Multiple Myeloma

A Prospective Phase I/II Trial to Jointly Optimize the Administration Schedule and Dose of Melphalan for Injection (Evomela) As a Preparative Regimen for Autologous Hematopoietic Stem Cell Transplantation in Newly Diagnosed Multiple Myeloma

Do MYC Alterations Matter in HIV-Associated Large B Cell Lymphomas? the “Euromyc” Study (a European retrospective study)

Do MYC Alterations Matter in HIV-Associated Large B Cell Lymphomas? the “Euromyc” Study (a European retrospective study)

Consequences of adding standardized levosimendan infusion in VA-ECMO weaning protocol

Abstract Introduction Employment of VA-ECMO in the treatment of refractory cardiogenic shock is increasing. Weaning rates are highly variable between studies. Methods We designed a retrospective observational single-centre study in order to analyse procedural success rate after including scheduled and standardized levosimendan infusion as part of our weaning protocol. Procedural success rate includes weaning from VA-ECMO, bridging to other mechanical circulatory support (MCS) or transplantation. Results A total of 37 VA-ECMO were managed in our Cardiac Intensive Care Unit (CICU) between January 2019 and March 2021. Most frequent aetiologies are reflected in table 1. Ventricular unloading was accomplished in 62.2% (23). We included four phases in our weaning protocol as described in figure 1. Second phase was used to select patients who could benefit from levosimendan infusion. This group included patients who accomplished the following criteria: appropriate aetiological treatment of shock, tolerance for 50% VA-ECMO flow reduction, noradrenaline dose <0,5 ug/kg/min, inotropic score <10 and correction of blood lactate, kidney and liver function parameters. Levosimendan was administered in 62.2% (23). 5 patients (13.5%) were not considered candidates to benefit from levosimendan (2 of them had early systolic function recovery and 3 patients seemed to have no chance to recover). Average time from VA-ECMO implantation to levosimendan infusion was 3.6 days, with a medium dose of 0,1 ug/kg/min. Norepinephrine medium dose was 0,12 mg/kg/min, with a medium inotropic score of 3 and vasoactive-inotropic score of 16,1. Levosimendan infusion did not cause any major side effects and was well tolerated by entire cohort even though norepinephrine dose had to be slightly increased in some cases. Whole sample procedural success rate reached 64.9% (24) whereas weaning rate from VA-ECMO without further support was 51.4% (19). 5 patients were upgraded to another MCS and 4 of them survived after transplantation. The subgroup which meets inclusion criteria to levosimendan reached a procedural success rate of 82.6% (19) and a weaning rate of 73.9% (19). Differences between patients with and without levosimendan treatment were statistically significant (procedural success rate: 82.6% vs 35.7%, p 0.006, weaning rate: 73.9% vs 14.3%, p<0.001). Meanwhile there were no significant differences regarding in-hospital mortality rate: 47.8% (11) vs 71.4% (10), p 0.160, even though there was a downward trend in levosimendan treated patients. Most frequent causes of death are shown in table 1. Only 3 patients died due to cardiac failure (1 was rejected for cardiac surgery and 2 were not candidates to other advanced therapies). Conclusions Standardized levosimendan infusion as part of VA-ECMO weaning protocol could enhance myocardial recovery and significantly increase procedural success rate. Randomized or propensity score matching studies would be desirable to prove this hypothesis. Funding Acknowledgement Type of funding sources: None. Table 1Weaning protocol

Abstracts of the 30th Annual Pediatric Pharmacy Association (PPA) Meeting April 21 to 25, 2021

Abstracts of the 30th Annual Pediatric Pharmacy Association (PPA) Meeting April 21 to 25, 2021

Preliminary Safety and Efficacy Data for Combined Checkpoint Inhibition with Ipilimumab (I) and Nivolumab (N) As Consolidation Following Autologous Stem Cell Transplantation (ASCT) for High-Risk Hematologic Malignancies - Cpit-001 Trial

Preliminary Safety and Efficacy Data for Combined Checkpoint Inhibition with Ipilimumab (I) and Nivolumab (N) As Consolidation Following Autologous Stem Cell Transplantation (ASCT) for High-Risk Hematologic Malignancies - Cpit-001 Trial

Impact of rapid infliximab infusions on access at a large academic tertiary medical center.

Infliximab promotes remission in patients with inflammatory bowel disease (IBD) and rheumatologic disease (RD). Rapid infliximab infusions (RI) reduce infusion time from 2 hours to 1 hour and can enhance access to care, as defined by capacity, safety, and patient characteristics. Our hypothesis for the study described here was that use of RI can enhance access for patients. Data on all patients receiving infliximab for IBD or RD at our outpatient infusion center from February 2016 to August 2017 were retrospectively analyzed. Demographic and clinical information were collected. Of 348 patients who received infliximab, 205 had IBD and 143 had RD. In terms of capacity, 40% of patients received RI, resulting in a 16.1% decrease in average daily infusion time and a 9.8% increase in average daily available scheduled infusion chair time (P = 0.720). In terms of safety, 4 patients switched back to standard infusions after RI, after 3 specifically had reactions to RI. In terms of patient characteristics, more patients with RD versus IBD received RI (P = 0.020). Among the patients with RD, a lower proportion receiving RI were female (P = 0.043). For the patients with IBD, a higher proportion receiving RI were White (P = 0.048). Among both patients with RD and patients with IBD, a higher proportion receiving RI had private insurance (P = 0.016 and P = 0.018, respectively). RI were safe and increased available chair time. Females with RD, patients of non-White race with IBD, and patients with public insurance were less likely to receive RI. Future directions include patient surveys and evaluation of implicit bias against patient factors that may impact access to RI.

Final results of a phase 1b study of isatuximab short-duration fixed-volume infusion combination therapy for relapsed/refractory multiple myeloma

Part B of this phase 1b study (ClinicalTrials.gov number, NCT02283775) evaluated safety and efficacy of a fixed-volume infusion of isatuximab, an anti-CD38 monoclonal antibody, in combination with pomalidomide and dexamethasone (Pd) in relapsed/refractory multiple myeloma patients. Isatuximab (10 mg/kg weekly for 4 weeks, then every other week) was administered as a fixed-volume infusion of 250 mL (mL/h infusion rate) with standard doses of Pd on 28-day cycles. Patients (N = 47) had a median of three prior treatment lines (range, 1–8). Median duration of exposure was 36.9 weeks and median duration of first, second, and 3+ infusions were 3.7, 1.8, and 1.2 h, respectively. The most common non-hematologic treatment-emergent adverse events were fatigue (63.8%), infusion reactions (IRs), cough, and upper respiratory tract infection (40.4% each). IRs were all grade 2 and occurred only during the first infusion. The overall response rate was 53.2% in all patients (55.5% in response-evaluable population, 60.0% in daratumumab-naïve patients). Efficacy and safety findings were consistent with data from the isatuximab plus Pd infusion schedule in Part A of this study and also from the phase 3 ICARIA-MM study, and these new data confirm the safety, efficacy, and feasibility of fixed-volume infusion of isatuximab.

P532 Delay of maintenance infliximab increases the risk of relapse in Crohn’s disease during the COVID-19 pandemic

BackgroundScheduled maintenance infliximab (IFX) therapies were frequently delayed during the COVID-19 pandemic. The unusual situation allowed us to study the influence of decreased treatment adherence on Crohn’s disease (CD). This retrospective study aimed to evaluate the effect of IFX delay on relapse in Crohn’s disease (CD) patients.Methods166 CD patients with maintenance IFX between January 25, 2020, and April 25, 2020, were retrospectively enrolled. Demographic and clinical characteristics were recorded. Relapse was defined as clinical disease relapse or biochemical disease relapse (C-reactive protein (CRP) level ≥5 mg/L without other, non-IBD related explanation). Associations between relapse and IFX delay were analyzed. ResultsA retrospective cohort study was conducted, including 166 CD patients receiving maintenance IFX infusion during the COVID-19 pandemic. Of all, 135 (81.3%) had delayed their IFX infusion. Only 31 (18.7%) followed the schedule infusion during the COVID-19 pandemic. The median time of the IFX delay was 18.6±17.1 days. The relapse rate in the IFX-delay group was significantly higher than the group without delay (25.9% versus 5.5%, P＜0.02). During a median IFX delay interval of 46 days (95% CI 20.9–71.1), the ratio of relapse increased with the increase of IFX delay intervals. Delay interval had a cumulative effect on disease recurrence. We proposed interval prolongation resulted in asignificant IFX trough concentration reduction. ConclusionOur study provided real-world evidence of influence on relapse of IFX delay in CD patients undergone maintenance therapy. It might help the IBD specialists arrange reasonable IFX treatment intervals for patients.

Biologically optimized schedule of gemcitabine and nab-paclitaxel regimen in metastatic pancreatic adenocarcinoma.

TPS4168 Background: Metastatic pancreatic adenocarcinoma has a poor prognosis, and improvements in therapy have been challenging. Alongside efforts in developing novel agents, there is a need to optimize and maximize the benefit of currently approved drugs. Gemcitabine + nab-paclitaxel is a frequently used regimen for pancreatic adenocarcinoma. Nab-paclitaxel is albumin–bound chemotherapy; hence the role of albumin uptake is critical for its effect. Caveolae are small membrane invaginations essential for transendothelial albumin uptake. Cav-1 is the principal structural component of caveolae. Williams and colleagues have published a series of preclinical studies demonstrating that tumor cell-specific Cav-1 expression directly correlates with albumin and albumin-bound chemotherapy uptake and subsequent apoptotic response in tumor cells. In vitro studies showed that exposure of pancreatic cancer cells to Gemcitabine resulted in up-regulation of Cav-1 peaking 48 hours after gemcitabine exposure. This Cav-1 up-regulation correlated with increased temporal albumin cellular uptake. In addition, Williams and colleagues noted that exposure of pancreatic cancer cell lines to Gemcitabine resulted in a time–specific re-entry of cells into the G2/M phase (nab-paclitaxel cytotoxicity phase) between 48-60 hours after gemcitabine treatment. Collectively this data suggest that infusing nab-paclitaxel after 48 hours of gemcitabine infusion would be optimal for both increased uptake as well as increased susceptible tumor cells. We had previously shown this effect on multiple cell lines as well as mouse models. Methods: This is a phase II trial; patients will receive a standard of care chemotherapy regimen consisting of FDA-approved Gemcitabine + nab-paclitaxel with modification of the schedule to deliver nab-paclitaxel 48 hours (2 days) after gemcitabine infusions. The primary endpoint is ORR, with a null hypothesis of 20% vs. a target of 35%. Employing a 2-stage design (minimax) and assuming 80% power and a 0.05 significance level, a total of 53 patients will be required. In the first stage, if at least 7/31 patients respond to therapy, an additional 22 patients will be added for a total of 53 patients. The study will be terminated early if ≤ six patients respond in the first stage. Observation of response in at least 16/53 patients would be required to warrant further investigation of this infusion schedule of combination therapy. The secondary endpoints include the safety of the regimen schedule, Relative dose intensity, disease control rate, PFS, and OS. The trial opened to enrollment in June 2020 and is accepting patients. Clinical trial information: NCT04115163.

Personalizing ocrelizumab treatment in Multiple Sclerosis: What can we learn from Sars-Cov2 pandemic?

During SARS-CoV-2 pandemic, we adopted a personalized delayed protocol for ocrelizumab infusions in Relapsing Remitting Multiple Sclerosis (RRMS) patients according to the national recommendations. Out of the 83 RRMS patients whose infusion was scheduled between March and December 2020, 56 patients experienced a delay in treatment based on MS severity and SARS-CoV2 infection risk profile. In most cases, the immunophenotype was performed monthly to guide re-infusions. Specifically, B CD19 + cells repopulation rate was monitored. Mean infusion delay was 103,1 [SD 40,6] days, and none of the patients presented relapses or active disease at MRI at the end of the observation period. Treatment naïve status and the interval between immunophenotyping and the last ocrelizumab infusion were predictors of earlier B CD19 + cells repopulation. Two patients contracted SARS-CoV2 with complete recovery. Definitive data about Sars-Cov2 vaccine efficacy in patients treated with ocrelizumab are still lacking. Our findings suggest that a personalized treatment with a delayed infusion schedule does not compromise ocrelizumab short-term efficacy and may help to lengthen the therapeutic window for an effective response to SARS-CoV2 vaccine.

Financial Toxicity as an Unforeseen Side Effect of Inflammatory Bowel Disease

A 32-year-old male with a history of ulcerative colitis diagnosed at age 26 presented to our emergency department with an episode of bloody diarrhea, marked abdominal cramping, subjective fever, and nausea. Work-up, including the consideration of an infectious cause, revealed an acute ulcerative colitis flare, with severe proctocolitis visualized with flexible sigmoidoscopy. He had no other past medical history besides tobacco use, for which he was recently “cutting back.” Further history elicited that he had been experiencing acute flares 2-3 times per year since his diagnosis, which caused many missed days from his work as a waiter and loss of vacation time. At one point, he was let go from a job due to these missed days and subsequently went temporarily without insurance. He had planned to begin stepped up treatment with biologics at the time, but could no longer afford it. In total, he accumulated around $10,000 in debt for his medical expenses. By this current admission, he had secured a new job, for which he was to begin before this flare prevented him from doing so. He was given IV steroids and supportive care, and ultimately discharged with an oral steroid taper and scheduled infliximab infusions.

Intracellular vincristine levels in lymphoblasts affect treatment outcome in childhood B‐lymphoblastic leukaemia: Ma‐Spore ALL 2010 study

Vincristine (VCR) is a key drug in the successful multidrug chemotherapy for childhood acute lymphoblastic leukaemia (ALL). However, it remains unclear how VCR pharmacokinetics affects its antileukaemic efficacy. The objective of this study is to explore the VCR pharmacokinetic parameters and intracellular VCR levels in an up-front window of Ma-Spore ALL 2010 (MS2010) study. We randomised 429 children with newly diagnosed ALL to 15-minute vs 3-hour infusion for the first dose of VCR to study if prolonging the first dose of VCR infusion improved response. In a subgroup of 115 B-ALL and 20 T-ALL patients, we performed VCR plasma (n = 135 patients) and intracellular (n = 66 patients) pharmacokinetic studies. The correlations between pharmacokinetic parameters and intracellular VCR levels with early treatment response, final outcome and ABCB1 genotypes were analysed. There was no significant difference between 15-minute and 3-hour infusion schedules in median Day 8 peripheral or bone marrow blast response. Plasma VCR pharmacokinetic parameters did not predict outcome. However, in B-ALL, Day 33 minimal residual disease (MRD) negative patients and patients in continuous complete remission had significantly higher median intracellular VCR24h levels (P = .03 and P = .04, respectively). The median VCR24h intracellular levels were similar among the common genetic subtypes of ALL (P = .4). Patients homozygous for wild-type ABCB1 2677GG had significantly higher median intracellular VCR24h (P = .04) than 2677TT. We showed that in childhood B-ALL, the intracellular VCR24h levels in lymphoblasts affected treatment outcomes. The intracellular VCR24h level was independent of leukaemia subtype but dependent on host ABCB1 G2677T genotype.

Long-Term Safety of Rapid Daratumumab Infusions in Multiple Myeloma Patients.

Multiple myeloma survival has significantly improved in recent years, due to novel agents that are available for treatment. The anti-CD38 monoclonal antibody Daratumumab is particularly efficient for patients with relapse/refractory disease, and many studies have shown its unprecedented efficacy also as a first treatment. However, to avoid the incidence of infusion reactions, long infusion schedules of 8 h at first dose and 4 h in the following doses are required, which can reduce the compliance of patients and health care professionals. A reduced infusion time of 90 min has been reported previously, but data are missing on the prolonged safety of this over time as well as the efficacy of this approach. In this work, we investigate the safety of 484 rapid Daratumumab infusions given early after the second dose over a 22 months period in 39 myeloma patients.

Silicone oil: physical properties and clinical use (a literature review)

Introduction. In modern vitreoretinal surgery, silicone oil is used for replacing the vitreous body during vitrectomy. This surgery is performed to treat retinal detachment, proliferative retinopathy, giant retinal tears and severe eye injuries. In this regard, it seems especially relevant to provide a description of the physical characteristics of silicone oils that determine the choice of surgeons.Purpose. To study indications for the use of silicone oil tamponade as well as possible complications associated with its use based on a literature review and own research.Materials and methods. We analyzed literature on PubMed, eLibrary, and Medline over the past 30 years. Overall, 34 sources of literature were reviewed, including results of our own clinical studies.Results. Literature review has shown that silicone oils are very useful as a permanent tamponade. Although gas tamponade can be used for giant retinal tear management, silicone oils are used for minimizing the risk of post-surgical bleeding and reattach detached retinas in case of severe eye injuries. One of the main issues related to the use of silicone oils is the post-surgical increase in IOP. To reduce the risk of such complication, we have proposed methods of infusion and optimal schedule of silicone oil removal.Conclusion. Silicone oil is the optimal choice for treating most retinal diseases and improving their prognosis. An important criterion for choice of silicone oil is the time that is required for tamponade.

Partially mismatched pediatric transplants with allogeneic CD34^+ blood cells from a related donor

This was a phase I, multi-center study of 13 pediatric patients (median age, 11 years) to evaluate toxicity, hematopoietic recovery, and graft-versus-host disease (GVHD) after allogeneic transplantation of enriched blood CD34(+) cells obtained from genotypically haploidentical but partially HLA-mismatched related donors (8 parents and 5 siblings). With regard to rejection, donor HLA disparity was 1 (5), 2 (6), or 3 loci (2). With regard to GVHD, recipient HLA disparity was 0 (1), 1 (3), 2 (8), or 3 (1). The patients suffered from acute myelogenous leukemia (6), chronic myelogenous leukemia (4), acute lymphoblastic leukemia (2), or hemolytic anemia plus immunodeficiency disorder (1). To reduce the risk of graft failure through the infusion of a large amount of stem cells, peripheral blood cells (PBC) were mobilized by recombinant granulocyte colony-stimulating factor (G-CSF; lenograstim, 10 microgram/kg/d for 5 days) and collected by 2 to 5 aphereses. To both enhance engraftment and reduce GVHD, CD34(+) cells were enriched using immunomagnetic procedures with the Baxter ISOLEX 300 system (Baxter Healthcare Corp, Irvine, CA) and cryopreserved. After variable cytoreductive regimens, a median of 7.7 (range, 2.2 to 14) x 10(6)/kg of CD34(+) cells and 1.03 (0.05 to 2.09) x 10(5)/kg CD3(+) cells were infused. Using Center-specific posttransplant supportive care and immunosuppressive GVHD prophylaxis, two patients experienced early death; one from veno-occlusive disease at day 17 and one from sepsis at day 18. Nine of 11 patients showed signs of engraftment; however, subsequent rejection was seen in 4 patients, 2 of whom had autologous recovery. Eight patients were evaluated in the early phase of marrow recovery. The median number of days to achieve an absolute granulocyte count of 0.5 x 10(9)/L was 14 (range, 9 to 20) and that to achieve a platelet count of 20 x 10(9)/L was 17.5 (range, 12 to 23). Donor chimerism persisted in five patients until death or current survival. All of the surviving patients with functioning-donor-type hematopoiesis were given total body irradiation. De novo acute GVHD (grades II and IV) was observed in two of the eight evaluated patients. Scheduled donor lymphocyte infusion (DLI), using the CD34(-) fraction, was administered to four patients, free of de novo acute GVHD, beginning between 28 to 43 days after transplant. Three of these patients developed acute GVHD (grades I, II, and IV). Cytomegalovirus infection was a major infectious complication but was successfully managed with gamma-globulin and gancyclovir treatment with or without additional DLI. Five patients are currently surviving, free of disease, with a follow-up ranging from 476 to 937 days. Each survivor has functioning hematopoiesis, three of donor origin and two of autologous origin. In conclusion, our results show that enriched blood CD34(+) cells from a mismatched haploidentical donor are a feasible alternative source of stem cells, but do not appear to ensure engraftment. Because none of the patients who were administered DLI survived, the therapeutic efficacy and safety of periodic DLI, as an integrated part of such transplants, needs to be clarified in further studies.

Trial in Progress: A Prospective Phase I/II Trial to Jointly Optimize the Administration Schedule(s) and Dose(s) of Melphalan for Injection (Evomela) As a Preparative Regimen for Autologous Hematopoietic Stem Cell Transplantation in Newly Diagnosed Multiple Myeloma

Background: High-dose chemotherapy followed by autologous hematopoietic cell transplantation (auto HCT) is considered to be the standard of care treatment for transplant-eligible patients with multiple myeloma (MM). The most commonly used conditioning regimen in this setting is high-dose melphalan by intravenous administration. Conventional melphalan formulations, when administered at high doses, can put patients at risk of potential propylene glycol-associated toxicities. Melphalan for injection (Evomela) is propylene glycol free (PGF), can be dissolved directly using saline, and as a PGF reformulation of Alkeran, incorporating Captisol brand of beta-cyclodextrin sulfobutyl ethers sodium salts, overcomes previous formulation limitations. In 2016 Evomela was the first product approved by the US FDA for high-dose conditioning treatment prior to HCT in MM patients and it is also indicated for the palliative treatment of patients with MM for whom oral therapy is not appropriate. Reconstituted Evomela solution can be stored in the vial for up to 1 hour at room temperature or up to 24 hours at 2-8 °C with no significant degradation. After storage in the vial, it remains stable for an additional 3 to 29 hours after, preparation of admixture solution in infusion bags at concentrations of 0.25 to 5.0 mg/mL, respectively. As well, Evomela solution in saline, at concentration of 5.0 mg/mL melphalan, was bacteriostatic through 72 hours when stored at 2-8 °C. This stability allows for less frequent handling by pharmacy and nursing staff, resulting in a concomitant decrease in exposure risks, increased convenience and administration flexibility, suggestive of an improved ease of handling and administration, when compared to Alkeran. Further, Evomela may actually be less toxic due to the absence of propylene glycol. Although increased melphalan doses have previously demonstrated signals of improved response, the most commonly used dose of melphalan is 200 mg/m2, primarily due to concerns of toxicity. Emerging data regarding higher stability and potentially less toxicity of PGF melphalan (Evomela) supports dose escalation evaluation in order to improve the outcomes. Previous trial data have shown that continuous infusion or frequent fractionated-dose delivery increases the antitumour activity of several drugs. Due to the instability of currently available Alkeran at the room temperature, infusional studies have not been feasible. This limitation is overcome by Evomela, being that the compound is stable for several hours at the room temperature, thus allowing evaluation of infusional schedules in addition to the traditional 30-60 minute bolus doses. Here, we describe a trial designed to assess whether the above noted characteristics of Evomela allow for the escalation of dose and prolongation of infusion time, in order to increase the efficacy of melphalan in patients undergoing auto-HCT. Study Design/Methods: This is a two-stage phase I-II trial to optimize the dose and schedule of Evomela given as a single agent preparative regimen for auto-HCT. Up to 60 participants may be included if they are 18-70 years of age, with non-relapsed MM, have a Karnofsky performance score ≥70%, who have received at least two cycles of initial systemic therapy, and are within 2 to 12 months of the first dose. Patients will be randomized 1:1 to two different infusion schedules (30-60 minute infusion or 8-9 hour infusion) using Evomela (2mg/ml) at two dose cohorts (200mg/ml2 or 225mg/m2). Because 2 mg/mL Evomela is stable for 10 hours, patients receiving the 8-9 hour infusion will receive the total dose in one single infusion bag. The primary objectives are to determine the optimal dose and schedule of Evomela before auto-HCT for MM and collect pharmacokinetic data and compare the exposure-response evaluations between the two infusion schedules. Secondary outcomes will include incidence of treatment-related mortality, rate of minimal residual disease negative complete response at 90 days post auto-HCT, progression-free survival and overall survival after auto-HCT in newly diagnosed myeloma patients treated on different schedules and doses of Evomela. The active study follow-up period will be up to one-year post auto-HCT. Figure Disclosures Bashir: Acrotech: Research Funding; StemLine: Research Funding; Takeda: Other: Advisory Board, Research Funding; Celgene: Research Funding; KITE: Other: Advisory Board; Amgen: Other: Advisory Board; Purdue: Other: Advisory Board. Qazilbash:Amgen: Research Funding; Bioclinica: Consultancy; Angiocrine: Research Funding; Bioline: Research Funding; Janssen: Research Funding.

Adherence and a Potential Trade-Off Currently Faced in Optimizing Hemophilia Treatment

INTRODUCTION Severe hemophilia, i.e., <1% normal FVIII level (A) or FIX level (B), are congenital bleeding disorders characterized by uncontrolled bleeding. The clinical benefits of prophylactic FVIII/IX replacement therapy are well understood, but require adherence to a schedule of routine infusions. Optimal adherence is associated with better joint outcomes and lower rates of chronic pain. Nonetheless a lack of patient-reported data has to date limited our understanding of the patient burden associated with adherence to treatment, and the relationship between adherence and the ability to work, among people living with hemophilia in the US. Data from the Bridging Hemophilia B Experiences, Results and Opportunities into Solutions (B-HERO-S) study reported a high proportion of adults with hemophilia B receiving routine infusions (at least one infusion per month), showing a negative impact on their ability to work, and people receiving routine infusions were more likely than people treated on-demand to report an inability to work in most situations. The ability of people living with hemophilia to participate in the labor force, without barriers to job choice or working hours, is a key outcome in the drive to achieve health equity. The objective of the analysis is to examine the relationship between adherence and the labor force participation of people with severe hemophilia in the US. METHODS This analysis draws data from a patient-reported study, the 'Cost of Severe Hemophilia Across the US: A Socioeconomic Survey' (CHESS US+). Conducted in 2019, the CHESS US+ study is a cross-sectional patient-centered study of adults with severe hemophilia in the US. A patient-completed questionnaire collected data on clinical, economic, and humanistic outcomes, for a 12-month retrospective period. This analysis examines labor force participation and employment status (full-time, part-time, unemployed, retired) and chronic pain categorized by 'none', low-level ('1-5'), and high-level ('6-10'). The analysis was stratified by adherence to treatment, self-reported on a 1-10 scale, from "not at all" to "fully", categorized into low (1-6), moderate (7-9) and full (10) adherence. Results are presented as mean (standard deviation) or N (%). RESULTS The analysis comprised 356 people with severe hemophilia A (73%) and B (27%) who participated in CHESS US+ study. In Table 1, the baseline characteristics of the study population are stratified by full adherence (N = 119), moderate adherence (N=134) and low adherence (N=103). Having no chronic pain was most prevalent in the full adherence group (37.7%), compared to moderate (8.3%) or low (13.9%) adherence cohorts. Chronic pain, both low- and high-levels were least prevalent among people with full adherence. Moreover, people with low adherence were disproportionately more likely to have high-levels of chronic pain relative to moderate adherence or full adherence (Table 1). Unemployment, however, was highest in full adherence (21.1%), and people with full adherence were also least likely to be in full-time employment (42%). The full-time employment rate decreased as adherence declined from full to moderate (Table 1), and was comparable in people with low adherence (57.3%) or moderate adherence (54.5%). CONCLUSIONS This analysis of CHESS US+ examined the complex relationship between labor market outcomes and adherence to treatment, among adults with severe hemophilia in the US. Adherence was associated with lower rates of chronic pain, representing the importance of achieving an optimal treatment strategy. Nonetheless, patients achieving optimal adherence were less likely to be in full-time employment, and more likely to be part-time or unemployed, comparatively. Together, these data characterize a trade-off in clinical outcomes versus workforce participation, and suggest that the goal of achieving health equity may currently still be unmet. Disclosures Burke: HCD Economics: Current Employment; University of Chester: Current Employment; F. Hoffmann-La Roche Ltd: Consultancy. Asghar:HCD Economics: Current Employment. Misciattelli:Freeline: Current Employment, Current equity holder in publicly-traded company. Kar:Freeline: Current Employment, Current equity holder in publicly-traded company. Morgan:uniQure: Consultancy; HCD Economics: Current Employment. Dhillon:HCD Economics: Current Employment; F. Hoffmann-La Roche Ltd: Other: All authors received editorial support for this abstract, furnished by Scott Battle, funded by F. Hoffmann-La Roche Ltd, Basel, Switzerland. . O'Hara:HCD Economics: Current Employment, Current equity holder in private company; F. Hoffmann-La Roche Ltd: Consultancy.

Adoptive Therapy with Allogeneic Cord Blood T Regulatory Cells Show Safety and Early Clinical Signal in Primary Myelofibrosis

Adoptive Therapy with Allogeneic Cord Blood T Regulatory Cells Show Safety and Early Clinical Signal in Primary Myelofibrosis

Intravenous Iron Infusion Administration Schedule and Hematologic Response; A Single-Center Retrospective Cohort Study

Background: Clinical trials studying the efficacy of intravenous (IV) iron replacement have used a variety of dosing schedules, even for the same iron formulations and there isn't a clear standard for how IV iron replacement should be scheduled. Differences in iron absorption efficiency have been observed with different oral iron supplementation schedules but it is not known if the same is true for IV iron. The objective of this study was to evaluate the association between iron administration schedule and hemoglobin response in patients treated at a tertiary care center. Methods: Data was collected retrospectively using The Ottawa Hospital Data Warehouse (OHDW) capturing all iron infusions given at 3 local institutions between January 2007 and December 2018. Patients that received at least 2 intravenous iron infusions within 180 days of each other were included. A 'course' of iron replacement was defined as consecutive infusions with ≤180 days between doses. Patients transfused red blood cells within 90 days of the last iron infusion in each course were excluded. Patient age, sex, dose and formulation of administered, date of each iron infusion, and laboratory parameters from the period starting 3 months before the first infusion to 6 months after the last infusion were extracted for analysis. Patients were categorized into 4 groups based on the mean time between iron infusions in each course: 1-10 days, 11-20 days, 21-30 days, and >30 days. Achieving a maximum hemoglobin (Hb) 10 g/L or higher than the pre-infusion Hb was defined as a 'good' response. A logistic regression model was used to evaluate the association between interval between infusions and achieving a 'good' Hb response. The model was adjusted for sex, age, presence of chronic kidney disease (CKD), dose of iron per course, number of infusions per course, and number of courses. CKD was defined as having a serum creatinine >177 µmol/L. Iron sucrose, iron gluconate, and iron dextran were available for administration during the study period. Results: A total of 4350 patients were included in the analysis. These patients received a total of 6409 courses of iron replacement, with a median of 2 courses (interquartile range [IQR] 1-3) per patient, and 4 infusions (IQR 3-6) per replacement course. Infusions were given a median of 21.9 days (IQR 12-34) apart in each course, with a range of 1-179 days. Iron sucrose was given in most courses (81.6%), followed by iron gluconate (18.2%) and iron dextran (0.1%). Patient characteristics are summarized in Table 1 and laboratory values prior to the first infusion of each course are summarized in Table 2. The interval between iron infusions was associated with Hb response. Results of the logistic regression are summarized Table 3. Compared with patients receiving infusions every 10-20 days, patients receiving infusions more frequently or less frequently were less likely to achieve a good Hb response. Male sex was associated with increased odds of response, while increasing age, having CKD, and receiving more courses of iron were associated with decreased odds of response. Conclusions: In this single-center retrospective cohort analysis, an association between interval of iron infusions and hematologic response was observed. Patients given iron every 10-20 days more likely to achieve a good response compared with more, or less frequent dosing intervals. Strengths of this study include the large sample size, adjustment for sex, age, presence of CKD, and number of iron infusions and courses given. Transfused patients were excluded, so the hemoglobin response is attributable to iron replacement. The study has several important limitations. The clinical decision-making for the infusion schedule was not known and factors that went into this decision are a possible source of confounding (for example, ongoing bleeding). The suspected cause of iron deficiency was not known. Additionally, concomitant oral iron supplementation and iron infusions or transfusions occurring outside the study institution are unknowns and may influence to outcome. The hypothesis-generating findings suggest that the schedule of iron administration may play an important role in hematologic response to iron infusions. Disclosures No relevant conflicts of interest to declare.