High dose valacyclovir for cytomegalovirus prophylaxis following allogeneic hematopoietic cell transplantation.

INTRODUCTION: Cytomegalovirus (CMV) is one of the most common and clinically significant viral infections following allogeneic hematopoietic cell transplantation (HCT). Currently available options for CMV prophylaxis and treatment present challenges related to side effects and cost. METHODS: In this retrospective medical record review, the incidence of clinically significant CMV infection (CMV disease or reactivation requiring preemptive treatment) following allogeneic HCT was compared in patients receiving valacyclovir 1 g three times daily versus acyclovir 400 mg every 12 h for viral prophylaxis. RESULTS: Forty-five patients who received valacyclovir were matched based on propensity scoring to 35 patients who received acyclovir. All patients received reduced-intensity conditioning regimens containing anti-thymocyte globulin. Clinically significant CMV infection by day + 180 was lower in the valacyclovir group compared to the acyclovir group (18% vs. 57%, p = 0.0004). Patients receiving valacyclovir prophylaxis also had less severe infection evidenced by a reduction in CMV disease, lower peak CMV titers, delayed CMV reactivation, and less secondary neutropenia. CONCLUSION: Prospective evaluation of valacyclovir 1 g three times daily for viral prophylaxis following allogeneic HCT is warranted. Due to valacyclovir's favorable toxicity profile and affordable cost, it has the potential to benefit patients on a broad scale as an option for CMV prophylaxis.

American Society for Blood and Marrow Transplantation Pharmacy Special Interest Group Survey on Chimeric Antigen Receptor T Cell Therapy Administrative, Logistic, and Toxicity Management Practices in the United States.

Administration of immune effector cell (IEC) therapy is a complex endeavor requiring extensive coordination and communication of various healthcare and administrative teams. Chimeric antigen receptor (CAR) T cells are the most established IEC therapy available. As of July 2018 two commercial gene therapy products, tisagenlecleucel and axicabtagene ciloleucel, have been approved by the US Food and Drug Administration. To gain insight into the infrastructure and practices across the country, the American Society for Blood and Marrow Transplantation Pharmacy Special Interest Group conducted an electronic survey on the current administrative, logistic, and toxicity management practices of CAR T cell therapy across the United States. This survey consists of 52 responses from institutions of varying sizes, most of which (∼80%) had previous investigational experience with CAR T cell therapy. Absorbing the energy of this exciting new treatment has challenged hematopoietic cell transplant programs across the country to strengthen department infrastructure, develop new committees and policies, and implement significant education to ensure safe administration. With the variety of experience with CAR T cell therapy, we hope this survey can contribute to the existing published literature and provide support and consensus to established and developing IEC programs and practice guidelines.

Evaluation of empiric antibiotic de-escalation in febrile neutropenia.

INTRODUCTION: Up until 2010, the recommended duration of empiric broad-spectrum antibiotics for febrile neutropenia was until absolute neutrophil count (ANC) recovery. An updated guideline on the use of antimicrobial agents in neutropenic patients with cancer indicates that patients who have completed an appropriate treatment course of broad-spectrum antibiotics, with resolution of signs and symptoms of infection but persistent neutropenia, can be de-escalated to oral fluoroquinolone prophylaxis until ANC recovery. METHODS: The primary objective of this retrospective investigation was to evaluate the safety and efficacy of de-escalating broad-spectrum antibiotics in patients remaining neutropenic after at least 14 days of empiric broadspectrum antibiotics for febrile neutropenia compared to patients continuing broad-spectrum antibiotics until ANC recovery. RESULTS: There were 16 patients (61.5%) in the comparator group who met the primary endpoint of remaining afebrile and without escalation of antibiotics for at least 72 hours after 14 days of broad-spectrum antibiotics and 21 patients (80.7%) in the de-escalation group who met the primary endpoint of remaining afebrile and without reinitiation of broad-spectrum antibiotics for at least 72 hours after de-escalation to levofloxacin therapy (p = 0.11). Mean total duration of broad-spectrum antibiotic therapy was 23.5 ± 1.5 days in the comparator group versus 22.2 ± 1.43 days in the de-escalation group (p = 0.39). CONCLUSIONS: Results of this investigation indicate that broad-spectrum antibiotics can be safely de-escalated to levofloxacin prophylaxis prior to ANC recovery in select patients. This practice may decrease the duration of broad-spectrum antibiotic exposure and associated complications.

Real-world experience with clinical management of talquetamab in relapsed/refractory multiple myeloma: a qualitative study of US healthcare providers.

OBJECTIVE: Talquetamab is the first-in-class GPRC5DxCD3 bispecific antibody for relapsed/refractory multiple myeloma. Given limited real-world data, this study was conducted with US healthcare providers (HCPs) to understand real-world talquetamab dosing and symptom management. METHODS: In February/March 2024, individual in-depth interviews (IDIs; n = 10) were conducted with HCPs administering talquetamab in real-world settings. A subsequent expert panel (n = 6) further discussed current practices. RESULTS: The IDIs reported a variety of settings for step-up dosing (SUD), including inpatient (n = 5), outpatient (n = 3), and hybrid models (n = 2), with a trend toward shorter SUD length to reduce healthcare resource utilization. Most HCPs used a biweekly (Q2W) schedule in SUD (n = 7) and treatment phases (n = 8). Six participants explored reducing dose frequency to every 4 weeks (Q4W) in patients following positive disease response to treatment, considering patient convenience and relieving GPRC5D-related symptoms. Panelists recommended symptom management and prophylactic strategies, such as dexamethasone and nystatin mouthwash or zinc and vitamin B complex for oral symptoms, and topical steroids and cosmetic products for skin and nail symptoms. CONCLUSION: This study outlines current real-world practices for talquetamab. Findings indicate variation in the SUD care setting. The 0.8 mg/kg Q2W dosing schedule was most common, although switching to Q4W is a real-world symptom management strategy for some patients with responses to therapy. GPRC5D-related symptom management approaches are evolving; prophylactic use of dexamethasone and nystatin mouthwash or zinc and vitamin B complex may be effective strategies to alleviate oral symptoms. Further real-world evidence is needed to inform optimal dosing schedules while mitigating symptom impact.

Talquetamab is a new treatment that was approved in the United States in 2023 for a type of blood cancer called multiple myeloma. This drug is administered at one of two doses, each of which includes a defined step-up dosing schedule where patients first receive smaller amounts of the drug to help avoid serious side effects. Because talquetamab is new and associated with treatment-related symptoms not normally seen with other multiple myeloma treatments, doctors and patients need more guidance on drug administration and symptom management. In this study, we describe findings from interviews and an expert panel discussion with healthcare professionals who have experience using talquetamab. This study found that most healthcare professionals administered step-up dosing with patients staying overnight in the hospital, while other providers administered these doses during outpatient visits. Most providers administered talquetamab once every 2 weeks after utilizing the associated step-up dosing schedule. Additionally, healthcare providers described transitioning some patients, who had responded positively to treatment, to a less frequent dosing schedule of once per month to help reduce the effect of treatment-related symptoms. Participants in the expert panel described approaches for managing or preventing these symptoms, such as dexamethasone and nystatin mouthwashes or zinc and vitamin B complex for oral symptoms, and topical steroids and cosmetic products for skin and nail symptoms. In summary, this study provides valuable real-world information from healthcare providers who have experience treating patients with multiple myeloma with talquetamab.

Dynamical Systems Modeling of Early-Term Immune Reconstitution with Different Antithymocyte Globulin Administration Schedules in Allogeneic Stem Cell Transplantation.

Alloreactivity forms the basis of allogeneic hematopoietic cell transplantation (HCT), with donor-derived T cell response to recipient antigens mediating clinical responses either in part or entirely. These encompass the different manifestations of graft-versus-host disease (GVHD), infection risk, and disease response. While the latter is contingent on disease biology and thus may be less predictable, the former 2 manifestations are more likely to be directly proportional to the magnitude of donor-derived T cell recovery. Herein we explore the quantitative aspects of immune cell recovery following allogeneic HCT and clinical outcomes in 2 cohorts of HLA-matched allograft recipients who received rabbit antithymocyte globulin (ATG) on different schedules (days -9 to -7 versus days -3 to -1). Monocyte as well as donor-derived T cell (ddCD3) recovery was superior in those given ATG early in the course of disease (days -9/-7). This difference was related to a more rapid rate of ddCD3 recovery, driven largely by CD3+/CD8+ cells in the first month post-transplantation. Early monocyte recovery was associated with later T cell recovery and improved survival. In contrast, rapid and early ddCD3 expansion out of proportion to monocyte recovery was associated with a high likelihood of acute GVHD and poor survival. This analytic methodology demonstrates that modeling "early-term immune reconstitution" following HCT yields insights that may be useful in the management of post-transplantation immunosuppression and adaptive cellular therapy to optimize clinical outcomes. © 2021 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.

Managing post allograft relapse of myeloid neoplasms: azacitidine and donor lymphocyte infusions as salvage therapy.

Azacitidine (Aza) may promote cytotoxic effects against hematologic tumor cells when combined with donor lymphocyte infusions (DLIs). This study sought to verify Aza-DLI's efficacy and tolerability in patients with relapsed acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) following allogeneic stem cell transplantation (SCT) and identify cohorts benefitting most from therapy. Twenty-eight patients with recurrent AML or MDS following SCT received Aza-DLI. One-year overall survival (OS) after therapy initiation was 44%; two-year OS was 35%. Molecular/cytogenetic-only relapse, the development of cGVHD after therapy initiation, and a greater number of Aza and DLI were associated with remission. There was a trend toward higher absolute CD4+ cell count in those achieving remission. This study demonstrates Aza-DLI to be effective and highlights the importance of minimal residual disease testing and alloreactivity in managing post allograft relapsed hematological malignancy.

Maintenance azacitidine after myeloablative allogeneic hematopoietic cell transplantation for myeloid malignancies.

Allogeneic hematopoietic cell transplantation (HCT) is a curative option for patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), but carries a high risk of relapse. This retrospective review evaluates the effectiveness of maintenance azacitidine in high-risk AML and MDS patients to reduce the probability of relapse. Twenty-five patients who received maintenance azacitidine were matched to historical controls in a two-to-one ratio based on diagnosis, donor type, conditioning regimen intensity, and age. Over 90% of patients received myeloablative conditioning. There was no difference in time to hematologic relapse, overall survival, or non-relapse mortality. Maintenance therapy was stopped early in 72% of patients due to graft-versus-host-disease, relapse, infection, and intolerance (13 of 25 patients received less than 4 cycles). There was a trend towards higher toxicity in the azacitidine group. The use of prophylactic azacitidine following myeloablative allogeneic HCT outside a clinical trial cannot be recommended at this time.

Intravenous Lidocaine as an Adjuvant for Pain Associated with Sickle Cell Disease.

The objectives of this study were to evaluate the efficacy and safety of adjuvant intravenous (IV) lidocaine in adults with sickle cell disease (SCD). This was a retrospective review. Adults with SCD receiving at least one IV lidocaine infusion from 2004 to 2014 were included. Patient demographics, lidocaine treatment parameters, pain scores, pain medications, and adverse effects were recorded. Eleven patients were identified, yielding 15 IV lidocaine trials. Clinical improvement in pain scores from pre-lidocaine challenge to 24 hours post-lidocaine challenge, defined by ≥ 20% reduction in pain scores, was achieved in 53.3% (8 of 15) of IV lidocaine challenges. Of the 8 clinically successful trials, the mean reduction in morphine dose equivalents (MDE) from 24 hours pre-lidocaine challenge to 24 hours post-lidocaine challenge was 32.2%. Additionally, clinically successful trials had a mean initial and a maximum dose of 1 mg/kg/h (range: 0.5-2.7 mg/kg/h) and 1.3 mg/kg/h (range: 0.5-1.9 mg/kg/h), respectively. On average, these patients underwent 3 dose titrations (range: 1-8) and received lidocaine infusions for 4.4 days (range: 2-8 days). Two patients experienced disorientation and dizziness. The authors conclude that adjuvant IV lidocaine provided pain relief and a mean reduction in MDE during sickle cell pain crisis. These results provide preliminary insight into the use of IV lidocaine for treating pain in patients with SCD, although prospective studies are needed to determine efficacy, dosing, and tolerability of IV lidocaine in this patient population.