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Cord blood transplantation (CBT) is curative for many patients with hematologic malignancies but is associated with delayed immune recovery and an increased risk of viral infections compared to human leukocyte antigen (HLA) matched bone marrow or peripheral blood progenitor cell transplantation. In this study we evaluated the significance of lymphocyte recovery in 125 consecutive patients with hematologic malignancies who underwent double-unit CBT (DUCBT) with an anti-thymocyte globulin-containing regimen at our institution. A subset of 65 patients were prospectively evaluated for recovery of T, natural killer (NK) and B cells and in 46 patients we also examined viral-specific T cell recovery against Adenovirus, Epstein-Barr virus, cytomegalovirus, BK virus, respiratory syncytial virus and Influenza antigen. Our results indicate that in recipients of DUCBT, the day 30 absolute lymphocyte count is highly predictive of non-relapse mortality (NRM) and overall survival (OS). Immune recovery post-DUCBT was characterized by prolonged CD8+ and CD4+ T lymphopenia associated with preferential expansion of B and NK cells. We also observed profound delays in quantitative and functional recovery of viral-specific CD4+ and CD8+ T-cell responses for the first year post-CBT. Taken together, our data support efforts aimed at optimizing viral-specific T cell recovery to improve outcomes post-CBT.

Advanced and metastatic squamous cell carcinomas (SCC) are common and difficult-to-treat malignancies. We assessed 75 immunotherapy-treated patients with SCC from a clinically annotated database of 2,651 patients, as well as 9,407 patients from a deidentified database for molecular features that might influence checkpoint blockade response. SCCs had higher tumor mutational burdens (TMB) than non-SCCs (P < 0.0001). Cutaneous SCCs had the highest TMB (P < 0.0001), with 41.3% demonstrating a very high TMB (!50 mutations/Mb). In immunotherapy-treated patients with SCC, higher TMB (!12 mutations/Mb) correlated with a trend to higher clinical benefit rate [stable disease ! 6 months or partial/complete remission; 60% vs. 29%; (high vs. low TMB); P ¼ 0.06] and significantly longer median time-to-treatment failure (TTF; 9.9 vs. 4.4 months; P ¼ 0.0058). Cutaneous SCCs had the highest clinical benefit [11/15 patients (73%) vs. 20/60 (33%) noncutaneous (P ¼ 0.008)], TTF (P ¼ 0.0015), and overall survival (P ¼ 0.06) with immunotherapy treatment. In conclusion, among a diverse set of SCCs, higher TMB and cutaneous disease associated with better immunotherapy outcome.

Antibodies targeting the PD-1, PD-L1, and CTLA-4 immune checkpoint axis have been used in a variety of tumor types. They achieve anti-tumor activity through activating the patient’s own immune system to target immune response evading cancer cells. However, this unique mechanism of action may cause immune-related adverse events, irAEs. One of these irAEs is myocarditis which is associated with an alarming mortality rate. In this study we presented clinical cases of myocarditis from safety trial datasets submitted to the U.S. Food and Drug Administration, FDA. Additionally, we analyzed over fourteen million FDA Adverse Event Reporting System, FAERS, submissions. The statistical analysis of the FAERS data provided evidence of significantly increased reporting of myocarditis in patients administered immune checkpoint inhibitors alone, in combination with another immune checkpoint inhibitor, the kinase inhibitor axitinib, or chemotherapy, for all cancer types, when compared to patients administered chemotherapy. All combination therapies led to further increased reporting odds ratios of myocarditis. We further analyzed the occurrence of myocarditis by stratifying the reports into sub-cohorts based on specific cancer types and treatment/control groups in major cancer immunotherapy efficacy trials and confirmed the observed trend for each cohort.

Introduction: The scope of pharmacy practice has evolved over the last few decades to focus on the optimization of medication therapy. Despite this positive impact, the lack of reimbursement remains a significant barrier to the implementation of innovative pharmacist practice models. Summary: We describe the successful development, implementation and outcomes of three types of pharmacist collaborative care models: (1) a pharmacist with physician oversight, (2) pharmacist–interprofessional teams and (3) physician–pharmacist teams. The outcome measurement of these pharmacist care models varied from the design phase to patient volume measurement and to comprehensive quality dashboards. All of these practice models have been successfully funded by affiliated health systems or grants. Conclusions: The expansion of pharmacist services delivered by clinical faculty has several benefits to affiliated health systems: (1) significant improvements in patient care quality, (2) access to experts in specialty areas, and (3) the dissemination of outcomes with national and international recognition, increasing the visibility of the health system.

Background Current workforce shortages within the hematopoietic stem cell transplant field necessitate capitalizing on the role of oncology-trained pharmacists. Working within an agreed-upon protocol, pharmacists are able to expand patient care delivery through optimal medication therapy management. Methods An electronic survey was developed by the Advocacy & Policy Working Committee of the American Society for Blood and Marrow Transplantation Pharmacy Special Interest Group and distributed to pharmacists involved in the care of hematopoietic stem cell transplant patients. The primary objective was to assess the current state of collaborative practice agreements in the hematopoietic stem cell transplant setting. Results Forty-eight responses representing 41 institutions were returned. Respondents were mostly female (67%) and practiced in the adult setting (83%). Reponses represented a range of practice experience in hematopoietic stem cell transplant with the majority of the hematopoietic stem cell transplant positions (83%) funded by the department of pharmacy at an academic medical center. Of the 48 responses, 22 (46%) respondents reported having collaborative practice agreements in place; 10 (21%) respondents did not currently have collaborative practice agreements, but were planning to implement them; and 16 (33%) respondents did not have collaborative practice agreements at their institution. Clinical activities performed under a collaborative practice agreement included medication selection and dosing modifications, therapeutic drug monitoring, supportive care management, and management of comorbid conditions and chronic diseases. The most commonly cited barrier to establishing collaborative practice agreements was the inability to secure reimbursement for services provided. No respondents reported a negative impact on job satisfaction. Conclusions The results of this survey provide the pharmacy community with a robust understanding of the current landscape of hematopoietic stem cell transplant pharmacy collaborative practice agreements.

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Summary We investigated the incidence of invasive fungal infections (IFIs) and other infectious complications in patients receiving venetoclax and hypomethylating agent therapy for acute myeloid leukaemia (AML). This retrospective, multicentre cohort study included adult patients with AML who received at least one cycle of venetoclax and either azacitidine or decitabine between January 2016 and August 2020. The primary outcome was the incidence of probable or confirmed IFI. Secondary outcomes included antifungal prophylaxis prescribing patterns, incidence of bacterial infections, and incidence of neutropenic fever hospital admissions. Among 235 patients, the incidence of probable or confirmed IFI was 5.1%. IFI incidence did not differ significantly according to age, antifungal prophylaxis use, or disease status. In the subgroup of patients with probable or confirmed IFIs, six (50%) were receiving antifungal prophylaxis at the time of infection. The overall incidence of developing at least one bacterial infection was 33.6% and 127 (54%) patients had at least one hospital admission for febrile neutropenia. This study demonstrated an overall low risk of developing probable or confirmed IFI as well as a notable percentage of documented bacterial infections and hospital admissions due to neutropenic fever.