Background : The safety and efficacy of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) emergency-use authorized (EUA) vaccines has been confirmed in general population. However, there is no data on its safety/tolerability or efficacy in recipients of allogeneic hematopoietic stem cell transplant (HCT). Objectives : We performed this study to identify the incidence of adverse events following SARS-CoV2 EUA vaccines and the incidence of new onset GVHD or worsening of existing GVHD after EUA vaccine administration and the incidence SAR-CoV2 positivity in vaccinated HCT patients. Study Design : We retrospectively reviewed 113 HCT patients who received at least one dose of EUA vaccine to describe the safety/tolerability, any impact on graft-versus-host disease (GVHD), and incidence of SARS-CoV2 PCR positivity after vaccination. Patients received either Pfizer (BNT162b2) or Moderna (mRNA-1273) vaccines. Patients were included if they were 18 years or older and received at least one dose of vaccine in the post HCT setting. Results : Most patients presented with myalgias/arthralgias (first dose 7.7%, second dose 14.6%), fatigue (first dose 15.4%, second dose 29.2%), and injection site pain (first dose 40.4%, second dose 43.8%). Other side effects experienced by patients included: nausea, vomiting, diarrhea, headache, injection-site rash and swelling. Liver function abnormalities occurred in 18.6% of patients. The incidence of neutropenia, thrombocytopenia, and lymphopenia occurred at 13.3%, 11.5%, and 8.8% respectively. Forty percent of patients who had active chronic GVHD at the time of vaccination where worsening chronic GVHD occurred in 3.5% of patients. New chronic GVHD developed in 9.7% of patients after vaccination. Conclusion : In conclusion, the SARS-CoV2 EUA vaccines were well-tolerated in allogeneic HCT recipients.

No abstract

Objective: To summarize and review the clinical data of Food and Drug Administration (FDA)-approved biosimilars for use in treatment of cancer and the current challenges health care institutions face when implementing a newly approved biosimilar. Data Sources: A literature search of the following databases was performed between January 1, 2012, and December 31, 2019: PubMed, Google, and ClinicalTrials.gov. Search terms included the words biosimilar, bevacizumab, rituximab, and/or trastuzumab. Study Selection and Data Extraction: Only primary literature on biosimilars with an ongoing or completed phase 3 trial and/or FDA approval were included in the final analysis. Primary literature consisted of peer-reviewed publications, published abstracts, and any results posted on the ClinicalTrials.gov database. Data Synthesis: Clinical trials of FDA-approved biosimilars for bevacizumab, rituximab, and trastuzumab showed no significant differences with respect to efficacy, safety, and pharmacokinetics when compared with their reference products. Relevance to Patient Care and Clinical Practice: The anticipated growth of biologics in oncology and the recent introduction of biosimilars over the past few years have placed a lot of emphasis on biosimilars as a significant source of cost savings for the health care system. Our article compiles and analyzes existing data on biosimilar efficacy, safety, and financial impact. Conclusions: The major concerns of biosimilars revolve around their long-term efficacy and safety. Even with many questions to be answered, biosimilars have the potential for significant cost savings in the US health care system.

Purpose: Primary objective is to evaluate safety of isavuconazonium sulfate (ISA) in pediatrics below 18 years old. Exploratory endpoint includes mortality due to probable and proven invasive fungal infection (IFI) and overall morality in this population. Patients and Methods: Retrospective review of patients below 18 years receiving ISA for ≥7 days for possible, probable, or proven IFI or prophylaxis between June 2015 and March 2018. Descriptive analysis performed to calculate median, frequency, and percentages. Results: Safety analysis included 18 patients and a subgroup of 11/18 patients were assessed for efficacy. Median age 12.5 years (4 to 17 y), median weight 50.25 kg (19 to 118 kg), 50% male, 77% acute leukemias, 94% hematopoietic cell transplant recipients, 50% matched unrelated donors and 78% in remission. Elevated alanine aminotransferase 3 times baseline within 30 days of ISA occurred in 22% (4/18). No patients had elevated bilirubin or increase in serum creatinine. All-cause mortality at 90 days was 22% (4/18) and 27% (3/11) in patients with probable or proven IFI. Clinical response rates: 14-day: 45% (5/11) partial, 27% (3/11) stable; 30-day: 45% (5/11) partial, 36% (4/11) stable; 90-day: 54% (6/11) had either partial (n=3) or complete (n=3) response to ISA. Conclusions: ISA is safe in pediatric patients for the treatment of IFI. Prospective, randomized controlled trials are warranted to determine efficacy and safety of ISA in pediatric patients with hematologic malignancies and hematopoietic cell transplant.

No abstract

A 26-year-old male with a history of pre-B cell acute lymphoblastic leukemia and seizures presented with second relapse of acute lymphoblastic leukemia and central nervous system involvement, 19 years after the initial diagnosis. Over the next two months, the patient received six doses of triple intrathecal chemotherapy (cytarabine, methotrexate, and hydrocortisone), three concurrently with continuous blinatumomab in the second month. Approximately 12 days after blinatumomab initiation, he developed central nervous system toxicity manifesting as speech impairment, altered mental status, incontinence, and diffuse weakness. Blinatumomab was discontinued, and he was started on dexamethasone. Within the next couple of months, his neurologic status recovered, and he was able to perform all of his baseline activities without limitation. Unfortunately, the patient eventually expired after further relapse approximately one year later. To our knowledge, this is the first published case report of severe neurotoxicity in a patient who was given blinatumomab concurrently with intrathecal chemotherapy.

This study reports the incidence of chronic graft versus host disease (GvHD) in allogeneic hematopoietic stem cell transplant (alloHCT) recipients who received SARS-CoV2 vaccination. The overall rates of new and worsening chronic GvHD combined were 14%, with median time from vaccination to GVHD being approximately three to four weeks. A majority of the cases were of mild to moderate severity and primarily localized to either the skin, mouth, or joints. Prior chronic GVHD and recent transplant were associated with higher GVHD rates following COVID-19 vaccination. More prospective studies are needed to provide a definitive mechanism for the impact of SARS-CoV2 vaccination on alloHCT patients.

No abstract