Time and personnel costs associated with adverse event (AE) management among patients with chronic lymphocytic leukemia (CLL).

OBJECTIVES: Novel therapies improve clinical outcomes in chronic lymphocytic leukemia (CLL), although adverse event (AE) profiles differ. This study evaluated time and personnel costs of AE management among healthcare professionals (HCPs) treating patients with CLL with novel therapies. METHODS: A non-interventional prospective survey was conducted over 2 months. Eligible HCPs reported the time per day spent performing AE management activities for CLL patients treated with acalabrutinib, ibrutinib, or venetoclax. Mean time and personnel costs (USD) per activity were summarized and used to estimate the total annual costs of AE management for an average-sized oncology practice. RESULTS: For an average-sized practice (28 HCPs with an average of 56 CLL patients), the mean annual personnel cost of AE management for CLL patients on novel agents was estimated at $115,733. The personnel cost associated with acalabrutinib ($20,912) was less than half that of ibrutinib ($53,801) and venetoclax ($41,884), potentially due to fewer severe AEs and less time spent by oncologists managing AEs compared to other HCP types. CONCLUSION: The substantial burden of AE management for patients with CLL may vary by treatment used. Acalabrutinib was associated with lower annual costs of AE management at an oncology practice level compared to ibrutinib and venetoclax.

Post-transplant cyclophosphamide and early mixed donor Chimerism in myeloid malignancies; a single-center experience.

BACKGROUND: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the only curative option for high-risk myeloid malignancies. Post-transplant cyclophosphamide (PT-Cy) has proven to be effective for graft versus host disease (GVHD) prophylaxis. Given that graft-versus-tumor (GVT) effect plays a major role in reducing the risk of disease relapse, the application of PT-Cy must balance the risk of relapse. Mixed chimerism (MC) refers to a state of concurrent presence of recipient and donor cells post allo-HSCT which may precede relapse disease. OBJECTIVE: We investigated the impact of PT-Cy on early MC (EMC) and disease relapse in patients with a myeloid malignancy post allo-HSCT. STUDY DESIGN: This retrospective single-center study included patients that underwent allo-HSCT between 2015 and 2021. Patient and disease characteristics were collected from the electronic health records. EMC was defined as <95% donor cells at day 90-120 post allo-HSCT. RESULTS: A total of 144 patient that received an allo-HSCT were included in the study. One hundred and eight (75%) patients received PT-Cy as part of the GVHD prophylaxis regimen. The majority underwent allo-HSCT for acute myeloid leukemia (62%) or myelodysplastic syndrome (31%). Sixty-five percent received allo-HSCT from a matched unrelated donor transplant and 65% received a myeloablative conditioning regimen. A lower rate of chronic GVHD (p = 0.03) and a higher rate of EMC (p = 0.04) were observed in patients that received PT-Cy. PT-Cy was not associated with overall survival (OS) and relapse-free survival (RFS). Multivariable analysis identified measurable residual disease status (p = 0.003), hematopoietic cell transplantation-specific comorbidity index (p = 0.012) and chronic GVHD (p = 0.006) as independent prognostic variables for OS. AML-adverse risk (p = 0.004) and EMC (p = 0.018) were independently prognostic for RFS. While EMC overall was not significantly associated with higher risk of relapse, EMC was associated with shorter RFS within adverse-risk AML patients. CONCLUSION: Our study shows that PT-Cy was associated with an increased risk of EMC. The predictive value of EMC for relapse remains unclear and may depend on the underlying disease, which should be validated in a larger cohort.

Combined immune checkpoint blockade and radiotherapy induces durable remission in relapsed natural killer/T-cell lymphoma: a case report and review of the literature.

BACKGROUND: Extranodal natural killer/T-cell lymphoma is a rare, aggressive non-Hodgkin lymphoma that is treated upfront mostly with L-asparaginase containing regimens. Relapsed extranodal natural killer/T-cell lymphoma is associated with a poor prognosis, and there is no established standard of care. CASE PRESENTATION: We report the case of a 72 year-old white male with a distant extranasal relapse of extranodal natural killer/T-cell lymphoma that has been managed successfully with a combination of radiation and immune checkpoint blockade with pembrolizumab. Pseudoprogression with new skin and bone lesions on positron emission tomography imaging was encountered during this Caucasian patient's immunotherapy and was successfully managed with supportive care and continuation of immune checkpoint blockade. CONCLUSIONS: The patient has been in complete clinical, radiologic, and molecular remission for close to 3 years and has not had any immune-related adverse effects. Pseudoprogression is a clinical challenge that can be encountered while patients are treated with immunotherapy, and astute clinical acumen is needed for accurate management. We believe this is the longest duration of response to immune checkpoint blockade in relapsed extranodal natural killer/T-cell lymphoma reported to date in literature. There is a strong biologic rationale in combining radiation with immunotherapy. The optimal timing, dose, and duration of radiation combined with immunotherapy in extranodal natural killer/T-cell lymphoma need to be prospectively evaluated.

Evaluation of SARS-CoV-2 Serological Testing in Patients with Multiple Myeloma and Other Hematologic Malignancies on Monoclonal Antibody Therapies.

BACKGROUND: Patients with hematological malignancies (HM), including multiple myeloma (MM), frequently suffer from immune deficiency-associated infectious complications because of both the disease and the treatment. Alarming results from China and the UK confirm the vulnerability of HM patients to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection-driven coronavirus disease 2019 (COVID-19). Given that the immunoassay interference from the endogenous monoclonal immunoglobulin (M paraprotein) and treatment antibodies continually challenges the MM management, it is critical to evaluate the SARS-CoV-2 serology tests for suspected interference/cross-reactivity. METHODS: We compared the degree of interference in three SARS-CoV-2 serology assay platforms in HM patients with and without COVID-19 and on various therapeutic monoclonal antibody (t-mAb) treatments. Further, we confirmed the cross-reactivity in pooled samples from normal and COVID-19 + samples spiked with respective antibodies in vitro. RESULTS: None of the 93 HM patient samples with or without t-MAbs showed cross-reactivity on any of the three serology platforms tested. CONCLUSIONS: The tested three serologic assays for SARS-CoV-2 are specific and do not have cross-reactivity with M-components or t-MAbs indicating that they can be used safely in oncology practice and in research exploring the immunologic response to COVID-19 in patients with HM.

Complete Depletion of Daratumumab Interference in Serum Samples from Plasma Cell Myeloma Patients Improves the Detection of Endogenous M-Proteins in a Preliminary Study.

BACKGROUND: Therapeutic humanized IgG1 kappa monoclonal antibody (t-mAb), daratumumab (DARA) is a Food and Drug Administration approved drug for the treatment of relapsed/refractory plasma cell myeloma (PCM). DARA appears on serum protein electrophoresis (SPEP) and on serum immunofixation (sIFE) as an IgG kappa monoclonal immunoglobulin protein (M-protein), complicating the assessment of the patients' response to therapy. A more ominous threat to patient safety can occur with the misinterpretation of the presence of a small t-mAb spike as being the residual product of the patient's neoplastic clone, presented either as oligoclonality or new clonality, which could result in incorrect interpretation of failure to achieve remission. METHODS: In this report, we describe a novel and cost-effective technique based on biotinylated recombinant CD38 and streptavidin-coated magnetic beads to capture and remove residual DARA present in PCM patient serum samples. The treated samples are then run like regular samples on SPEP and sIFE. We validated this simple technique in DARA-spiked PCM samples and patient samples on DARA treatment. RESULTS: Our simple capture technique completely extracted DARA in all of the tested serum specimens and allowed the assessment of residual M-protein without DARA interference. The results were reproducible and highly specific for DARA, and did not have any impact on endogenous M-protein migration and quantification by SPEP and sIFE. The cost of this technique is much lower and it can be performed in-house with a very short turnaround time compared to the currently available alternative methods. There is a great need for such reflex technologies to avoid interpretation errors. CONCLUSIONS: This method is an effective way to eliminate DARA interference in SPEP and sIFE, and can be easily implemented in any clinical laboratory without any patent restriction. This simple technique can be adopted for other t-mAbs using their respective ligands and will help to reduce additional doses of toxic treatment and further testing in patients on t-mAbs with a false positive M-protein spike.

Update on the pharmacological prevention of skeletal-related events in cancer patients.

Metastases to the bone are a frequent complication of advanced cancer. Bone metastases have been linked to skeletal-related events, which is the composite endpoint used in clinical trials evaluating therapy to minimize these complications. This article discusses bisphosphonates, which are the historical standard for the prevention of skeletal-related events in patients with metastases from solid tumors and multiple myeloma, and denosumab, which is the first Food and Drug Administration-approved receptor activator of nuclear factor kappa-ß ligand (RANKL) inhibitor.