Promising Immunotherapeutic Modalities for B-Cell Lymphoproliferative Disorders.

Over the last few years, treatment principles have been changed towards more targeted therapy for many B-cell lymphoma subtypes and in chronic lymphocytic leukemia (CLL). Immunotherapeutic modalities, namely monoclonal antibodies (mAbs), bispecific antibodies (bsAbs), antibody-drug conjugates (ADCs), and chimeric antigen receptor T (CAR-T) cell therapy, commonly use B-cell-associated antigens (CD19, CD20, CD22, and CD79b) as one of their targets. T-cell engagers (TCEs), a subclass of bsAbs, work on a similar mechanism as CAR-T cell therapy without the need of previous T-cell manipulation. Currently, several anti-CD20xCD3 TCEs have demonstrated promising efficacy across different lymphoma subtypes with slightly better outcomes in the indolent subset. Anti-CD19xCD3 TCEs are being developed as well but only blinatumomab has been evaluated in clinical trials yet. The results are not so impressive as those with anti-CD19 CAR-T cell therapy. Antibody-drug conjugates targeting different B-cell antigens (CD30, CD79b, CD19) seem to be effective in combination with mAbs, standard chemoimmunotherapy, or immune checkpoint inhibitors. Further investigation will show whether immunotherapy alone or in combinatory regimens has potential to replace chemotherapeutic agents from the first line treatment.

Osteolytic bone lesions, hypercalcemia and paraprotein, but not a myeloma: case report and review of literature.

In June 2018, 77-year-old man was referred to The Department of Haematooncology, University Hospital Ostrava, for suspicion of multiple myeloma. This was supported by laboratory findings of hypercalcemia, paraprotein IgA κ in serum and by the presence of multiple osteolytic skeletal lesions. Low number of plasma cells in bone marrow sample - cytologically (3.6 %) as well as in flow cytometry (less than 95 % clonal plasma cells out of total bone marrow plasma cells) - pointed at the direction of monoclonal gammopathy of undetermined significance (MGUS). In the course of differential diagnosis of hypercalcemia, elevated level of parathormone had been found which led to the performance of 99mTc-MIBI scintigraphy where parathyroid adenoma was discovered and later histologically verified. The final diagnosis was determined as a coincidence of MGUS and primary hyperparathyroidism. This case report also contains brief differential diagnosis of hypercalcemia and osteolytic skeletal lesions and suggestions for their diagnostic algorithms.

The Benefit of Telemonitoring in the Prevention of Septic Shock in a Patient with Aggressive Non-Hodgkin's Lymphoma.

Telemonitoring is a great tool for vital signs monitoring in patients at high risk of severe life-threatening infections, such as haemato-oncological patients. As it can detect early symptoms of an infection, it allows early reaction and, therefore, can help prevent the progression of the infection into severe sepsis. We present a case report of a 69-year-old patient with aggressive non-Hodgkin lymphoma undergoing intensive immunochemotherapy. The treatment was complicated by two episodes of Gram-negative bacterial (G-) infection. During the first episode, the patient was admitted to the hospital only after developing septic shock with multiorgan dysfunction syndrome, which required vasopressor support and multiple broad-spectrum antibiotics and other antimicrobial therapy. Following this episode, the patient was enrolled in our telemonitoring project focusing on early detection of infections in high-risk haemato-oncological patients. The patient later developed another infection with G- bacteremia; however, thanks to the telemonitoring, he was admitted to the hospital within a few hours after developing (and detecting) fever. The therapy was initiated immediately, and the infection was successfully managed with first-choice antibiotics without any further complications. This case illustrates the importance of early detection of infection in high-risk patients, as well as the benefits of telemonitoring. Moreover, avoidance of septic shock and the consequent need for intensive care can significantly reduce healthcare costs.

An economic evaluation of the effectiveness of telemedicine in hematooncology.

The article examines the effectiveness of remote monitoring and the evaluation of facts about patients with hematologic malignancies using telemedicine based on SMART technologies. The project was carried out in the Department of Haematooncology of the University Hospital Ostrava. Its objective was to test the efficacy of telemedicine in the treatment of patients with blood cancer. The cost-benefit analysis method was used to evaluate effectiveness, which also confirmed the feasibility of using this method to evaluate the costs and benefits of implementing specific medical projects. The conducted analysis demonstrated the effectiveness of using telemedicine procedures in the treatment of these patients, both in terms of quantifiable and non-quantifiable impacts on the Czech Republic's health system. This was mainly due to a large shortening of the length of the hospitalisation period for patients with problems whose deterioration was discovered by remote monitoring and their treatment could begin promptly. The shortening of the hospitalization period was achieved by around 40%. As a result, the complexity of treatment has been greatly reduced, benefiting both the hospital and, most importantly, the patient. With this prevention, the patient's chances of dying are reduced, as he or she is less likely to develop severe septic diseases. The total average financial savings of the Czech Republic's entire health care system for a patient who does not become septic due to a delayed response to deteriorating health only in hospitalisation, treatment, and medications is approximately USD 2,800.

Management of Treatment-Related Infectious Complications in High-Risk Hemato-Oncological Patients via Telemedicine.

Background: Infectious complications, especially febrile neutropenia, in hemato-oncological patients are associated with considerable morbidity, mortality and expenses. Remote monitoring of physiological functions and thus early detection of adverse events via telemedicine could improve the safety of these high-risk patients and save financial resources by shortening the time-to-antibiotics. Methods: Patients undergoing active cancer treatment in high risk of acquiring severe infection are selected and enrolled in this project. Each patient receives a digital blood pressure monitor, an infrared thermometer and a mobile hub (cell phone). In the comfort of their homes, patients measure their blood pressure/pulse and body temperature regularly or whenever they feel unwell. The obtained data are encrypted and forwarded via the mobile hub to the password-protected portal. The values registered outside the set-up range trigger the alarms, which are immediately sent to the designated physician who can check the portal in real-time from any device with an Internet connection, contact the patient, if need be, and initiate the anti-infective therapy almost instantly after the first symptoms occur. Results: Fifty hemato-oncological patients were recruited between March 1, 2018 and August 1, 2020. Two hundred ninety-seven alarms of body temperature were registered and checked by the physician and patients were contacted in 18.5% of the cases (55/297). Among these 55 events, 13 required medical assistance, which makes it approximately one-quarter of all conducted telephone interventions (23.4%) and neither septic shock nor death due to treatment-related toxicity occurred. Conclusion: Telemedicine seems like a useful tool to improve the safety of high risk hemato-oncological patients when treatment-related infectious complications are concerned.

Toxicity of Immune-Checkpoint Inhibitors in Hematological Malignancies.

Immune checkpoint inhibitors (ICIs), especially those targeting the programmed-death 1 (PD-1) receptor and its ligands, have become indispensable agents in solid tumor anti-cancer therapy. Concerning hematological malignancies, only nivolumab and pembrolizumab have been approved for the treatment of relapsed and refractory classical Hodgkin lymphoma and primary mediastinal large B cell lymphoma to date. Nevertheless, clinical research in this field is very active. The mechanism of action of ICIs is based on unblocking the hindered immune system to recognize and eliminate cancer cells, but that also has its costs in the form of ICI-specific immune related adverse events (irAEs), which can affect any organ system and can even be lethal. In this article, we have reviewed all prospective blood cancer clinical trials investigating ICIs (both monotherapy and combination therapy) with available toxicity data with the purpose of determining the incidence of irAEs in this specific setting and to offer a brief insight into their management, as the use of immune checkpoint blockade is not so frequent in hemato-oncology.

Identifying and treating candidates for checkpoint inhibitor therapies in multiple myeloma and lymphoma.

Introduction: One of the hallmarks of cancerogenesis is the ability of tumor cells to evade the immune system. They can achieve it by abusing inhibitory immune checkpoint pathways, which, under normal circumstances, maintain peripheral tolerance during infection. Immune checkpoint inhibitors, especially anti-PD-1/PD-L1 monoclonal antibodies, currently represent a widely discussed treatment option not only in solid oncology, but in hematology-oncology as well.Areas covered: The manuscript is focused on clinical research concerning PD-1/PD-L1 blockade in lymphoma and multiple myeloma in order to identify the patients who would profit the most from this treatment modality. The authors reviewed articles on the topic on PubMed and relevant clinical trials on clinicaltrials.gov before October 2019.Expert opinion: So far, nivolumab and pembrolizumab have been approved for treating patients with relapsed/refractory classical Hodgkin lymphoma and primary mediastinal B cell lymphoma. Nevertheless, monotherapy alone is not curative and a combinational approach is needed. Modern treatment strategies and combinations are comprehensively summarized in this manuscript. There is no approved immune checkpoint inhibitor for the multiple myeloma indication. Although the combination of PD-1/PD-L1 inhibitors with immunomodulatory agents initially seemed promising, unexpected immune related toxicities have stopped any further development. Novel strategies and more potent combinations in myeloma and lymphoma are further discussed in the manuscript.