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.
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.
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.
Introduction: Medical care has recently been moving from wards to outpatient clinics due to a growing number of patients, convenient therapeutic approaches and rising emphasis on quality of life. There is an increased need for intensive monitoring of haemato-oncological patients undergoing long-lasting treatment especially when serious infectious complications are expected. Telemedicine is a great tool to keep an eye on patients spending most of their treatment at home, where reaction time plays an important role in reducing the impact of severe adverse events. Methods: We plan on enrolling 100 haemato-oncological patients undergoing treatment who are at high risk of febrile neutropenia and/or sepsis. In the comfort of their homes, selected patients will measure their body temperature, blood pressure and pulse regularly every morning, plus whenever they feel unwell. Contactless measuring is provided by a digital blood pressure monitor and an infrared thermometer. Both devices communicate via bluetooth with a mobile HUB (cell phone), which then encrypts the information and forwards it to the National Monitoring Center. Physicians have real-time access to the measured values through a web portal using any device with an internet connection. Importantly, values registered outside the individually set-up range are immediately sent by SMS to a designated physician, who can then promptly react. Results: In our pilot project, we enrolled 21 patients (33-80 y; median 60 y) including 9 treated for acute leukemia, 5 for multiple myeloma, 4 for chronic lymphocytic leukemia, 1 for myelodysplastic syndrome, 1 for malignant lymphoma and 1 for aplastic anemia. The median duration of monitoring was 6 months (1-16). One thousand, six hundred and twenty-three critical values of systolic (<90-95 mmHg) and diastolic (<50-60 mmHg, >91 mmHg) blood pressure in 19 patients were registered. High blood pressure in patients with inadequate antihypertensive therapy was the most frequent warning. Forty-four critical values of body temperature (>37.9°C) in 6 patients were registered, two cases with concomitant low blood pressure. After a telephone conversation with a physician, ambulatory care was recommended 12 times. Two cases of febrile neutropenia were detected, with the patients instantly hospitalized without progression into sepsis. Four cases of infectious complications (genital herpes, upper respiratory tract infection) with the need for anti-infective therapy and 6 cases of viral infections with only symptomatic treatment indicated were also addressed. Conclusion: Even in a small cohort of patients we demonstrated that the remote monitoring of body temperature, blood pressure and pulse at home enables the early detection of infections and prompt provision of adequate treatment. An evaluation of the financial savings on medical expenses might also be a useful aspect to revise. Disclosures Hajek: Celgene: Honoraria, Other: Consultant or advisory relationship, Research Funding; AbbVie: Other: Consultant or advisory relationship; Bristol-Myers Squibb: Honoraria, Other: Consultant or advisory relationship, Research Funding; Novartis: Other: Consultant or advisory relationship, Research Funding; PharmaMar: Honoraria, Other: Consultant or advisory relationship; Takeda: Honoraria, Other: Consultant or advisory relationship, Research Funding; Janssen: Honoraria, Other: Consultant or advisory relationship, Research Funding; Amgen: Honoraria, Other: Consultant or advisory relationship, Research Funding.
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