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Background: Glofitamab is a bispecific antibody with promise for treating relapsed/refractory B‐cell lymphoma according to a phase 1/2 clinical trial. This study examined its real‐world effectiveness. Methods: This was an investigator‐initiated, multicenter retrospective study including 34 patients who had relapsed/refractory B‐cell lymphomas after at least three prior lines of therapy and received glofitamab monotherapy in a compassionate use program in Taiwan between January 2021 and October 2022. Results: At a median follow‐up of 15.9 months, 56% of patients responded to glofitamab and 23% achieved complete remission. Response to the previous line of therapy significantly correlated with response to glofitamab (p =.020). Most responses were durable; only five out of the 19 responders had documented disease recurrence at the data cutoff date. The estimated progression‐free survival (PFS) was 3.2 months, and the estimated 1‐year PFS was 33% for the entire cohort. PFS was better for responders than nonresponders (median PFS, 16.9 vs. 1.8 months; 1‐year PFS, 60% vs. 0%). Forty‐three cytokine release syndrome (CRS) events were observed, three of which were grade 3; all were manageable without glofitamab discontinuation. No immune effector cell–associated neurotoxicity was reported. Among seven hepatitis B virus (HBV) carriers (six had antiviral prophylaxis) and 14 patients with remote HBV (four had antiviral prophylaxis), no HBV reactivation was observed. Conclusions: In this real‐world cohort, glofitamab exhibited effectiveness comparable to trial results without excessive CRS or new safety issues. With appropriate prophylaxis, glofitamab‐treated patients with chronic or remote HBV infection are unlikely to experience virus reactivation. [ABSTRACT FROM AUTHOR]

Background: Teclistamab, a B‐cell maturation antigen × CD3 bispecific antibody, demonstrated an overall response rate of 63.0% in 165 heavily pretreated patients with relapsed or refractory multiple myeloma in the phase 1/2 MajesTEC‐1 study. Cytokine release syndrome (CRS), a known manifestation of T‐cell redirection, was observed in 119 of 165 patients (72.1%). Methods: Patients received once‐weekly teclistamab 1.5 mg/kg subcutaneously after two step‐up doses (0.06 and 0.3 mg/kg). CRS was graded according to American Society for Transplantation and Cellular Therapy criteria and managed according to the study protocol, including use of tocilizumab and/or steroids. Results: Most cases of CRS occurred during the step‐up dosing schedule of teclistamab and were grade 1 (50.3% of patients) or grade 2 (21.2% of patients); a single case of grade 3 CRS was reported in a patient with concurrent grade 3 pneumonia. All CRS cases resolved and none led to treatment discontinuation. Overall, 33.3% of patients had >1 CRS event; CRS recurrence was reduced when tocilizumab was administered for the first CRS event compared with when it was not (20.0% vs. 62.2%, respectively). Baseline characteristics such as tumor burden and cytokine levels did not appear to predict CRS incidence or severity. Conclusions: Findings of this study support the need for preemptive planning and prompt management of CRS in patients treated with T‐cell–engaging bispecific antibodies. Intervention with tocilizumab for CRS appears to decrease the likelihood of patients experiencing subsequent CRS events without compromising response to teclistamab. Plain language summary: Cytokine release syndrome (CRS), observed in 72.1% of patients treated with teclistamab in the MajesTEC‐1 study, was mostly grade 1 or 2 and manageable, without requiring treatment discontinuation.Most CRS occurred during the step‐up schedule, requiring vigilance during treatment initiation.Ensure fever is resolved and patients have no signs of infection before initiating the teclistamab step‐up schedule or administering the next teclistamab dose, to avoid exacerbating CRS.Tocilizumab reduced the risk of subsequent CRS in patients receiving it for their first CRS event (20.0% vs. 62.2% in those not receiving it), without affecting response to teclistamab.No baseline characteristics, including tumor burden or cytokine levels, appeared to clearly predict for CRS occurrence or severity. In the MajesTEC‐1 study of the B‐cell maturation antigen × CD3 bispecific antibody teclistamab, cytokine release syndrome (CRS) occurred in 72.1% of heavily pretreated patients with relapsed or refractory multiple myeloma. Most cases of CRS occurred during the step‐up dosing schedule of teclistamab and were grade 1 or 2 and manageable; tocilizumab reduced the incidence of subsequent CRS in patients who received it for their first CRS event (20.0% vs. 62.2% in those not receiving it), without affecting response to teclistamab. [ABSTRACT FROM AUTHOR]

Background: Individuals of advanced age with comorbidities face a higher risk of death from coronavirus disease 2019 (COVID‐19), especially once they are ventilator‐dependent. Respiratory decline in patients with COVID‐19 is precipitated by a lung‐mediated aberrant immune cytokine storm. Low‐dose lung radiation was used to treat pneumonia in the pre‐antibiotic era. Radiation immunomodulatory effects may improve outcomes for select patients with COVID‐19. Methods: A single‐institution trial evaluating the safety and efficacy of single‐fraction, low‐dose whole‐lung radiation for patients with COVID‐19 pneumonia is being performed for the first time. This report describes outcomes of a planned day 7 interim analysis. Eligible patients were hospitalized, had radiographic consolidation, required supplemental oxygen, and were clinically deteriorating. Results: Of 9 patients screened, 5 were treated with whole‐lung radiation on April 24 until April 28 2020, and they were followed for a minimum of 7 days. The median age was 90 years (range, 64‐94 years), and 4 were nursing home residents with multiple comorbidities. Within 24 hours of radiation, 3 patients (60%) were weaned from supplemental oxygen to ambient air, 4 (80%) exhibited radiographic improvement, and the median Glasgow Coma Scale score improved from 10 to 14. A fourth patient (80% overall recovery) was weaned from oxygen at hour 96. The mean time to clinical recovery was 35 hours. There were no acute toxicities. Conclusions: In a pilot trial of 5 oxygen‐dependent elderly patients with COVID‐19 pneumonia, low‐dose whole‐lung radiation led to rapid improvements in clinical status, encephalopathy, and radiographic consolidation without acute toxicity. Low‐dose whole‐lung radiation appears to be safe, shows early promise of efficacy, and warrants further study. Lay Summary: Researchers at Emory University report preliminary safety outcomes for patients treated with low‐dose lung irradiation for coronavirus disease 2019 (COVID‐19) pneumonia.Five residents of nursing or group homes were hospitalized after testing positive for COVID‐19. Each had pneumonia visible on a chest x‐ray, required supplemental oxygen, and experienced a clinical decline in mental status or in work of breathing or a prolonged or escalating supplemental oxygen requirement.A single treatment of low‐dose (1.5‐Gy) radiation to both lungs was delivered over the course of 10 to 15 minutes. There was no acute toxicity attributable to radiation therapy. Within 24 hours, 4 patients had rapidly improved breathing, and they recovered to room air at an average of 1.5 days (range, 3‐96 hours). Three were discharged at a mean time of 12 days, and 1 was preparing for discharge.Blood tests and repeat imaging confirm that low‐dose whole‐lung radiation treatment appears safe for COVID‐19 pneumonia. Further trials are warranted. In 5 elderly, oxygen‐dependent, and clinically declining nursing home residents with coronavirus disease 2019 (COVID‐19), low‐dose whole‐lung radiation has led to rapid clinical recovery and improvement in encephalopathy in an average of 24 to 36 hours, radiographic improvement by day 7, and hospital discharge an average of 12 days later—all without any acute toxicity. Low‐dose whole‐lung radiation appears to be safe, shows early signs of efficacy in COVID‐19, and warrants further study. [ABSTRACT FROM AUTHOR]

In November 2021, the American Society of Clinical Oncology (ASCO) released a new guideline entitled "Management of Immune-Related Adverse Events in Patients Treated With Chimeric Antigen Receptor T-Cell Therapy."1 The guideline, created by a multidisciplinary panel of medical oncology, neurology, hematology, emergency medicine, nursing, trialist, and advocacy experts, was developed through a systematic literature review of evidence published from 2017 to 2021 and an informal consensus process. Thus, it is important to recognize the potential toxicities of this novel therapy not only for treating physicians but also for the nursing staff and other physicians who may come into close contact with patients who have had CAR T-cell therapy. ASCO releases guideline on CAR T-cell therapy: A multidisciplinary team's recommendations help in the recognition, workup, evaluation, and management of the most common chimeric antigen receptor (CAR) T-cell-related toxicities. [Extracted from the article]