Shejal Patel

BACKGROUND: Many older adults with B-cell precursor acute lymphoblastic leukemia (BCP-ALL) have a relapse despite having a measurable residual disease (MRD)-negative complete remission with combination chemotherapy. The addition of blinatumomab, a bispecific T-cell engager molecule that is approved for the treatment of relapsed, refractory, and MRD-positive BCP-ALL, may have efficacy in patients with MRD-negative remission. METHODS: -negative BCP-ALL (with :: indicating fusion) who had MRD-negative remission (defined as <0.01% leukemic cells in bone marrow as assessed on flow cytometry) after induction and intensification chemotherapy to receive four cycles of blinatumomab in addition to four cycles of consolidation chemotherapy or to receive four cycles of consolidation chemotherapy alone. The primary end point was overall survival, and relapse-free survival was a secondary end point. RESULTS: The data and safety monitoring committee reviewed the results from the third efficacy interim analysis and recommended that they be reported. Complete remission with or without full count recovery was observed in 395 of 488 enrolled patients (81%). Of the 224 patients with MRD-negative status, 112 were assigned to each group. The characteristics of the patients were balanced between the groups. At a median follow-up of 43 months, an advantage was observed in the blinatumomab group as compared with the chemotherapy-only group with regard to overall survival (at 3 years: 85% vs. 68%; hazard ratio for death, 0.41; 95% confidence interval [CI], 0.23 to 0.73; P = 0.002), and the 3-year relapse-free survival was 80% with blinatumomab and 64% with chemotherapy alone (hazard ratio for relapse or death, 0.53; 95% CI, 0.32 to 0.87). A higher incidence of neuropsychiatric events was reported in the blinatumomab group than in the chemotherapy-only group. CONCLUSIONS: The addition of blinatumomab to consolidation chemotherapy in adult patients in MRD-negative remission from BCP-ALL significantly improved overall survival. (Funded by the National Institutes of Health and others; E1910 ClinicalTrials.gov number, NCT02003222.).

INTRODUCTION: Up until 2010, the recommended duration of empiric broad-spectrum antibiotics for febrile neutropenia was until absolute neutrophil count (ANC) recovery. An updated guideline on the use of antimicrobial agents in neutropenic patients with cancer indicates that patients who have completed an appropriate treatment course of broad-spectrum antibiotics, with resolution of signs and symptoms of infection but persistent neutropenia, can be de-escalated to oral fluoroquinolone prophylaxis until ANC recovery. METHODS: The primary objective of this retrospective investigation was to evaluate the safety and efficacy of de-escalating broad-spectrum antibiotics in patients remaining neutropenic after at least 14 days of empiric broadspectrum antibiotics for febrile neutropenia compared to patients continuing broad-spectrum antibiotics until ANC recovery. RESULTS: There were 16 patients (61.5%) in the comparator group who met the primary endpoint of remaining afebrile and without escalation of antibiotics for at least 72 hours after 14 days of broad-spectrum antibiotics and 21 patients (80.7%) in the de-escalation group who met the primary endpoint of remaining afebrile and without reinitiation of broad-spectrum antibiotics for at least 72 hours after de-escalation to levofloxacin therapy (p = 0.11). Mean total duration of broad-spectrum antibiotic therapy was 23.5 ± 1.5 days in the comparator group versus 22.2 ± 1.43 days in the de-escalation group (p = 0.39). CONCLUSIONS: Results of this investigation indicate that broad-spectrum antibiotics can be safely de-escalated to levofloxacin prophylaxis prior to ANC recovery in select patients. This practice may decrease the duration of broad-spectrum antibiotic exposure and associated complications.

Background: Patients (pts) with newly diagnosed acute lymphoblastic leukemia (ALL) often relapse even with achieving complete remission (CR) and minimal residual disease (MRD) negative (MRD-) status after chemotherapy (chemo). Blinatumomab (blin) is a bi-specific T cell engager molecule approved for relapsed/refractory ALL pts and pts MRD positive (MRD+) (>0.1%) in 1st or 2nd CR. E1910 was a phase III trial randomizing pts age 30-70 yrs to chemo +/-blin to test whether blin improves outcomes in BCR:ABL-negative B-ALL. The study showed that in pts who were MRD- after induction, there was a significant improvement in overall survival (OS) in favor of the blin arm. These subgroup analyses describe outcomes in pts based on age (< or > 55 yr) and depth of MRD (undetectable vs between undetectable-0.01%). Aims: Primary objective compared OS in MRD- pts who received chemo +/- blin. Subgroup analyses look at outcomes based on age <55 or >=55 yrs, which was a pre-specified stratification factor. Additional subgroup analyses look at depth of MRD below 0.01%, which was not a pre-specified stratification factor. Methods: Pts received 2.5 mo of combination chemo using a BFM-like regimen adapted from the E2993/UKALLXII clinical trial with extended remission induction, addition of pegaspargase for pts <55 yr of age and addition of rituximab for CD20+ pts. Details regarding remission induction (step 1), high dose methotrexate with pegaspargase for CNS prophylaxis (step 2), blin randomization (step 3), and maintenance (step 4) or hematopoietic cell transplant (HCT) were presented previously at ASH 2022. MRD status was determined centrally by 6-color flow cytometry with level of sensitivity of 0.01%. MRD- was defined as <0.01%. With a minimum of 190 MRD- pts, the study had an 80% power to detect a 45% reduction in hazard rate in the blin arm relative to the control chemo arm, using one-sided log rank test at significance level of 0.025 and assuming 2 yrs of follow-up. Estimates of OS were calculated using the Kaplan-Meier method. Comparison of OS between treatment arms was conducted using age, CD20 status, rituximab use, and whether pts were intended to receive HCT or not as stratification factors. Results: 772 pts were screened and 488 were enrolled. Median age was 51 yr. 224 MRD- pts were randomized, 112 pts to each arm. 22 pts in each arm proceeded to allogeneic HCT. The CR/CRi rate after induction was 81%. Among MRD- pts, OS significantly favored the blin arm (median OS: not reached vs. 71.4 mo; Hazard ratio (HR) 0.42, 95% CI: 0.24 - 0.75; two-sided p=0.003). The RFS in MRD- pts (n=224) favored the blin arm (median RFS: not reached vs. 71.4 mo; HR 0.46, 95% CI:.027-0.78; p=0.004). In MRD+ pts (N=62), the OS for blin vs control arm was (median OS: not reached vs 22.4 months; HR 0.39, 95% CI: 0.14-1.10; p=0.066). In MRD- pts < 55 yr (n=132), OS favored the blin arm (median OS not reached vs not reached; HR 0.18, 95% CI: 0.06-0.52; p <0.001). In MRD- pts >55 yr (n=92), the OS for blin vs control arm was (median OS not reached vs. 71.4 mo; HR 0.77, 95% CI: 0.37-1.58; p=0.47). In pts with undetectable MRD (n=187) at randomization, OS favored the blin arm (median OS not reached vs. not reached; HR 0.51, 95% CI: 0.27-0.97; p=0.038). In pts with MRD between undetectable and 0.01% (n=37), the OS for blin vs control arm was (median OS not reached vs. 38.0 mo; HR 0.35, 95% CI 0.06-1.94; p=0.16). Summary/Conclusion: Adding blin to chemo improves OS and RFS in pts MRD- at randomization. The effect of blin was particularly evident in pts < 55 yr and in patients with undetectable MRD. Keywords: B cell acute lymphoblastic leukemia, Acute lymphoblastic leukemia, Immunotherapy

OBJECTIVE: Donation after cardiac death (DCD) or donation of organs after removal of life support is an accepted means of organ retrieval that usually occurs in the setting of sudden illness but has not been described in people with progressive neurologic illness. We report DCD in two people with progressive amyotrophic lateral sclerosis (ALS). METHODS: Case series at an academic medical center of two men with progressive ALS who underwent withdrawal of artificial life support, rapid cardiac death, and subsequent organ donation. The primary outcome was donation of organs in concordance with patient and family wishes. RESULTS: Both patients underwent peaceful withdrawal of life support in the presence of family, and multiple organs were donated. CONCLUSIONS: Patients may legally and ethically refuse life-sustaining care. These patients considered their lives to be more burdensome than beneficial near the end of their lives, both carefully planned the time and circumstance of their deaths, and both fulfilled a long-standing desire to donate their organs. This study describes a potential opportunity for patients with progressive neurologic illness.

Palliative care provides open and honest communication, medically appropriate goal setting, and meticulous attention to symptom assessment and control. The Physicians Orders for Life Sustaining Treatment (POLST) is a growing movement to allow health care providers to indicate, with their patients, what they want done in specific situations, such as feeding tubes, mechanical ventilation, or transfer to an intensive care unit. We have developed an internal signout tool used by palliative medicine fellows in our institution to specify similar interventions-or not-with seriously ill palliative care patients, the Providers Signout for Scope of Treatment (PSOST). We have found that this situation-specific tool enables smooth transitions of care on nights and weekends, especially when the patient is near death, and may help prevent both overescalation of care and underuse of life saving treatments such as resuscitation. The PSOST differs from other signout tools in that it gives clear direction regarding the patient's medical goals and desire for escalation of care, or not. We present it here for open access and use anywhere. This tool has also assisted in building team communication with the nursing shifts, especially nights and weekends, as all team members are able to deliver a consistent message, while meeting the goals of care for patients and families. We believe this tool could be useful with a broader patient population, outside of Palliative Medicine, to provide clearer direction for hospitalized or nursing home patients whose care is often directed by multiple providers. It could also be used as a template for signouts on other inpatient services, as care goals are important for all patients.