Safety and efficacy of eltrombopag in patients with post-CAR T cytopenias.

BACKGROUND: While chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment outcomes of relapsed/refractory hematological malignancies, this therapy is associated with post-treatment cytopenias, which can pose a challenge to its safe administration. This study describes the management of post-CAR T cytopenias using the thrombopoietin mimetic eltrombopag. METHODS: This retrospective analysis included adult patients with lymphoma or myeloma who received CAR T-cell therapy at two academic medical centers. Eltrombopag was initiated for patients who had persistent high-grade leukopenia and/or thrombocytopenia beyond 21 days post-CAR T infusion. Risk factors and outcomes were assessed and compared for patients who did or did not receive eltrombopag. RESULTS: Among the 185 patients analyzed, a majority (88%) experienced thrombocytopenia or leukopenia at day +30 post-CAR T infusion. A total of 42 patients met the criteria for eltrombopag treatment and initiated therapy. Patients who received eltrombopag were more likely to have pre-existing cytopenias at lymphodepletion, receive bridging therapy, experience an infection, or require intensive care. Recovery from cytopenias occurred within 180 days for a majority (94%) of patients. CONCLUSIONS: The use of eltrombopag for post-CAR T leukopenia and thrombocytopenia was considered safe without any significant toxicities. The use of eltrombopag for post-CAR T cytopenias might be effective in a high-risk patient population but requires further study.

Exploring the High-Grade and Refractory Neurotoxicity of Teclistamab: An Underreported Entity.

T-cell re-directing bispecific antibodies targeting B-cell maturation antigens have recently entered real-world use in relapsed/refractory multiple myeloma. While no head-to-head comparison has been done, they have generally been observed to have lower-grade toxicities compared with their chimeric antigen receptor T-cell (CAR-T) counterparts. However, in our real-world, single-institution experience, we have encountered two patients receiving teclistamab who experienced high-grade and refractory immune effector cell-associated neurotoxicity syndrome (ICANS) that did not respond to traditional toxicity mitigation strategies of high-dose corticosteroids or other immunosuppressive therapies. As we increase our use of these novel and vital agents, caution must be warranted.

Evaluation of the Durability of the Immune Humoral Response to COVID-19 Vaccines in Patients With Cancer Undergoing Treatment or Who Received a Stem Cell Transplant.

Importance: The durability of the antibody response to COVID-19 vaccines in patients with cancer undergoing treatment or who received a stem cell transplant is unknown and may be associated with infection outcomes. Objective: To evaluate anti-SARS-CoV-2 spike protein receptor binding domain (anti-RBD) and neutralizing antibody (nAb) responses to COVID-19 vaccines longitudinally over 6 months in patients with cancer undergoing treatment or who received a stem cell transplant (SCT). Design, Setting, and Participants: In this prospective, observational, longitudinal cross-sectional study of 453 patients with cancer undergoing treatment or who received an SCT at the University of Kansas Cancer Center in Kansas City, blood samples were obtained before 433 patients received a messenger RNA (mRNA) vaccine (BNT162b2 or mRNA-1273), after the first dose of the mRNA vaccine, and 1 month, 3 months, and 6 months after the second dose. Blood samples were also obtained 2, 4, and 7 months after 17 patients received the JNJ-78436735 vaccine. For patients receiving a third dose of an mRNA vaccine, blood samples were obtained 30 days after the third dose. Interventions: Blood samples and BNT162b2, mRNA-1273, or JNJ-78436735 vaccines. Main Outcomes and Measures: Geometric mean titers (GMTs) of the anti-RBD; the ratio of GMTs for analysis of demographic, disease, and treatment variables; the percentage of neutralization of anti-RBD antibodies; and the correlation between anti-RBD and nAb responses to the COVID-19 vaccines. Results: This study enrolled 453 patients (mean [SD] age, 60.4 [13,1] years; 253 [56%] were female). Of 450 patients, 273 (61%) received the BNT162b2 vaccine (Pfizer), 160 (36%) received the mRNA-1273 vaccine (Moderna), and 17 (4%) received the JNJ-7846735 vaccine (Johnson & Johnson). The GMTs of the anti-RBD for all patients were 1.70 (95% CI, 1.04-2.85) before vaccination, 18.65 (95% CI, 10.19-34.11) after the first dose, 470.38 (95% CI, 322.07-686.99) at 1 month after the second dose, 425.80 (95% CI, 322.24-562.64) at 3 months after the second dose, 447.23 (95% CI, 258.53-773.66) at 6 months after the second dose, and 9224.85 (95% CI, 2423.92-35107.55) after the third dose. The rate of threshold neutralization (≥30%) was observed in 203 of 252 patients (80%) 1 month after the second dose and in 135 of 166 patients (81%) 3 months after the second dose. Anti-RBD and nAb were highly correlated (Spearman correlation coefficient, 0.93 [0.92-0.94]; P < .001). Three months after the second dose, anti-RBD titers were lower in male vs female patients (ratio of GMTs, 0.52 [95% CI, 0.34-0.81]), patients older than 65 years vs patients 50 years or younger (ratio of GMTs, 0.38 [95% CI, 0.25-0.57]), and patients with hematologic malignant tumors vs solid tumors (ratio of GMTs, 0.40 [95% CI, 0.20-0.81]). Conclusions and Relevance: In this cross-sectional study, after 2 doses of an mRNA vaccine, anti-RBD titers peaked at 1 month and remained stable over the next 6 months. Patients older than 65 years of age, male patients, and patients with a hematologic malignant tumor had low antibody titers. Compared with the primary vaccine course, a 20-fold increase in titers from a third dose suggests a brisk B-cell anamnestic response in patients with cancer.

Development of a standardized approach for managing opioids in adults with chronic noncancer pain.

PURPOSE: The implementation of a chronic pain protocol (CPP) and its effects on the management of long-term opioid therapy are described. SUMMARY: The CPP used at a federally qualified health center and primary care clinic was updated in 2015 and included a prescribing ceiling in morphine equivalent dose (MED) per day and standardized the prescribing of chronic opioids. Intermittent urine drug screening performed at least once annually was added as a requirement of the pain management contract between the provider and the patient. An electronic report was developed to identify patients who were receiving long-term opioid therapy at the clinic. The clinical pharmacists identified patients from the report whose long-term opioid doses were over the clinic-recommended MED threshold, needed a pain contract, or were due for a urine drug screen. The number of patients for whom long-term opioids were prescribed decreased for all clinicians, including an 88% reduction by nurse practitioners. Over 12 months, 97 fewer patients with chronic pain were treated with a long-term opioid at the clinic. The number of patients with pain contracts increased by 22.9% (p < 0.001), and the number of patients who had a urine drug screen over a 12-month period increased by 18.3% (p = 0.0016). CONCLUSION: The implementation of a CPP and the development of electronic reports to track provider adherence to the protocol led to a reduction in the number of chronic pain patients receiving long-term opioid therapy. The number of patients with pain contracts increased.

Utilization of influenza and streptococcal pharyngitis point-of-care testing in the community pharmacy practice setting.

BACKGROUND: One way to reduce the complications and costs of influenza like illness and pharyngitis is to improve access to testing and treatment in early stages of infection. Pharmacy-based screening and treatment of group A streptococcus (GAS) infection and influenza has the potential to improve patient care and population health. OBJECTIVE: To improve patient care and population health, the objective of this retrospective study was to assess if a previously validated service model could be implemented by pharmacy chains without mandated standardization. METHODS: Researchers utilized a certificate program to provide initial training to pharmacists and shared templates from previous validated models. Pharmacy companies were responsible for navigation of all implementation within their company. Researchers analyzed the de-identified data from patients seeking point-of-care testing from the participating pharmacies. RESULTS: Participating pharmacies reported 661 visits for adult (age 18 and over) patients tested for influenza for GAS pharyngitis. For the GAS patients, 91 (16.9%) tested positive. For the Influenza patients, 22.9% tested positive and 64 (77.1%) testing negative. Access to care was improved as patients presented to the visit outside normal clinic hours for 38% of the pharmacy visits, and 53.7% did not have a primary care provider. CONCLUSION: A collaborative care model for managing patients with symptoms consistent with influenza or group A streptococcus can be successfully implemented, and improve access to care outside of normal clinic hours and for those without a regular primary care provider.