Extended duration of treatment using reduced-frequency dosing of anti-PD-1 therapy in patients with advanced melanoma and Merkel cell carcinoma.

BACKGROUND: Optimal duration of treatment (DoT) with immune checkpoint inhibitors (ICI) in metastatic cancers remains unclear. Many patients, especially those without radiologic complete remission, develop progressive disease after ICI discontinuation. Extending DoT with ICI may potentially improve efficacy outcomes but presents major logistical and cost challenges with standard frequency dosing (SFD). Receptor occupancy data supports reduced frequency dosing (RFD) of anti-PD-1 antibodies, which may represent a more practical and economically viable option to extend DoT. METHODS: We conducted a retrospective study of patients with metastatic melanoma and Merkel cell carcinoma (MCC), who received ICI at RFD administered every 3 months, after initial disease control at SFD. We evaluated efficacy, safety, and cost-savings of the RFD approach in this cohort. RESULTS: Between 2014 and 2021, 23 patients with advanced melanoma (N = 18) or MCC (N = 5) received anti-PD-1 therapy at RFD. Median DoT was 1.1 years at SFD and 1.2 years at RFD. The 3 year PFS after start of RFD was 73% in melanoma and 100% in MCC patients, which compare favorably to historical control rates. In the subset of 15 patients who received at least 2 years of therapy, total savings amounted to $1.1 million in drug costs and 384 h saved despite the extended DoT (median 3.4 years), as compared to the calculated cost of 2 years at SFD. CONCLUSIONS: ICI administration at RFD can allow extension of treatment duration, while preserving efficacy and reducing logistical and financial burden. RFD approach deserves further exploration in prospective clinical trials.

Outpatient intensive induction chemotherapy for acute myeloid leukemia and high-risk myelodysplastic syndrome.

To improve patient quality of life and reduce health care costs, many conditions formerly thought to require inpatient care are now treated in the outpatient setting. Outpatient induction chemotherapy for acute myeloid leukemia (AML) may confer similar benefits. This possibility prompted a pilot study to explore the safety and feasibility of intensive outpatient initial or salvage induction chemotherapy administration for adults with AML and high-risk myelodysplastic syndrome (MDS). Patients with no significant organ dysfunction and a treatment-related mortality (TRM) score corresponding to a day 28 mortality rate of <5% to 10% were eligible for study. Patients were treated as outpatients with daily evaluation by providers and only admitted to the hospital if mandated by complications. Twenty patients were consented, and 17 were treated. Eight patients received initial induction chemotherapy and 9 received salvage induction chemotherapy. Fourteen patients completed induction chemotherapy administration in the outpatient setting (82.4%; exact 95% confidence interval [CI], 55.8-95.3). Three patients were admitted during the course of chemotherapy administration, 2 for neutropenic fever and 1 for grade 3 mucositis. No patients died within 14 days of the initiation of induction chemotherapy (exact 95% CI, 0-22.9). Results of this pilot study suggest it is feasible to complete outpatient induction chemotherapy in select patients with AML and high-risk MDS. A team including nurses, social workers, medical providers, and pharmacists was key to the successful implementation of outpatient induction.