BackgroundRandomized trials evaluating programmed cell death protein 1 (PD-1) inhibitors in metastatic melanoma either permitted treatment for 2 years (pembrolizumab) or more (nivolumab). The optimal duration of therapy is currently unknown due to limited data, and shorter therapies may be effective.MethodsData of patients with metastatic cutaneous melanoma treated with single-agent PD-1 inhibitors at Huntsman Cancer Institute from January 1, 2015, to December 31, 2018, was reviewed to identify a continuous series of patients who made the joint decision with their provider to electively discontinue therapy at 1 year (>6 months and <18 months) in the setting of ongoing treatment response or disease stability. Patients were excluded if they received PD-1 inhibitors with other systemic therapy, had prior exposure to PD-1 therapy, or discontinued treatment due to disease progression or immune-related adverse event. Best objective response (BOR) per RECIST V.1.1 at treatment discontinuation, progression-free survival (PFS), and retreatment characteristics was analyzed.ResultsOf 480 patients who received PD-1 inhibitors, 52 met the inclusion criteria. The median treatment duration from first to the last dose was 11.1 months (95% CI 10.5 to 11.4). BOR was complete response in 13 (25%), partial response in 28 (53.8%), and stable disease in 11 (21.2%) patients. After a median follow-up of 20.5 months (range 3–49.2) from treatment discontinuation, 39 (75%) patients remained without disease progression, while 13 (25%) had progression (median PFS 3.9 months; range 0.7–30.9). On multivariable analysis, younger age, history of brain metastasis, and higher lactate dehydrogenase at the time of anti-PD-1 discontinuation were associated with recurrence. Patients with recurrent melanoma were managed with localized treatment, anti-PD-1 therapies, and BRAF-MEK inhibitors. All patients except one were alive at data cutoff.ConclusionIn this large real-world, observational cohort study, the majority of patients with metastatic melanoma after 1 year of anti-PD-1 therapy remained without progression on long-term follow-up. The risk of disease progression even in patients with residual disease on imaging was low. After prospective validation, elective PD-1 discontinuation at 1 year may reduce financial and immunotherapy-related toxicity without sacrificing outcomes.

10048 Background: Randomized trials of PDi in MM permitted treatment for 2 years (pembrolizumab) or more (nivolumab). However, the optimal treatment duration is unknown, and shorter courses may be effective. We reviewed clinical outcomes of pts who electively discontinued PDi at 1 year at our institution. Methods: We performed a real-world, observational cohort study of pts with MM treated with single-agent PDi from 1/1/2015 to 12/31/2018 at Huntsman Cancer Institute. This was a continuous series of pts who made the joint decision with their provider to electively discontinue PDi at 1 year ( > 6 mos and < 18 mos) in the setting of ongoing treatment response or disease stability. Exclusion criteria: PDi with other systemic therapy, discontinuation due to disease progression or immune-related adverse event, and PDi in neoadjuvant, adjuvant, or clinical trial settings. Local therapies, as in real-world, were allowed. Best objective response (BOR) per RECIST 1.1 at PDi discontinuation, progression-free survival (PFS) and retreatment characteristics were analyzed. Results: Of 485 pts who received PDi, 52 met inclusion criteria. Median age was 60.5 years and 26.9% were female. Median duration of PDi from first to last dose was 11.1 mos (95% CI 10.5 - 11.4). BOR was complete response in 13 (25%), partial response in 28 (53.8%), and stable disease in 11 (21.2%) pts. After median follow-up of 20.5 mos (range 3 - 49.2) from treatment discontinuation, 39 (75%) pts remained without disease progression (median PFS not reached). Only 13 (25%) pts progressed. Median time to progression after treatment discontinuation was 3.9 mos (range 0.7-30.9). Of the 13 pts, 7 immediately underwent successful localized treatment to the solitary site of progression (3 SRS/SBRT, 4 resection; followed by PDi in 2), 5 were retreated with PDi and 1 received BRAF/MEK followed by PDi. Retreatment with PDi controlled disease in all 5 pts. All pts except 1 were alive at data cut-off. Conclusions: In the largest continuous series of pts with MM who electively discontinued PDi after 1 year of treatment, the majority remained without progression on follow-up. Risk of disease progression even in pts with residual disease on imaging was low, and retreatment was effective. Strengths of our study include real-world cohort and treatment pattern analysis. Limitations include single-institution, retrospective design. After prospective validation, elective PDi discontinuation at 1 year may reduce financial and PDi-related toxicity without sacrificing outcomes.

Objective Oral tyrosine kinase inhibitors (TKIs) are first line therapy for chronic myeloid leukemia (CML). A complete cytogenetic response (CCyR) correlates with increased overall survival, however only 66%–88% of patients achieve CCyR after one year of TKI treatment. Because TKI therapy alone cannot eliminate CML stem cells, strategies aimed at achieving faster and deeper responses are needed to improve long-term survival. Metformin is a widely prescribed glucose-lowering agent for patients with diabetes and in preclinical studies, has been shown to suppress cell viability, induce apoptosis, and downregulate the mTORC1 signaling pathway in imatinib resistant CML cell lines (K562R). This study aims to investigate the utility of metformin added to TKI therapy in patients with CML. Data Sources An observational study at an academic medical center (Salt Lake City, UT) was performed for adults with newly diagnosed, chronic-phase CML to evaluate attainment of CCyR from TKI therapy with or without concomitant metformin use. Descriptive analyses were used to describe baseline characteristics and attainment of response to TKI therapy. Data Summary Fifty-nine patients were evaluated. One hundred percent (5 of 5) in the metformin group and 73.6% (39 of 54) in the non-metformin group achieved CCyR. Approximately 20% of patients in both groups relapsed (defined by a loss of CCyR during study) after a median 34.5 months of follow-up. Conclusions Future research is warranted to validate these findings and determine the utility of metformin added to TKI therapy.