ABSTRACT
Background: Recent studies have shown 5-yr recurrence rates for Stage IIB and IIC melanoma of up to 46%. These high-risk patients currently have few options for adjuvant therapy to prevent this inevitable recurrence, with the only FDA approved therapy being high-dose interferon-alfa, which is quite toxic. However, there are now immunotherapies (anti-PD1) and targeted therapies (anti-BRAF and anti-MEK combinations) which are approved as adjuvants for Stage III patients, some of whom will have a lower baseline recurrence risk than those with Stage IIB/IIC melanoma. We sought to determine if adjuvant PD1 inhibition with nivolumab (N) would improve the recurrence free survival (RFS) compared to historical RFS rates. Methods: Our study (NCT03405155) is a single-arm, open label, multicenter, phase 2 clinical trial evaluating RFS at 24 months in patients with Stage IIB/IIC melanoma on treatment with N at 480 mg IV every 4 weeks for 12 cycles. Overall survival is a secondary endpoint. Associated translational research includes circulating tumor cell DNA and immune correlates. Results: Twenty three patients with Stage IIB and three patients with Stage IIC melanoma were enrolled onto the study and received at least one dose of N. At data cutoff, 22 patients remain in follow up, as four patients withdrew consent at different time points in the study - one patient after one dose who wished to discontinue, one due to concern for COVID and need for repeat visits, one due to insurance issues, and one due to recurrence and wish to discontinue (which was captured in study data and RFS calculations). Seventeen patients have been on the clinical trial for at least two years with nine patients having finished treatment but with less than two years follow-up;the median follow-up is currently 21.9 months. Two patients demonstrated melanoma recurrence, one after receiving cycle six of N and another one year after completing treatment, resulting in a 87.8% RFS (90% CI (64.2%-96.3%) at 2 years, compared to the historical RFS at 2 years of 70%. No N related serious adverse events (SAEs) were observed, with only 2% Grade 3 AEs observed (varied and unrelated to treatment) and all others were Grade 1-2, including 21% GI, 18% cutaneous, and 10% musculoskeletal, respiratory, and fatigue, each;overall, 2% of these Grade 1-2 AEs were treatment related. Conclusions: Our preliminary results show a trend towards improved RFS in patients with Stage IIB/IIC melanoma treated with nivolumab. The cohort has not reached a minimum follow up of at least 2 years for RFS;patients are continuing to be monitored. On study, we observed the expected adverse events, without evidence of new toxicities. Data maturation will reveal the full effect of adjuvant N on disease relapse and overall survival and distant metastasis-free survival in stage IIB/IIC melanoma patients.
ABSTRACT
New York-Presbyterian Hospital and Columbia University Irving Medical Center were heavily impacted by the COVID-19 pandemic. Various measures were taken in an effort to ensure patient and staff safety. The management of patients with complex dermatological oncologic conditions, such as cutaneous lymphomas was especially challenging. We retrospectively reviewed the charts of the patients with cutaneous lymphomas who had COVID-19 (n=7) as well as those who did not have COVID-19 (n=26) from March to September 2020. Due to safety protocols, 4/7 (57%) patients who contracted COVID-19 experienced a treatment interruption. Three patients had no treatment interruptions because the timing of their COVID-related illness and scheduled treatments did not overlap. Treatment was delayed for a mean 2.1 months (range: 10 days - 4 months). Two out of four (50%) patients with treatment delays experienced disease relapse. Of the patients who did not have COVID-19, 12 patients experienced treatment delays, and ten (83.3%) of those patients experienced disease progression or relapse. Fourteen patients continued in hospital treatments with no delay, and 2 (14.3%) patients experienced disease progression or relapse. Of the total patients included in this review, 16 (48.5%) experienced a treatment. Delay. Twelve patients (12/16 or 75%) had disease relapse or progression following treatment delays. In contrast, among the 17 patients who did not experience treatment delay, 4 (23.5%) patients had relapse or progression of disease. Treatment delay was associated with a significant risk of disease relapse or progression (p=0.0053). No hospital-related cases of COVID-19 were recorded during the six-month capture period. Treatment interruptions are associated with negative clinical outcomes. Established safety protocols are effective in preventing infections during therapy for cutaneous lymphomas. We do not recommend altering treatment regimens for patients with cutaneous lymphomas if safety protocols can be assured.