In 2021 and 2022, two immune checkpoint inhibitors received FDA approval in the neoadjuvant setting for the treatment of early-stage triple negative breast cancer (TNBC) and non–small cell lung cancer (NSCLC). Several more studies have since indicated the benefits, and challenges, of administering neoadjuvant immunotherapy prior to definitive surgery in the gastrointestinal, head and neck, and cutaneous realms. In addition, numerous ongoing phase II and phase III trials are investigating outcomes of neoadjuvant immune treatment in early-stage disease. As such, it is anticipated that more immune checkpoint inhibitors will receive approval for various neoadjuvant indications in the next several years. Medical oncologists, surgeons, and other providers in a multidisciplinary cancer care team will be presented with alternate treatment paradigms and clinical decisions regarding upfront surgery versus neoadjuvant treatment. Here, we describe the current evidence supporting use of immune checkpoint inhibitors for neoadjuvant treatment, ongoing studies, and clinical considerations of this treatment approach.

Near early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) is a rare hematologic malignancy, for which second line therapeutic options are limited. T-cell leukemias are also rarely associated with leukemia cutis, which is more often seen in leukemias of myeloid origin. We present the case of an adult male diagnosed with near ETP-ALL, with IDH2 and DNMT3A mutations, suggestive of a myeloid origin, and leukemia cutis. After the patient progressed on hyper-CVAD and nelarabine, we treated him with the BCL-2 inhibitor venetoclax and the hypomethylating agent decitabine. The regimen induced a rapid bone marrow response and resolution of the leukemia cutis.

Background/Objectives: Immune checkpoint inhibitors (ICIs) are frontline treatment for advanced Merkel Cell Carcinoma (MCC), regardless of viral status. Frontline ICIs provide durable benefit to only half of patients, highlighting a need for alternative therapies. In this study, the objective is to leverage whole exome sequencing (WES) and transcriptome sequencing (WTS) to distinguish genomic alterations associated with ICI response. Investigate differential genomic alterations between virus-positive (VP) and virus-negative (VN)-MCC to identify novel therapeutic targets. Methods: A total of 95 MCC cases underwent WES and WTS. Utilizing computational pipelines applied to WES, we identified viral status and tumor mutational burden (TMB). RNA-seq data was used to characterize the immune microenvironment. Results: Of 95 MCC cases, 57 (60%) were VP-MCC and 38 (40%) were VN-MCC. Median TMB was higher in VN-MCC (27.5 vs. 1 Muts/Mb). Mutations in TP53, RB1, NOTCH1, KMTD2, KMT2C, and PIK3CA were primarily found in VN-MCC. MAPK Pathway Activity Score, NK cell infiltration, and the immune checkpoint gene CD276 in VN-MCC tumors were upregulated. No overall survival (OS) difference was identified between VP and VN-MCC, even after ICIs. Conclusions: MCC oncogenesis and treatment response transcend viral status. While mutational analysis confirms previous findings, assessment of the transcriptome and tumor microenvironment suggests alternate therapeutic targets.

Background: There exists an unmet clinical need to define definitive management strategies for patients with locally advanced non-melanoma skin cancers (NMSC), particularly if not amenable to surgical resection. Methods: We retrospectively reviewed a case series of locally advanced unresectable NMSC treated with induction systemic treatment followed by response-adapted consolidative radiation. Results: We identified 15 patients who met study criteria, including seven with basal cell carcinoma (BCC), six with cutaneous squamous cell carcinoma (CSCC), and two with Merkel cell carcinoma (MCC). Clinical complete response (CR) by physical examination was observed in all 15 patients. No locoregional or distant recurrences were observed in any histologic subtype after completion of radiation (median follow-up from completion of radiation: 18.1 months BCC, 22.5 months CSCC, 22.7 months MCC). The median duration of observed response (DOOR), measured from first clinical response was 26.9 months (26.2 BCC, 29.4 CSCC, 27.1 MCC). Radiation treatment volumes were response-adapted with median gross tumor volume reduction of 55.3% (15.3%–100%). Median treatment-free response was 20.5 months. No unexpected systemic therapy related toxicities were identified. Conclusions: In this single-institution retrospective case series, induction systemic therapy followed by response-adapted consolidative radiation was feasible and associated with durable disease control in selected patients with locally advanced unresectable NMSC.