Serum albumin in cancer patients is associated with clinical outcomes. In a single-center retrospective study of 210 advanced NSCLC patients receiving immune checkpoint inhibitor (ICI) with or without chemotherapy as first-line therapy, we found a significant association of overall survival with pretreatment albumin and early albumin decrease in treatment with ICI monotherapy but not with chemoimmunotherapy. Cancer cachexia exhibits decreased albumin and associates with short overall survival (OS) in patients with non-small cell lung cancer (NSCLC), but whether on-treatment albumin changes associate with OS in NSCLC patients treated with immune checkpoint inhibitors (ICIs) and combination chemoimmunotherapy has not been thoroughly evaluated. We conducted a single-center retrospective study of patients with advanced NSCLC who received first-line ICI with or without chemotherapy between 2013 and 2020. The association of pretreatment albumin and early albumin changes with OS was evaluated using Kaplan-Meier method and Cox regression models. A total of 210 patients were included: 109 in ICI cohort and 101 in ICI+Chemo cohort. Within a median of 21 days from treatment initiation, patients with ≥10% of albumin decrease had significantly shorter OS compared to patients without albumin decrease in ICI cohort. Pretreatment albumin and albumin decrease within the first or second cycle of treatment were significantly and independently associated with OS in ICI cohort, but not in ICI+Chemo cohort. The lack of association between albumin and OS with the addition of chemotherapy was more pronounced among patients with ≥ 1% PD-L1 expression in subgroup analysis. Pretreatment serum albumin and early albumin decrease in ICI monotherapy was significantly associated with OS in advanced NSCLC. Early albumin change, as a routine lab value tested in clinic, may be combined with established biomarkers to improve outcome predictions of ICI monotherapy. The underlying mechanism of the observed association between decreased albumin and ICI resistance warrants further investigation.

Hairy cell leukemia (HCL) is a rare B-cell malignancy, and there is a need for novel treatments for patients who do not benefit from purine analogs. Ibrutinib, an oral agent targeting Bruton tyrosine kinase in the B-cell receptor signaling pathway, is highly effective in several malignancies. Its activity in HCL was unknown, so we conducted a multisite phase 2 study of oral ibrutinib in patients with either relapsed classic or variant hairy cell leukemia. The primary outcome measure was the overall response rate (ORR) at 32 weeks, and we also assessed response at 48 weeks and best response during treatment. Key secondary objectives were characterization of toxicity and determination of progression-free survival (PFS) and overall survival (OS). Thirty-seven patients were enrolled at 2 different doses (24 at 420 mg, 13 at 840 mg). The median duration of follow-up was 3.5 years (range, 0-5.9 years). The ORR at 32 weeks was 24%, which increased to 36% at 48 weeks. The best ORR was 54%. The estimated 36-month PFS was 73% and OS was 85%. The most frequent adverse events were diarrhea (59%), fatigue (54%), myalgia (54%), and nausea (51%). Hematologic adverse events were common: anemia (43%), thrombocytopenia (41%), and neutropenia (35%). Ibrutinib can be safely administered to patients with HCL with objective responses and results in prolonged disease control. Although the initial primary outcome objective of the study was not met, the observation of objective responses in heavily pretreated patients coupled with a favorable PFS suggests that ibrutinib may be beneficial in these patients. This trial was registered at www.clinicaltrials.gov as #NCT01841723.

Purpose: Treatment options are limited in patients with metastatic neuroendocrine neoplasms (NEN). We present the results for a phase II trial of combination nivolumab and temozolomide in patients with advanced NEN along with results of immune changes in peripheral blood. Patients and Methods: NCT03728361 is a nonrandomized, phase II study of nivolumab and temozolomide in patients with NEN. The primary endpoint was response rate using RECIST 1.1. Secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety. Immune profiling was performed by mass cytometry to evaluate the effect on peripheral blood immune cell subsets. Results: Among all 28 patients with NEN, the confirmed response rate was 9/28 [32.1%, 95% confidence interval (CI): 15.9–52.4]. Of 11 patients with lung NEN, the response rate was 64% (n = 7); there was a significant difference in responses by primary tumor location (lung vs. others, P = 0.020). The median PFS was 8.8 months (95% CI: 3.9–11.1 months), and median OS was 32.3 months (95% CI: 20.7—not reached months). Exploratory blood immune cell profiling revealed an increase in circulating CD8+ T cells (27.9% ± 13.4% vs. 31.7% ± 14.6%, P = 0.03) and a decrease in CD4+ T cells (59.6% ± 13.1% vs. 56.5% ± 13.0%, P = 0.001) after 2 weeks of treatment. LAG-3–expressing total T cells were lower in patients experiencing a partial response (0.18% ± 0.24% vs. 0.83% ± 0.55%, P = 0.028). Myeloid-derived suppressor cell levels increased during the study and did not correlate with response. Conclusions: Combination nivolumab and temozolomide demonstrated promising activity in NEN. See related commentary by Velez and Garon, p. 691