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COVID-19 is reshaping oncology practice, clinical trials, and delivery of cancer care broadly, and these changes might endure well beyond the short- to mid-term of the active pandemic. Therefore, shifts in practice brought about by the pandemic must be accompanied by improved training and awareness, enhanced infrastructure, and evidence-based support if they are to harness the positives and offset the potential negative consequences of the impacts of COVID-19 on cancer care.

Risk of multiple myeloma is increased in African American (AA) populations compared with European American (EA) cohorts. Current estimates of risk of progression of monoclonal gammopathy of undetermined significance (MGUS) are based largely on studies in EA cohorts. Prospective analyses of this risk in AA cohorts are lacking.

Between 2003 and 2011, 331 eligible patients with IgG/A monoclonal gammopathy were enrolled in a prospective observational trial (SWOG S0120).

Of 331 eligible patients, 57 (17%) were of AA descent. The risk of transformation to clinical malignancy in AA patients was significantly lower than in non-AA cohort (2-year risk 5% vs. 15%; 5-year risk 13% vs. 24%; log-rank

= 0.047). Differences in risk were evident for both MGUS and asymptomatic multiple myeloma. Gene expression profile (GEP) of CD138-purified plasma cells revealed that all molecular multiple myeloma subsets can be identified in both cohorts. However, the proportion of patients with high-risk GEP risk score (GEP-70 gene risk > -0.26) was lower in the AA cohort (0% vs. 33%,

= 0.01). AA cohorts also have higher levels of antibodies against Epstein-Barr nuclear antigen-1 (EBNA-1;

< 0.001).

These data provide the first prospective evidence that multiple myeloma precursor states in AA patients may have lower risk of disease compared with non-AA counterparts with lower incidence of high-risk GEP and increased EBV seropositivity. Race-dependent differences in biology and clinical risk of gammopathy may impact optimal management of these patients.

These data provide the first prospective evidence that multiple myeloma precursor states in AA patients may have lower risk of disease compared with non-AA counterparts with lower incidence of high-risk GEP and increased EBV seropositivity. Race-dependent differences in biology and clinical risk of gammopathy may impact optimal management of these patients.

High-grade gliomas (HGGs) are central nervous system tumors with poor prognoses and limited treatment options. Vocimagene amiretrorepvec (Toca 511) is a retroviral replicating vector encoding cytosine deaminase, which converts extended release 5-fluorocytosine (Toca FC) into the anticancer agent, 5-fluorouracil. According to preclinical studies, this therapy kills cancer cells and immunosuppressive myeloid cells in the tumor microenvironment, leading to T-cell-mediated antitumor immune activity. Therefore, we sought to elucidate this immune-related mechanism of action in humans, and to investigate potential molecular and immunologic indicators of clinical benefit from therapy.

In a phase I clinical trial (NCT01470794), patients with recurrent HGG treated with Toca 511 and Toca FC showed improved survival relative to historical controls, and some had durable complete responses to therapy. As a part of this trial, we performed whole-exome DNA sequencing, RNA-sequencing, and multiplex digital ELISA measurements on tumor and blood samples.

Genetic analyses suggest mutations, copy-number variations, and neoantigens are linked to survival. Quantities of tumor immune infiltrates estimated by transcript abundance may potentially predict clinical outcomes. Peak values of cytokines in peripheral blood samples collected during and after therapy could indicate response.

These results support an immune-related mechanism of action for Toca 511 and Toca FC, and suggest that molecular and immunologic signatures are related to clinical benefit from treatment.

These results support an immune-related mechanism of action for Toca 511 and Toca FC, and suggest that molecular and immunologic signatures are related to clinical benefit from treatment.

Tebentafusp is a first-in-class bispecific fusion protein designed to target gp100 (a melanoma-associated antigen) through a high affinity T-cell receptor (TCR) binding domain and an anti-CD3 T-cell engaging domain, which redirects T cells to kill gp100-expressing tumor cells. 2-APV nmr Here, we report a multicenter phase I/II trial of tebentafusp in metastatic melanoma (NCT01211262) focusing on the mechanism of action of tebentafusp.

Eighty-four patients with advanced melanoma received tebentafusp. Treatment efficacy, treatment-related adverse events, and biomarker assessments were performed for blood-derived and tumor biopsy samples obtained at baseline and on-treatment.

Tebentafusp was generally well-tolerated and active in both patients with metastatic uveal melanoma and patients with metastatic cutaneous melanoma. A 1-year overall survival rate of 65% was achieved for both patient cohorts. On-treatment cytokine measurements were consistent with the induction of IFNγ pathway-related markers in the periphery antafusp.

Combined axitinib/pembrolizumab is approved for advanced renal cell carcinoma (aRCC). This exploratory analysis examined associations between angiogenic and immune-related biomarkers and outcomes following axitinib/pembrolizumab treatment.

Prospectively defined retrospective correlative exploratory analyses tested biospecimens from 52 treatment-naïve patients receiving axitinib and pembrolizumab (starting doses 5 mg twice daily and 2 mg/kg respectively, every 3 weeks). Tumor tissue, serum, and whole blood samples were collected at baseline, at cycle 2 day 1 (C2D1), and end of treatment (EOT) for blood-based samples. Clinical outcomes were objective response rate (ORR) and progression-free survival (PFS).

Higher baseline tumor levels of CD8 showed a trend toward longer PFS (HR 0.4;

= 0.091). Higher baseline serum levels of CXCL10 (

= 0.0197) and CEACAM1 (

= 0.085) showed a trend toward better ORR and longer PFS, respectively. Patients for whom IL6 was not detected at baseline had longer PFS versus patients for whom it was detected (HR 0.