Ghobrial et al. Page 344

Preclinical studies have revealed CXCR4 as a promising target in multiple myeloma (MM). In a Phase Ib/II clinical trial, Ghobrial and colleagues assessed ulocuplumab, a first-in-class anti-CXCR4 antibody, combined with lenalidomide or bortezomib plus dexamethasone in patients with relapsed MM. This treatment regimen had a favorable safety profile. Particularly in combination with lenalidomide-dexamethasone, ulocuplumab treatment resulted in at least a partial response in over half of patients, with an overall clinical benefit rate of 72.4% and a progression-free survival of over 22 months. Further studies on this treatment regimen are warranted.

Hui et al. Page 354

FGFR1 amplification is associated with poor prognosis and endocrine resistance in patients with HR+/HER2 breast cancer. Lucitanib is an oral multikinase inhibitor with selective activity against FGFR1-3 and VEGFR1-3. Hui and colleagues conducted a phase II trial of lucitanib treatment in patients with HR+/HER2 metastatic breast cancer. Most patients developed hypertension as a result of treatment. Observed overall response rates differed based on the presence of FGFR1 or 11a3 amplifications. Although the cohorts were small, exploratory biomarker analyses revealed that patients with high level FGFR1 amplification or overexpression had better overall response rates than those with low FGFR1 expression. Therefore, further study of lucitanib in patients with FGFR1 amplification may be warranted.

Bagley et al. Page 397

Clinical use of plasma cell-free DNA (cfDNA) has expanded rapidly in oncology; however, the role of plasma cfDNA in glioblastoma (GBM) remains uncertain. Bagley and colleagues designed a prospective cohort study to explore the clinical utility of plasma cfDNA in newly diagnosed GBM. Baseline plasma cfDNA concentration was independently associated with worse clinical outcomes, and longitudinal cfDNA fluctuations tended to track with radiographic tumor burden. Although tissue-plasma concordance was low for calling tumor somatic mutations, at least one mutation was detected in plasma for over half of patients. These results suggest that plasma cfDNA may have utility in GBM.

Perumal et al. Page 450

Tumor-specific mutations are ideal targets for cancer immunotherapy as they may be recognized as neoantigens by mature T cells. Perumal and colleagues demonstrate that neoantigens identified in multiple myeloma are immunogenic and can elicit T-cell–specific responses associated with clinical responses, even in relapsed and refractory myeloma patients. Their findings suggest that dynamic monitoring of neoantigen specific T cell responses could serve as a direct pharmacodynamics biomarker of immunotherapeutic interventions in myeloma and that shared neoantigens could be targeted for “off-the-shelf” approaches, including neoantigen targeting cancer vaccines.