Clin Cancer Res
-
Multicenter Study
FDA Approval Summary: Axicabtagene Ciloleucel for Relapsed or Refractory Large B-cell Lymphoma.
In October 2017, the FDA granted regular approval to axicabtagene ciloleucel, a CD19-directed chimeric antigen receptor (CAR) T-cell therapy, for treatment of adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy. Efficacy was based on complete remission (CR) rate and duration of response (DOR) in 101 adult patients with relapsed or refractory large B-cell lymphoma (median 3 prior systemic regimens) treated on a single-arm trial. Patients received a single infusion of axicabtagene ciloleucel, preceded by lymphodepleting chemotherapy with cyclophosphamide and fludarabine. ⋯ With a median follow-up of 7.9 months, the median DOR was not reached in patients achieving CR (95% CI, 8.1 months; not estimable, NE), whereas patients with partial remission had an estimated median DOR of 2.1 months (95% CI, 1.3-5.3). Among 108 patients evaluated for safety, serious adverse reactions occurred in 52%. Cytokine release syndrome and neurologic toxicities occurred in 94% and 87% of patients, respectively, leading to implementation of a risk evaluation and mitigation strategy.
-
Immune checkpoint inhibitors revolutionized the treatment of non-small cell lung cancer (NSCLC). However, only one-quarter of patients benefit from these new therapies. PD-L1 assessment and tumor mutational burden (TMB) are available tools to optimize use of checkpoint inhibitors but novel tools are needed. Exome sequencing could generate many variables but their role in identifying predictors of response is unknown. ⋯ Altogether, these data provide a validated biomarker that predicts the efficacy of nivolumab or pembrolizumab in patients with NSCLC. Our biomarker seems to be superior to PD-L1 labeling and TMB models.
-
Multicenter Study
FDA Approval: Blinatumomab for Patients with B-cell Precursor Acute Lymphoblastic Leukemia in Morphologic Remission with Minimal Residual Disease.
On March 29, 2018, the FDA granted accelerated approval for blinatumomab (Blincyto; Amgen, Inc.) for the treatment of adults and children with B-cell precursor acute lymphoblastic leukemia (BCP ALL) in first or second complete remission with minimal residual disease (MRD) greater than or equal to 0.1%. Blinatumomab is a CD3xCD19 bispecific antibody approved previously for the treatment of relapsed or refractory BCP ALL. The basis for this accelerated approval was a single-arm trial. ⋯ The safety profile for blinatumomab was established in prior studies, and no new safety signals were observed in the new population. Cytokine release syndrome and neurotoxicity remain significant risks. The FDA is requiring confirmation of clinical benefit in a randomized trial.
-
Colorectal cancers with deficient DNA mismatch repair (dMMR) are presumed to uniformly have dense lymphocytic infiltration that underlies their favorable prognosis and is critical to their responsiveness to immunotherapy, as compared with MMR-proficient (pMMR) tumors. We examined T-cell densities and their potential heterogeneity in a large cohort of dMMR tumors. ⋯ Tumor-infiltrating T-cell densities exhibited greater intertumoral heterogeneity among dMMR than pMMR colon cancers, with CD3+IM providing robust stratification of both dMMR and pMMR tumors for prognosis. Potentially, lower T-cell densities among dMMR tumors may contribute to immunotherapy resistance.
-
Osimertinib was initially approved for T790M-positive non-small cell lung cancer (NSCLC) and, more recently, for first-line treatment of EGFR-mutant NSCLC. However, resistance mechanisms to osimertinib have been incompletely described. ⋯ Osimertinib resistance is associated with diverse, predominantly EGFR-independent genomic alterations. Continuation of osimertinib after progression, alone or in conjunction with radiotherapy, may provide prolonged clinical benefit in selected patients.See related commentary by Devarakonda and Govindan, p. 6112.