Major pathologic response on biopsy (MPRbx) in patients with advanced melanoma treated with anti-PD-1: evidence for an early, on-therapy biomarker of response.

Major pathologic response on biopsy (MPRbx) in patients with advanced melanoma treated with anti-PD-1: evidence for an early, on-therapy biomarker of response.

Publication date: Apr 01, 2019

With increasing anti-PD-1 therapy use in patients with melanoma and other tumor types, there is interest in developing early on-treatment biomarkers that correlate with long-term patient outcome. An understanding of the pathologic features of immune-mediated tumor regression is key in this endeavor.

Histologic features of immune-related pathologic response (irPR) following anti-PD-1 therapy were identified on hematoxylin and eosin (H&E)-stained slides in a discovery cohort of pre- and on-treatment specimens from n = 16 patients with advanced melanoma. These features were used to generate an irPR score [from 0 = no irPR features to 3 = major pathologic response on biopsy (MPRbx, ≤10% residual viable tumor)]. This scoring system was then tested for an association with objective response by RECIST1.1 and overall survival in a prospectively collected validation cohort of pre- and on-treatment biopsies (n = 51 on-treatment at 4-week timepoint) from melanoma patients enrolled on the nivolumab monotherapy arm of CA209-038 (NCT01621490).

Specimens from responders in the discovery cohort had features of immune-activation (moderate-high TIL densities, plasma cells) and wound-healing/tissue repair (neovascularization, proliferative fibrosis) compared to nonresponders, (P ≤ 0.021, for each feature). In the validation cohort, increasing irPR score associated with objective response (P = 0.009) and MPRbx associated with increased overall survival (n = 51; HR 0.13; 95%CI, 0.054-0.31, P = 0.015). Neither tumoral necrosis nor pretreatment histologic features were associated with response. Eight of 16 (50%) of patients with stable disease showed irPR features, two of which were MPRbx, indicating a disconnect between pathologic and radiographic features at the 4-week on-therapy timepoint for some patients.

Features of immune-mediated tumor regression on routine H&E-stained biopsy slides from patients with advanced melanoma correlate with objective response to anti-PD-1 and overall survival. An on-therapy biopsy may be particularly clinically useful for informing treatment decisions in patients with radiographic stable disease. This approach is inexpensive, straightforward, and widely available.

Stein, J.E., Soni, A., Danilova, L., Cottrell, T.R., Gajewski, T.F., Hodi, F.S., Bhatia, S., Urba, W.J., Sharfman, W.H., Wind-Rotolo, M., Edwards, R., Lipson, E.J., and Taube, J.M. Major pathologic response on biopsy (MPRbx) in patients with advanced melanoma treated with anti-PD-1: evidence for an early, on-therapy biomarker of response. 24680. 2019 Ann Oncol (30):4.

Concepts Keywords
Biomarker Tumoral necrosis
Biomarkers Therapy melanoma tumor
Biopsies Week timepoint melanoma
Biopsy Residual viable tumor
Cohort Radiographic stable disease
Eosin Medicine
Fibrosis Clinical medicine
Hematoxylin Medical specialties
Histologic Immune system
Melanoma Cancer
Monotherapy Bristol-Myers Squibb
Necrosis Monoclonal antibodies
Neovascularization Melanoma
Plasma Cells RTT
Radiographic Nivolumab
Regression Biopsy
Tumor
Wound Healing

Semantics

Type Source Name
disease MESH melanoma
disease DOID melanoma
pathway BSID Melanoma
gene UNIPROT RPL17
disease MESH tumor
drug DRUGBANK Nivolumab
gene UNIPROT TLR1
disease MESH fibrosis
gene UNIPROT PGRMC1

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