April Salama

Positions:

Associate Professor of Medicine

Medicine, Medical Oncology
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

M.D. 2004

University of North Carolina - Chapel Hill

Internal Medicine

The University of Chicago

Hematology/Oncology

The University of Chicago

Grants:

Collaborative Success: Expanding Options for Patients with Melanoma

Administered By
Duke Cancer Institute
Awarded By
National Institutes of Health
Role
Project Lead
Start Date
End Date

A Multicenter, Open label, Phase III Extension Trial to Study the Long-term Safety and Efficacy in Participants with Advanced Tumors Who Are Currently on Treatment or in Follow-up in a Pembrolizumab Trial.

Administered By
Duke Cancer Institute
Awarded By
Merck Sharp & Dohme
Role
Principal Investigator
Start Date
End Date

INCB 24360-208 A Phase 1/2, Open-Label, Dose-Escalation, Safety, Tolerability, and Efficacy Study of Epacadostat and Nivolumab in Combination With Immune Therapies in Subjects With Advanced or Metastatic Malignancies (ECHO-208)

Administered By
Duke Cancer Institute
Awarded By
Incyte Corporation
Role
Principal Investigator
Start Date
End Date

A Phase 3, Randomized Study of Adjuvant Immunotherapy with Nivolumab Combined with Ipilimumab versus Nivolumab Monotherapy after Complete Resection of Stage IIIb/c/d or Stage IV Melanoma

Administered By
Duke Cancer Institute
Awarded By
Bristol-Myers Squibb Company
Role
Principal Investigator
Start Date
End Date

A Phase II Randomized, Open-label, Multi-center Study of the Safety and Efficacy of IMCgp100 Compared with Investigator's Choice in HLA-A*0201 Positive Patients with Previously Untreated Advanced Uveal Melanoma

Administered By
Duke Cancer Institute
Awarded By
Immunocore Limited
Role
Principal Investigator
Start Date
End Date

Publications:

NCCN Guidelines® Insights: Melanoma: Cutaneous, Version 2.2021.

Over the past few years, the NCCN Guidelines for Melanoma: Cutaneous have been expanded to include pathways for treatment of microscopic satellitosis (added in v2.2020), and the following Principles sections: Molecular Testing (added in v2.2019), Systemic Therapy Considerations (added in v2.2020), and Brain Metastases Management (added in v3.2020). The v1.2021 update included additional modifications of these sections and notable revisions to Principles of: Pathology, Surgical Margins for Wide Excision of Primary Melanoma, Sentinel Lymph Node Biopsy, Completion/Therapeutic Lymph Node Dissection, and Radiation Therapy. These NCCN Guidelines Insights discuss the important changes to pathology and surgery recommendations, as well as additions to systemic therapy options for patients with advanced disease.
Authors
Swetter, SM; Thompson, JA; Albertini, MR; Barker, CA; Baumgartner, J; Boland, G; Chmielowski, B; DiMaio, D; Durham, A; Fields, RC; Fleming, MD; Galan, A; Gastman, B; Grossmann, K; Guild, S; Holder, A; Johnson, D; Joseph, RW; Karakousis, G; Kendra, K; Lange, JR; Lanning, R; Margolin, K; Olszanski, AJ; Ott, PA; Ross, MI; Salama, AK; Sharma, R; Skitzki, J; Sosman, J; Wuthrick, E; McMillian, NR; Engh, AM
MLA Citation
Swetter, Susan M., et al. “NCCN Guidelines® Insights: Melanoma: Cutaneous, Version 2.2021.J Natl Compr Canc Netw, vol. 19, no. 4, Apr. 2021, pp. 364–76. Pubmed, doi:10.6004/jnccn.2021.0018.
URI
https://scholars.duke.edu/individual/pub1478544
PMID
33845460
Source
pubmed
Published In
J Natl Compr Canc Netw
Volume
19
Published Date
Start Page
364
End Page
376
DOI
10.6004/jnccn.2021.0018

Phase I trial of intratumoral PVSRIPO in patients with unresectable, treatment-refractory melanoma.

BACKGROUND: While programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1) antagonists have improved the prognosis for many patients with melanoma, around 60% fail therapy. PVSRIPO is a non-neurovirulent rhinovirus:poliovirus chimera that facilitates an antitumor immune response following cell entry via the poliovirus receptor CD155, which is expressed on tumor and antigen-presenting cells. Preclinical studies show that oncolytic virus plus anti-PD-1 therapy leads to a greater antitumor response than either agent alone, warranting clinical investigation. METHODS: An open-label phase I trial of intratumoral PVSRIPO in patients with unresectable melanoma (American Joint Committee on Cancer V.7 stage IIIB, IIIC, or IV) was performed. Eligible patients had disease progression on anti-PD-1 and V-raf murine sarcoma viral oncogene homolog B (BRAF)/mitogen activated protein kinase kinase (MEK) inhibitors (if BRAF mutant). The primary objective was to characterize the safety and tolerability of PVSRIPO. Twelve patients in four cohorts received a total of 1, 2 or 3 injections of PVSRIPO monotherapy, with 21 days between injections. RESULTS: PVSRIPO injections were well tolerated with no serious adverse events (SAEs) or dose-limiting toxicities (DLTs) reported. All adverse events (AEs) were grade (G) 1 or G2 (G1 pruritus most common at 58%); all but two PVSRIPO-treatment related AEs were localized to the injected or adjacent lesions (n=1 G1 hot flash, n=1 G1 fatigue). Four out of 12 patients (33%) achieved an objective response per immune-related response criteria (two observations, 4 weeks apart), including 4/6 (67%) who received three injections. In the four patients with in-transit disease, a pathological complete response (pCR) was observed in two (50%) patients. Following study completion, 11/12 patients (92%) reinitiated immune checkpoint inhibitor-based therapy, and 6/12 patients (50%) remained without progression at a median follow-up time of 18 months. CONCLUSION: Intratumoral PVSRIPO was well tolerated. Despite the limited number of PVSRIPO treatments relative to the overall lesion burden (67% patients>5 lesions), intratumoral PVSRIPO showed promising antitumor activity, with pCR in injected as well as non-injected lesions in select patients. TRIAL REGISTRATION NUMBER: NCT03712358.
Authors
Beasley, GM; Nair, SK; Farrow, NE; Landa, K; Selim, MA; Wiggs, CA; Jung, S-H; Bigner, DD; True Kelly, A; Gromeier, M; Salama, AK
MLA Citation
Beasley, Georgia M., et al. “Phase I trial of intratumoral PVSRIPO in patients with unresectable, treatment-refractory melanoma.J Immunother Cancer, vol. 9, no. 4, Apr. 2021. Pubmed, doi:10.1136/jitc-2020-002203.
URI
https://scholars.duke.edu/individual/pub1480357
PMID
33875611
Source
pubmed
Published In
Journal for Immunotherapy of Cancer
Volume
9
Published Date
DOI
10.1136/jitc-2020-002203

A Review of Immune-Mediated Adverse Events in Melanoma.

The use of checkpoint inhibitor-based immunotherapy has transformed the treatment landscape for melanoma as well as many other cancer types. With the ability to potentiate tumor-specific immune responses, these agents can result in durable tumor control. However, this activation of the immune system can lead to a unique constellation of side effects, distinct from other cancer therapies, collectively termed immune-mediated adverse events (irAEs). This review will focus on irAEs and guidelines for management related to the most clinically relevant checkpoint inhibitors, those that target programmed death receptor-1 (PD-1) and cytotoxic T lymphocyte antigen-4 (CTLA-4).
Authors
Kennedy, LB; Salama, AKS
MLA Citation
Kennedy, Lucy Boyce, and April K. S. Salama. “A Review of Immune-Mediated Adverse Events in Melanoma.Oncol Ther, vol. 7, no. 2, Dec. 2019, pp. 101–20. Pubmed, doi:10.1007/s40487-019-0096-8.
URI
https://scholars.duke.edu/individual/pub1452785
PMID
32699983
Source
pubmed
Published In
Oncol Ther
Volume
7
Published Date
Start Page
101
End Page
120
DOI
10.1007/s40487-019-0096-8

Pharmacological Wnt ligand inhibition overcomes key tumor-mediated resistance pathways to anti-PD-1 immunotherapy.

While immune checkpoint blockade is associated with prolonged responses in multiple cancers, most patients still do not benefit from this therapeutic strategy. The Wnt-β-catenin pathway is associated with diminished T cell infiltration; however, activating mutations are rare, implicating a role for autocrine/paracrine Wnt ligand-driven signaling in immune evasion. In this study, we show that proximal mediators of the Wnt signaling pathway are associated with anti-PD-1 resistance, and pharmacologic inhibition of Wnt ligand signaling supports anti-PD-1 efficacy by reversing dendritic cell tolerization and the recruitment of granulocytic myeloid-derived suppressor cells in autochthonous tumor models. We further demonstrate that the inhibition of Wnt signaling promotes the development of a tumor microenvironment that is more conducive to favorable responses to checkpoint blockade in cancer patients. These findings support a rationale for Wnt ligand-focused treatment approaches in future immunotherapy clinical trials and suggest a strategy for selecting those tumors more responsive to Wnt inhibition.
Authors
DeVito, NC; Sturdivant, M; Thievanthiran, B; Xiao, C; Plebanek, MP; Salama, AKS; Beasley, GM; Holtzhausen, A; Novotny-Diermayr, V; Strickler, JH; Hanks, BA
MLA Citation
DeVito, Nicholas C., et al. “Pharmacological Wnt ligand inhibition overcomes key tumor-mediated resistance pathways to anti-PD-1 immunotherapy.Cell Rep, vol. 35, no. 5, May 2021, p. 109071. Pubmed, doi:10.1016/j.celrep.2021.109071.
URI
https://scholars.duke.edu/individual/pub1470781
PMID
33951424
Source
pubmed
Published In
Cell Reports
Volume
35
Published Date
Start Page
109071
DOI
10.1016/j.celrep.2021.109071

Ipilimumab and Radiation in Patients with High-risk Resected or Regionally Advanced Melanoma.

PURPOSE: In this prospective trial, we sought to assess the feasibility of concurrent administration of ipilimumab and radiation as adjuvant, neoadjuvant, or definitive therapy in patients with regionally advanced melanoma. PATIENTS AND METHODS: Twenty-four patients in two cohorts were enrolled and received ipilimumab at 3 mg/kg every 3 weeks for four doses in conjunction with radiation; median dose was 4,000 cGy (interquartile range, 3,550-4,800 cGy). Patients in cohort 1 were treated adjuvantly; patients in cohort 2 were treated either neoadjuvantly or as definitive therapy. RESULTS: Adverse event profiles were consistent with those previously reported with checkpoint inhibition and radiation. For the neoadjuvant/definitive cohort, the objective response rate was 64% (80% confidence interval, 40%-83%), with 4 of 10 evaluable patients achieving a radiographic complete response. An additional 3 patients in this cohort had a partial response and went on to surgical resection. With 2 years of follow-up, the 6-, 12-, and 24-month relapse-free survival for the adjuvant cohort was 85%, 69%, and 62%, respectively. At 2 years, all patients in the neoadjuvant/definitive cohort and 10/13 patients in the adjuvant cohort were still alive. Correlative studies suggested that response in some patients were associated with specific CD4+ T-cell subsets. CONCLUSIONS: Overall, concurrent administration of ipilimumab and radiation was feasible, and resulted in a high response rate, converting some patients with unresectable disease into surgical candidates. Additional studies to investigate the combination of radiation and checkpoint inhibitor therapy are warranted.
Authors
Salama, AKS; Palta, M; Rushing, CN; Selim, MA; Linney, KN; Czito, BG; Yoo, DS; Hanks, BA; Beasley, GM; Mosca, PJ; Dumbauld, C; Steadman, KN; Yi, JS; Weinhold, KJ; Tyler, DS; Lee, WT; Brizel, DM
MLA Citation
Salama, April K. S., et al. “Ipilimumab and Radiation in Patients with High-risk Resected or Regionally Advanced Melanoma.Clin Cancer Res, vol. 27, no. 5, Mar. 2021, pp. 1287–95. Pubmed, doi:10.1158/1078-0432.CCR-20-2452.
URI
https://scholars.duke.edu/individual/pub1464016
PMID
33172894
Source
pubmed
Published In
Clinical Cancer Research
Volume
27
Published Date
Start Page
1287
End Page
1295
DOI
10.1158/1078-0432.CCR-20-2452