Increasing data support the importance of preexisting host immune response and neoantigen burden for determining response to immune checkpoint inhibitors (ICIs). In lung cancer and melanoma, tumor mutational burden (TMB) has emerged as an independent biomarker for ICI response. However, the significance of TMB in breast cancer, particularly in the context of PD-L1 negativity, remains unclear. This report describes a patient with HER2-negative breast cancer with high TMB and an apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like (APOBEC) trinucleotide signature; her disease was refractory to multiple lines of treatments but achieved durable complete response using ICIs and capecitabine. Additional analysis of the tumor revealed a low amount of stromal tumor-infiltrating lymphocytes (sTILs) and PD-L1 negativity, reflecting a poor preexisting host immune response. In collaboration with Foundation Medicine, comprehensive genomic profiling from 14,867 patients with breast cancer with the FoundationOne test was evaluated. Using the cutoff of ≥10 mutations/megabase (mut/Mb) for high TMB, PD-L1 positivity and TMB-high populations were not significantly overlapping (odds ratio, 1.02; P=.87). Up to 79% of TMB-high tumors with >20 mut/Mb were PD-L1–negative. Our study highlights that despite having low TILs and PD-L1 negativity, some patients may still experience response to ICIs.
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Saranya Chumsri, Ethan S. Sokol, Aixa E. Soyano-Muller, Ricardo D. Parrondo, Gina A. Reynolds, Aziza Nassar and E. Aubrey Thompson
Abraham S. Kanate, Miguel-Angel Perales and Mehdi Hamadani
Eligibility assessment of a potential candidate for allogeneic hematopoietic cell transplantation (allo-HCT) is a complex yet vital component of pretransplant evaluation. Although no formal standardized consensus exists to guide this process, transplant centers follow institutional standard operating procedures and parameters to approve candidacy of an individual patient. Consideration for allo-HCT is dependent on a myriad of interrelated factors, including disease-related (eg, appropriate indication, disease status, prior therapies), patient-related (eg, age, functional status, frailty, comorbidities), psychosocial, and economic factors. A multidisciplinary approach is optimal for patient selection and requires the efforts of transplant coordinators, nurses, advanced practice providers, social workers, psychologists, financial specialists, and physicians. This article reviews the data and provides general guidelines that may be used in making an informed decision when evaluating a prospective candidate for allo-HCT. These recommendations are based on published data, expert commentary, reviews, and institutional practices. In the end, the eligibility assessment and decision to consider allo-HCT as the optimal choice of treatment for an individual patient are truly as much an “art” as it is the “science” of medicine, encompassing a multidisciplinary approach to minimize harm without compromising the curative potential—all essential doctrines of the Hippocratic Oath.
Ayman Saad, Marcos de Lima, Sarah Anand, Vijaya Raj Bhatt, Ryan Bookout, George Chen, Daniel Couriel, Antonio Di Stasi, Areej El-Jawahri, Sergio Giralt, Jonathan Gutman, Vincent Ho, Mitchell Horwitz, Joe Hsu, Mark Juckett, Mohamed Kharfan Dabaja, Alison W. Loren, MSCE, Javier Meade, Marco Mielcarek, Jonathan Moreira, Ryotaro Nakamura, Yago Nieto, Julianna Roddy, Gowri Satyanarayana, Mark Schroeder, Carlyn Rose Tan, Dimitrios Tzachanis, Jennifer L. Burns and Lenora A. Pluchino
Hematopoietic cell transplantation (HCT) involves the infusion of hematopoietic progenitor cells into patients with hematologic disorders with the goal of re-establishing normal hematopoietic and immune function. HCT is classified as autologous or allogeneic based on the origin of hematopoietic cells. Autologous HCT uses the patient’s own cells while allogeneic HCT uses hematopoietic cells from a human leukocyte antigen-compatible donor. Allogeneic HCT is a potentially curative treatment option for patients with certain types of hematologic malignancies, and autologous HCT is primarily used to support patients undergoing high-dose chemotherapy. Advances in HCT methods and supportive care in recent decades have led to improved survival after HCT; however, disease relapse and posttransplant complications still commonly occur in both autologous and allogeneic HCT recipients. Allogeneic HCT recipients may also develop acute and/or chronic graft-versus-host disease (GVHD), which results in immune-mediated cellular injury of several organs. The NCCN Guidelines for Hematopoietic Cell Transplantation focus on recommendations for pretransplant recipient evaluation and the management of GVHD in adult patients with malignant disease.
Victoria Sopik, Vasily Giannakeas and Steven Narod
Featured Updates to the NCCN Guidelines
Neha Mehta-Shah, Steven M. Horwitz, Stephen Ansell, Weiyun Z. Ai, Jeffrey Barnes, Stefan K. Barta, Mark W. Clemens, Ahmet Dogan, Kristopher Fisher, Aaron M. Goodman, Gaurav Goyal, Joan Guitart, Ahmad Halwani, Bradley M. Haverkos, Richard T. Hoppe, Eric Jacobsen, Deepa Jagadeesh, Matthew A. Lunning, Amitkumar Mehta, Elise A. Olsen, Barbara Pro, Saurabh A. Rajguru, Satish Shanbhag, Aaron Shaver, Andrei Shustov, Lubomir Sokol, Pallawi Torka, Carlos Torres-Cabala, Ryan Wilcox, Basem M. William, Jasmine Zain, Mary A. Dwyer, Hema Sundar and Youn H. Kim
Mycosis fungoides (MF) is the most common subtype of cutaneous T-cell lymphoma (CTCL), and Sézary syndrome (SS) is a rare erythrodermic and leukemic subtype of CTCL characterized by significant blood involvement. Although early-stage disease can be effectively treated predominantly with skin-directed therapies, systemic therapy is often necessary for the treatment of advanced-stage disease. Systemic therapy options have evolved in recent years with the approval of novel agents such as romidepsin, brentuximab vedotin, and mogamulizumab. These NCCN Guidelines Insights discuss the diagnosis and management of MF and SS (with a focus on systemic therapy).