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Substantial progress has been made in the clinical management of patients with follicular lymphoma over the past 2 decades. However, the role of autologous and allogeneic stem cell transplantation in these patients remains controversial. Myeloablative chemotherapy or radioimmunotherapy supported by autologous hematopoietic cell transplantation has been shown to lead to a longer progression-free survival and, in some studies, improved survival over standard therapy. However, in the era of rituximab-based therapies used as part of induction or salvage, these historical trials may not be representative. Allogeneic stem cell transplantation offers the advantages of a tumor-free graft and some immunologic graft-versus-lymphoma effects. However, fully myeloablative transplants have high morbidity and mortality rates. Dose-reduced conditioning regimens followed by allogeneic hematopoietic cell transplantation have substantially reduced treatment-related mortality and perhaps will produce better outcomes long-term. This article outlines some historical information regarding stem cell transplantation for follicular lymphoma and discusses recent modifications that may improve outcomes, such as adding radioimmunotherapy to autologous stem cell transplantation or using alternative dose-reduced regimens that could benefit patients with reduced toxicities.

REMS are a particularly important issue for oncology and the National Comprehensive Cancer Network (NCCN). A disproportionate number of drugs with complex REMS are used in patients with cancer or hematologic disorders. REMS policies and processes within oncology may act as a model for other clinical areas. A breadth of experience and access to a wide knowledge base exists within oncology that will ensure appropriate development and consideration of the practical implications of REMS. NCCN is uniquely positioned to assume a leadership role in this process given its status as the arbiter of high-quality cancer care based on its world-leading institutions and clinicians. Notwithstanding the potential benefits, the successful design, implementation, and analysis of the FDA's recent requirement for REMS for some high-risk drugs and biologics will present significant challenges for stakeholders, including patients, providers, cancer centers, manufacturers, payors, health information technology vendors, and regulatory agencies. To provide guidance to these stakeholders regarding REMS challenges, the NCCN assembled a work group comprised of thought leaders from NCCN Member Institutions and other outside experts. The Work Group identified challenges across the REMS spectrum, including the areas of standardization, development and assessment of REMS programs, medication guides, provider knowledge and impact on prescribing, provider burden and compensation, and incorporation of REMS into clinical practice.

Diffuse large B-cell lymphomas (DLBCLs) and follicular lymphoma (FL) are the most common subtypes of B-cell non-Hodgkin’s lymphomas in adults. Histologic transformation of FL to DLBCL (TFL) occurs in approximately 15% of patients and is generally associated with a poor clinical outcome. Phosphatidylinositol 3-kinase (PI3K) inhibitors have shown promising results in the treatment of relapsed/refractory FL. CAR T-cell therapy (axicabtagene ciloleucel and tisagenlecleucel) has emerged as a novel treatment option for relapsed/refractory DLBCL and TFL. These NCCN Guidelines Insights highlight important updates to the NCCN Guidelines for B-Cell Lymphomas regarding the treatment of TFL and relapsed/refractory FL and DLBCL.

In the last decade, a better understanding of the molecular pathogenesis of B-cell non-Hodgkin lymphomas has resulted in the development of novel targeted therapies, such as small molecule inhibitors of select kinases in the B-cell receptor pathway, antibody–drug conjugates, and small molecules that target a variety of proteins (eg, CD-19, EZH2, and XPO-1–mediated nuclear export). Anti-CD19 CAR T-cell therapy, first approved for relapsed/refractory (R/R) diffuse large B-cell lymphoma, has also emerged as a novel treatment option for R/R follicular lymphoma and mantle cell lymphoma. These NCCN Guideline Insights highlight the new targeted therapy options included in the NCCN Guidelines for B-Cell Lymphomas for the treatment of R/R disease.

Peripheral T-cell lymphomas (PTCLs) represent a relatively uncommon heterogeneous group of non-Hodgkin's lymphomas (NHLs) with an aggressive clinical course and poor prognosis. Anthracycline-based multiagent chemotherapy with or without radiation therapy followed by first-line consolidation with high-dose therapy followed by autologous stem cell rescue (HDT/ASCR) is the standard approach to most of the patients with newly diagnosed PTCL. Relapsed or refractory disease is managed with second-line systemic therapy followed by HDT/ASCR or allogeneic stem cell transplant, based on the patient's eligibility for transplant. In recent years, several newer agents have shown significant activity in patients with relapsed or refractory disease across all 4 subtypes of PTCL. These NCCN Guideline Insights highlight the important updates to the NCCN Guidelines for NHL, specific to the management of patients with relapsed or refractory PTCL.

Diffuse large B-cell lymphomas (DLBCL) are now considered a heterogeneous group of distinct molecular subtypes (germinal center B-cell DLBCL, activated B-cell DLBCL, and primary mediastinal large B-cell lymphoma (PMBL) with varied natural history and response to therapy. In addition, a subset of patients with DLBCL have concurrent MYC and/or BCL2 gene rearrangements (double-hit lymphomas; DHL) and others have a dual expression of both MYC and BCL2 proteins (double-expressing DLBCL; DEL). The standard of care for the treatment of patients with PMBL, DHL, or DEL has not been established. Adequate immunophenotyping and molecular testing (in selected circumstances) are necessary for the accurate diagnosis of different subtypes of DLBCL. The NCCN Guidelines included in this issue, part of the NCCN Guidelines for non-Hodgkin's lymphomas, address the diagnosis and management of DLBCL and its subtypes.