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As targeted therapy in B-cell lymphomas rapidly expands beyond anti-CD20 monoclonal antibodies, many newer types of agents are in various stages of development. During his presentation at the NCCN 20th Annual Conference, Dr. Andrew D. Zelenetz explored many of them, including the newer immunoconjugates, the Bruton's tyrosine kinase inhibitor ibrutinib, agents targeting apoptosis such as venetoclax (ABT-199), the immunomodulator lenalidomide, and novel immune checkpoint inhibitors such as nivolumab. To improve outcomes in patients with B-cell lymphomas, these therapies either target the tumor cells and their pathways or focus on the microenvironment and immune modulation.

Although complex, biologic agents are key components of modern therapy in multiple disciplines, particularly oncology. However, despite the fact that biosimilars (eg, filgrastim‐sndz, bevacizumab‐awwb, trastuzumab‐dkst, rituximab-abbs) have been approved in the United States, many clinicians are poorly informed about their unique pathway for approval. At the NCCN 2019 Annual Congress: Hematologic Malignancies, Dr. Andrew D. Zelenetz, Memorial Sloan Kettering Cancer Center, outlined important issues regarding the use of biosimilars, including extrapolation, interchangeability, and naming.

A host of new therapies are now available for treating patients with chronic lymphocytic leukemia (CLL) in both the upfront and relapsed or refractory settings. Although the optimal use of these agents is still being defined, established and emerging prognostic markers aid in the selection of appropriate treatment with the best chance of success. At the NCCN 22nd Annual Conference, Dr. Andrew Zelenetz discussed the role of the CLL-International Prognostic Index for risk stratification, reviewed optimal first-line therapy options, and then presented updated clinical trial data on the novel agents being used in the relapsed or refractory setting. The hope is that chronic therapy will be replaced by combinations that provide high rates of minimal residual disease negativity with durable remissions.

During his presentation at the NCCN 19th Annual Conference, Dr. Andrew D. Zelenetz reviewed the updates to the 2014 NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Non-Hodgkin’s Lymphomas. Dr. Zelenetz first discussed the updates for diffuse large B-cell lymphoma (DLBCL), focusing primarily on the emergence of MYC-positive DLBCL; the limited role of imaging in early-stage disease; new treatment options; the challenge of tumor heterogeneity; and the impact of cell of origin in the selection of future therapies. Then, on behalf of Dr. Steven Horwitz, Dr. Zelenetz presented the new guidelines for primary cutaneous CD30+ T-cell lymphoproliferative disorders and T-cell large granular lymphocytic leukemia.

CAR T cells have demonstrated activity in relapsed/refractory non-Hodgkin lymphoma, including diffuse large B-cell lymphoma (DLBCL), indolent non-Hodgkin lymphoma, and mantle cell lymphoma. For patients with chemorefractory disease, CAR T cells can provide a durable complete response in a portion of patients, which represents a major advance in the field. For patients with chemosensitive disease, however, additional data are needed to determine whether CAR T cells are preferable to conventional approaches. Studies in DLBCL have shown that patients experiencing a PET-positive partial response after second-line chemotherapy have long-term outcomes after high-dose therapy and autologous stem cell rescue that are similar to CAR T-cell therapy, with decreased toxicity and cost. Alternative third-line options such as tafasitamab/lenalidomide and bispecific antibodies may also have a role for patients with chemorefractory disease.

As biologics go off-patent, the field of oncology is grappling with incorporating biosimilars. These are highly similar (but not generic versions of) biologic agents, and they are approved based on showing “near fingerprint identity” in structure and potency. Their introduction is expected to increase competition and lower treatment costs. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Myeloid Growth Factors has incorporated the first biosimilar approved in the United States, filgrastim-sndz, into its recommendations. At the NCCN 21st Annual Conference, Andrew D. Zelenetz, MD, PhD, provided an overview of biosimilars, describing the process of their development and approval; Pamela S. Becker, MD, PhD, discussed the NCCN Guidelines recommendations for the use of filgrastim-sndz and of tbo-filgrastim, which was approved in the United States as a true biologic agent. The use of tbo-filgrastim can be somewhat confusing, as it does not have the same indications as the other growth factors.

Non-Hodgkin’s lymphomas (NHL) represent a diverse set of diseases, with different treatment pathways based on the stage and type of hematologic cancer. In their presentation at the NCCN 18th Annual Conference, Dr. Jeremy Abramson and Dr. Andrew D. Zelenetz discuss 3 specific B-cell NHLs: follicular lymphoma, mantle cell lymphoma, and chronic lymphocytic leukemia. They provided an overview of the treatment strategies for patients with these hematologic malignancies, and offered highlights from recent clinical trials supporting these recommendations.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) describe a continuum of cancer care in the United States, from initial diagnosis through treatment and referral to hospice beyond treatment. However, in many other countries, there are no regional or national clinical practice guidelines. In 2008, the NCCN-MENA (Middle East and North Africa) project was launched to adapt the NCCN Guidelines to this part of the world. During their joint presentation at the NCCN 19th Annual Conference, Dr. Ali Bazarbachi and Dr. Andrew D. Zelenetz explored the modification process of NCCN Guidelines for MENA and shared examples of how it improved the care of patients with adult T-cell leukemia or lymphoma and younger patients with diffuse large B-cell lymphoma—regardless of where they live.

Much has changed in the treatment of cancer since the first NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) were rolled out for 8 different tumor types in November 1996. NCCN Guidelines now include involved algorithms often containing multiple treatment alternatives and detailed pathways of care that depend on more-specific patient characteristics and molecular tumor diagnostics. With 47 different individual NCCN panels, all members of the cancer care team are now better informed than ever to guide patients through the often complex decision-making required to improve the odds of successful outcomes. At the NCCN 20th Annual Conference, a distinguished panel assembled to take a closer look at these invaluable clinical practice guidelines, first glancing backward to how it all started and then forward to explore the key ingredients of trustworthy guidelines.