EHA Endorsement of ESMO Clinical Practice Guidelines for Newly Diagnosed and Relapsed Follicular Lymphoma
Authors: Marco Ladetto, Martin Dreyling
Journal: HemaSphere (2021)

EHA and ESMO recently agreed to collaborate on the production of European Guidelines for different hematological malignancies. As a first step, a number of completed guidelines have been reviewed by the corresponding EHA Scientific Working Groups in a standardized review process. The ESMO Clinical Practice Guidelines for diagnosis, treatment, and follow-up for Follicular Lymphoma released in the late 2020 in accordance with the ESMO standard operating procedures for Clinical Practice Guidelines development1,2 were recently endorsed by the EHA Lymphoma Working Group (LyG) and represent an example of this collaboration.3 Follicular lymphoma (FL) is the most common indolent lymphoma subtype in Europe. It is also the indolent lymphoma entity in which the largest body of high-quality evidence on treatment options has been accumulated over time, as opposed to other indolent subtypes where often there is a lack of well-conducted randomized phase III trials. It should be noted that grade IIIB FL is an aggressive subtype and is usually not considered in detail in the context of treatment guidelines for FL. The same applies to transformed FL Risk stratification at diagnosis remains a major subject of interest in FL. Clinical scores such as FLIPI and FLIPI 2 and PRIMA-PI provide simple and reliable tools for prognostic discrimination and might impact therapeutic decisions in the everyday clinical practice, as opposed to biological, PET-based, and minimal residual disease–based prognostication, which are investigated in clinical trials but are still not used in routine practice. Even although there is a well-recognized subgroup of patients with localized disease who are potential candidates for local curative treatment, the majority of FL patients presents with advanced disease. In this setting, the indication for watchful waiting for those subjects with asymptomatic low tumor burden disease still remains a very appropriate option in most cases. For those requiring treatment, immunochemotherapy is still considered the optimal approach. No single chemotherapy regimen has proved superior to others in terms of overall survival and choice should be based on patient conditions, priorities and prevention of long-term toxicity. Obinotuzumab-chemotherapy proved superior to rituximab-chemotherapy in terms of progression-free survival (PFS) without overall survival (OS) benefit. Based on its benefit on PFS, 2-year rituximab maintenance is usually applied following immunochemotherapy, but the increased COVID-19 infection risk has to be considered.4 Rituximab monotherapy and the rituximab-lenalidomide combination are considered for selected cases. The field of relapsed/refractory FL is even more rapidly evolving as therapeutic field. Here, a number of novel therapeutic approaches are implemented, even while several well-established treatments still find a place in specific clinical settings, making therapeutic decisions often difficult. Parameters affecting therapeutic decisions include number and type of previous treatment lines, duration of response (POD 24), tumor burden at relapse, and patient fitness. Such approaches include immunochemotherapy and also high-dose chemotherapy followed by autologous transplantation in selected settings. Nevertheless, the most rapidly evolving field is the use of biological treatments with the rituximab-lenalidomide combination becoming one of the most attractive combinations, as well as PI3K inhibitors, which appear to have substantial activity in relapsed/refractory FL. In this rapidly evolving therapeutic context, many institutions offer clinical trials with novel experimental agents including small molecules, T-cell engaging agents, as well as cellular therapies. All of these might represent very attractive options in selected patients. Thanks to the wide availability of therapeutic agents, the prognosis of FL has improved over the last decades, and patients might expect to enjoy prolonged long-term survival. In this context, careful evaluation of patient priorities should also be part of the treatment decision process, as well as careful consideration of prevention of both early and late toxicities, including secondary tumors and preservation of adequate organ functions. The current ESMO guidelines provide practical evidence-based guidance for clinicians in a rapidly evolving field. Already today, patients entering our clinic are facing a broad variety of different therapeutic options. In future years, additional targeted and biological approaches will further enrich our therapeutic armamentarium. Disclosures ML has grants and consulting fees from AbbVie, Acerta, Amgen, Archigen, ADC Therapeutics, Celgene, Gilead, J&J, Jazz, Roche, Sandoz, Takeda. MD has grants and consulting fees from AbbVie, AstraZeneca, Bayer, BeiGene, Celgene, Gilead, Jannsen, Novartis, Roche.