Non-Hodgkin Lymphoma: New Approaches to Treatment and Care

The experience of living with non-Hodgkin lymphoma, and the efforts to understand and treat it, are increasingly being framed not as a battle, but as a complex game – specifically, chess. This shift in metaphor, promoted by Abbvie in collaboration with AIL (Associazione Italiana Contro le Leucemie-linfomi e mieloma), FIL (Federazione Italiana Linfomi), and GFIL (Gruppo Italiano Infermieri Linfomi), aims to represent the journey of patients and researchers as one of “attese, battute d’arresto e ripartenze” – waits, setbacks, and restarts – where every decision counts.

The campaign, “Scacco al linfoma. Un nuovo ponte tra la ricerca e la cura” (Checkmate to Lymphoma. A New Bridge Between Research and Care), highlights the potential of new therapeutic options, such as bispecific antibodies, to improve both treatment outcomes and quality of life for those affected by non-Hodgkin lymphoma. The initiative’s website provides information about lymphomas, patient stories, and expert interviews.

Non-Hodgkin Lymphomas: Indolent and Aggressive

Non-Hodgkin lymphomas encompass over 50 different forms, broadly categorized into indolent (slow-growing) and aggressive types. Approximately 45% of cases are indolent, often allowing patients to live with the condition for years. Aggressive lymphomas, while growing and spreading rapidly, frequently respond well to treatment, with over half of patients potentially achieving a cure. The most common aggressive subtype is diffuse large B-cell lymphoma (DLBCL), characterized by rapidly growing lymph nodes and potential involvement of organs beyond the lymphatic system, affecting an estimated 150,000 new cases globally and 4,400 in Italy annually.

Follicular lymphoma is the most prevalent indolent subtype. Prognosis is assessed using the FLIPI index, and the disease is marked by a high risk of relapse and progressive resistance to conventional therapies, leading to reduced progression-free survival with each subsequent treatment line. “These are two pathologies with different scenarios,” explains Marco Ladetto, Professor of Hematology at the University of Eastern Piedmont and Director of Hematology at the Azienda ospedaliera universitaria Santi Antonio e Biagio e Cesare Arrigo of Alessandria. “When we talk about relapse, we refer to a lymphoma that reappears even after achieving an optimal complete response. A refractory lymphoma is a condition where a patient does not respond to effective therapy.” Relapse in DLBCL typically occurs relatively early, within months or a few years of remission, while follicular lymphoma can experience quiescent cells surviving for extended periods, leading to relapse decades later.

Diffuse Large B-Cell Lymphoma: Challenges and Advances

Despite achieving durable responses and good cure rates in initial treatment for DLBCL, managing patients after relapse becomes increasingly complex. An appropriate care pathway is crucial, supported by a network that addresses the patient’s physical, nutritional, and emotional needs, as well as practical aspects of treatment and follow-up. “Expectations for patients are profoundly changing; for many, cure or a good quality of life is possible,” emphasizes Giuseppe Toro, National President of AIL. “Lymphomas remain complex diseases, and accepting a diagnosis and its impact on quality of life is challenging. Fortunately, innovative treatments like bispecific antibodies offer new possibilities, even for patients who have exhausted other options.” AIL’s mission is to support scientific research, provide practical assistance through AIL Houses and mobility services, offer psychological support, and navigate bureaucratic hurdles for patients, and caregivers.

Caterina Patti, Director of Oncohematology at the “Villa Sofia-Cervello” Hospitals in Palermo, notes that the advent of CAR-T cell therapy and bispecific antibodies has improved prospects for patients with relapsed/refractory DLBCL and follicular lymphoma. These therapies are not only more effective but also less toxic, improving patients’ daily lives. The introduction of these innovative therapies necessitates intensive monitoring and multidisciplinary teams to manage potential adverse events and standardize the diagnostic-therapeutic process.

The Role of Nurses and Patient Support Groups

From diagnosis onward, nurses and caregivers play a vital role in the clinical care of lymphoma patients. “The nurse, beyond their technical role, acts as a ‘bridge’ in communication,” says Giuliana Nepoti, head of the GIFIL Commission. “Patients often turn to nurses with questions they haven’t asked their doctors. Our role is to transform fear into awareness, educating patients to recognize warning signs and normalize the treatment process.” The care is comprehensive, starting at diagnosis and continuing through follow-up.

The type of lymphoma significantly impacts both treatment choices and quality of life. Challenges are both physical and emotional. “Shock at diagnosis, anxiety, isolation, loss of normalcy, and difficulties maintaining work and family routines are common,” comments Giuseppe Gioffré, a national representative of AIL and a patient advocate. Patient support groups provide a space to share fears, hopes related to new treatments, and help patients and caregivers adapt to changes in family dynamics and the complexities of care.

How Bispecific Antibodies are Used Today

Recent research has led to new treatment options. “Recently, there have been a number of innovations in immunotherapy,” clarifies Enrico Derenzini, Associate Professor of Hematology at the University of Milan and Director of the Division of Oncohematology and Stem Cell Transplantation at the European Institute of Oncology (IEO) in Milan. “The first is represented by CAR-T cell therapy, which can be potentially curative in about 40% of cases, but with a problem of resistance that affects 50%-60% of patients who do not respond or relapse, and long manufacturing times for the product, which is not immediately available. The other innovation is the arrival of bispecific antibodies, which are redesigning the treatment of follicular lymphoma and diffuse large B-cell lymphoma, which currently in Italy have an indication and reimbursement after at least two previous lines of treatment. Bispecific antibodies are another form of immunotherapy that bind to the T lymphocyte (CD3) on one side, the effector cells of the immune system, and to the neoplastic cells (CD20) on the other, redirecting the T lymphocytes against the lymphoma cells.”

In clinical trials, these antibodies have demonstrated complete remission rates of around 40% in DLBCL and over 60% in follicular lymphoma, with prolonged response durations – over 3 years in DLBCL and beyond 4 years in follicular lymphoma. Currently, these antibodies are used as monotherapy, but future developments are expected to involve earlier and combined use with other therapies, such as chemo-immunotherapy, immunomodulatory agents like lenalidomide, or antibody-drug conjugates.