When every treatment counts: How clinical trials are changing the outlook for non

When every treatment counts: How clinical trials are changing the outlook for non-Hodgkin lymphoma patients By Willow Shah-Neville Add Labiotech as your Google Preferred Source 19 minutesmins September 7, 2026 19 minutesmins Share WhatsApp Twitter Linkedin Email Photo credits: National Cancer Institute (Unsplash) Add Labiotech as your Google Preferred Source Newsletter Signup - Under Article / In Page"*" indicates required fieldsCommentsThis field is for validation purposes and should be left unchanged.Subscribe to our newsletter to get the latest biotech news!By clicking this I agree to receive Labiotech's newsletter and understand that my personal data will be processed according to the Privacy Policy.*Company name*Job title*Business email* Andy Brown remembers breathlessness being the first sign; just the simple, unnerving fact that he could no longer keep up with his friend on his regular runs, despite usually “sailing around” together. It may have only been a small clue, one with plenty of other explanations, but for him it was the beginning of a long and arduous journey battling a cancer that affects around 13,747 people in the U.K. every year. This was during the run‑up to Christmas 2014. At first, Brown had no idea that the breathlessness was due to fluid leaking into the lining of his lung, collapsing the right side. And he certainly did not know that this, in turn, was due to an aggressive cancer growing quietly inside him, and that he was already in urgent need of treatment. By March 2015, he went to his GP. The chest X‑ray showed the collapsed lung immediately. What followed was a sequence of delays, missteps and missed opportunities that Brown still recounts with emotion. One doctor sent him home with antibiotics. Another had him waiting eight hours in a place alongside A&E for GP referrals, only to send him home again without being seen and telling him to come back in the morning. The next day his lung was drained and he was sent home to wait for an outpatient scan appointment. But just a week later he was back, his lung once again full of fluid, and he found himself arguing with an A&E consultant who wanted to discharge him after draining it. “I actually said to him, ‘I don’t believe there’s anybody competent in this hospital who can authorize a scan.’” Twenty minutes later, he was in the scanner. “I’m on the online groups for Lymphoma Action and the Follicular Lymphoma Foundation, and so many people have absolutely horrific stories of getting diagnosed,” said Brown. “I’m sure it’s not easy because a lot of the symptoms you go to the GP with could easily be other things. But I’m sure it could be an awful lot better than it is.” Suggested Articles Six bispecific antibody companies you should know about Two targets, one solution: The rise of bispecific antibodies The rise of trispecific antibodies: Biopharma’s next big bet after bispecifics Eight CAR-T cell therapy companies you should know about Eight in vivo CAR T biotechs to follow closely These were the difficult beginnings of a diagnosis that would shape the next decade of his life. Table of contentsWhen “slow‑growing” isn’t slow In April 2015, at the age of 56, Brown was diagnosed with follicular lymphoma – a form of non‑Hodgkin lymphoma often described as “indolent”, meaning slow‑growing. But the term can be misleading. Follicular lymphoma sits under the umbrella of non‑Hodgkin lymphoma because it arises from B cells, the immune cells responsible for producing antibodies. It typically grows gradually, and many patients can “watch and wait” for years before needing treatment. But Brown was not one of them. “In the early days, I didn’t feel I wanted to learn too much about it [follicular lymphoma] because I was very scared of what I’d find out,” he recalled. “But one of the clues, retrospectively, that I had a more difficult side of follicular was the fact that I needed urgent treatment and my disease was already very advanced and extensive.” Most people with follicular lymphoma notice a lump in the neck or armpit. Some are diagnosed after routine blood tests. Many begin treatment months or years later. But around 20% of patients have disease that behaves more aggressively – relapsing quickly, spreading extensively, and requiring repeated lines of therapy. “The extremes are enormous. And yet there is this perception that follicular is indolent,” said Brown. “But for 20% of people, it’s definitely not indolent. And I’m kind of just on the edge of the 20%.” His first treatment – R‑CVP chemotherapy followed by two years of rituximab maintenance – put him into remission. But he relapsed just a year after finishing maintenance. “That’s kind of the second clue,” he said. “How quickly you relapse after the first treatment… that lays the pattern as to whether you’re going to have more difficult disease or whether you’re going to have traditional indolent disease.” For Brown, the pattern was becoming unnervingly clear. Living with relapse Relapse changes everything. It changes how doctors talk to you. It changes how you think about time. It changes the options available – and the urgency with which you must choose between them. “It’s what they call fourth-line treatment,” explained Brown, describing the point he eventually reached. “They call the stage I’m at, they call it end‑of‑life disease, which is slightly rude, I would think – but that’s what they call it because you’re at fourth line.” After R‑CVP and maintenance came R‑CHOP, a stronger, second-stage chemotherapy. It worked. Then, four months later, he underwent an autologous stem cell transplant in Leeds. “It was an absolutely brilliant facility, and there was one wonderful doctor running the place; I can’t speak too highly of Dr. Rod Johnson,” said Brown. The transplant itself was gruelling: five days of intensive chemotherapy, isolation, weeks without a fully functioning immune system. “It just wipes you out and it takes a couple of months to get your strength back; when I first got home, I had to rest halfway up the stairs.” Even then, the procedure only bought him three more years, which, as he put it, “isn’t good.” Then came R² – lenalidomide plus rituximab – which gave him an extra year. “I was now beginning to realise that I had more of a problem with follicular lymphoma than most people,” he recalled. “Things were getting tricky, and I worried that options may be running out.” During this time, he began reading about emerging treatments: CAR‑T cell therapy and bispecific antibodies. He even raised a Parliamentary petition to make newer treatments more widely available. “It proved to be a steep learning curve,” he said. “I’d hoped to get some traction on social media, but quickly realized that a 60+ bloke talking about treatments would struggle to go viral. Then an election was called, and all petitions are wiped with a change of government.” In 2024 Brown relapsed again. After three partial deep vein thromboses (DVTs) in his leg, which “swelled up like a balloon,” and eventually having a scan that showed declining kidney function, Brown talked to a consultant, who told him they could either give him bendamustine plus rituximab – a standard option – or they could talk to The Christie, a specialist NHS single site cancer center in Manchester, to see if there were any clinical trials available. “So, I said, ‘yeah, let’s do that’ because I want to keep the bendamustine and rituximab chemo option in reserve for as long as I can, in case I need that.” With that decision, Brown kickstarted his journey through a clinical trial. When the next option is a clinical trial Clinical trials are often described as opportunities – a chance to access new treatments, contribute to research, or receive care at specialist centers. But for patients with relapsed lymphoma, they can also be lifelines. Brown was referred to The Christie in Manchester, one of Europe’s leading centers for lymphoma trials. “They are just amazing. Professor Kim Linton – she is just absolutely incredible…she’s one of the lymphoma professors, so they oversee the whole lymphoma unit,” explained Brown. Initially, he had hoped for a CAR‑T cell therapy trial. He met with a CAR‑T specialist, underwent hours of assessment, and learned that his kidney function – already compromised by his cancer pressing against the organ – might not withstand the process. The trial was also randomized: only half of participants would receive CAR‑T. “This was incredibly disappointing,” he said. “But I had to take their advice.” Then came another option: bispecific antibodies. The REFRACT trial was recruiting. After a scan and biopsy, Brown was confirmed eligible. REFRACT is a randomised trial: 50% of participants receive a new treatment, and 50% receive a standard option chosen beforehand. Brown knew what was at stake. “I didn’t dare tell my wife that I might not get the treatment. I just didn’t dare tell her,” he said, pausing with tangible emotion as he recalled the moment. Once he had been accepted onto the trial and had the necessary tests, the randomization result came through. Amazingly, he had been assigned to the experimental arm: epcoritamab combined with lenalidomide. “I felt like I’d won the ultimate lottery!” For Brown, that randomization carried a weight that is difficult to capture in the language of trial protocols. “Your whole life depends on that. Staying alive, you know, that means another, hopefully, three or four years of life that you might not get otherwise. For a flip of a computer coin.” The new treatment, epcoritamab – developed by Genmab and AbbVie – is a bispecific antibody designed to bring the immune system into direct contact with malignant B cells. Unlike conventional chemotherapy, which attacks rapidly dividing cells, a bispecific antibody works by recognizing two different targets. Epcoritamab binds to CD20 on the surface of B cells and CD3 on T cells, bringing the two together so that the T cell can attack the lymphoma cell. Brown stressed the enormous practical difference from his stem cell transplant; epcoritamab was delivered as a subcutaneous injection, with monitoring and blood tests around treatment, rather than requiring a prolonged hospital admission. “The most fantastic thing about bispecifics is that for me it was a really easy treatment. Very much easier than the chemotherapy and stem cell transplant I’d had over the years.” But getting the treatment still demanded a substantial commitment. Brown lives in Harrogate, around 75 miles from Manchester. During the trial, he travelled to The Christie repeatedly, usually leaving home at 5 a.m. to make it to his appointments. Over roughly three months, he estimates that he made more than 30 trips and put around 5,000 miles on his car. One night, with snow forecast, he drove to Manchester the evening before and stayed in a Premier Inn because he could not risk missing treatment. “It’s quite an exercise, but to stay alive, where wouldn’t you travel to?” That burden is an often-overlooked part of clinical research. A trial may offer access to a promising treatment, but participation can require repeated journeys, time away from work and family, and the ability to absorb costs that are not necessarily covered. For someone without a car, without a partner or family member who is able to help, or living much further from a major cancer center, Brown believes the practical barriers could make participation impossible. “Imagine somebody who lives a bit further away who didn’t have family and didn’t drive; it might mean you couldn’t do it.” A new era for follicular lymphoma treatment The importance of Brown’s experience extends beyond the outcome of his own trial. When he received epcoritamab through REFRACT, it was an investigational treatment in the U.K. Today, the drug – which was first approved for follicular lymphoma in the U.S. in June 2024 – occupies a very different position in the treatment landscape. In March 2026, NICE recommended epcoritamab as an option for adults with relapsed or refractory follicular lymphoma after two or more lines of systemic treatment. Under the recommendation, treatment is stopped after three years or earlier if the lymphoma progresses, and the drug is now available through the NHS in England, Wales, and Northern Ireland. The recommendation is based on evidence suggesting that epcoritamab is likely to extend the time patients live without their disease worsening and may extend overall survival compared to usual treatment. NICE also notes an important limitation: epcoritamab has not been directly compared in a clinical trial with usual treatments after two or more lines of systemic treatment, so the comparison relies on indirect evidence. The success of bispecific antibodies in follicular lymphoma shows just how promising these treatments can be, and the field is now asking whether they can be given even earlier in the treatment pathway. Results from the phase 3 EPCORE FL-1 trial, published in The Lancet in January 2026, found that epcoritamab combined with lenalidomide and rituximab improved progression-free survival and overall response rates compared with lenalidomide and rituximab alone in patients with relapsed or refractory follicular lymphoma. Meanwhile, the phase 3 EPCORE FL-2 study is investigating epcoritamab in combination with rituximab and lenalidomide in previously untreated follicular lymphoma, comparing the regimen with chemoimmunotherapy. The ambition is therefore shifting. Researchers are not only asking whether bispecific antibodies can provide another option after multiple treatments have failed; they are asking whether these therapies can be introduced earlier, potentially changing the sequence of treatment itself. The evolution of epcoritamab illustrates one of the fundamental purposes of clinical trials. A treatment can begin as an experimental option available to a relatively small group of patients, accumulate evidence through successive studies and, if the evidence supports it, eventually become part of routine care. And epcoritamab is not alone. Roche’s mosunetuzumab, another CD20 x CD3 T cell-engaging bispecific antibody, is also being investigated across follicular lymphoma. First approved in the U.S. for the indication in December 2022, the drug is being studied further, with a currently recruiting phase 3 study comparing mosunetuzumab to rituximab in people with low-tumor-burden follicular lymphoma, while other studies are exploring combinations with additional agents. Researchers are also beginning to look beyond CD20. Brown himself has already started thinking about what could come after epcoritamab. He talked about AstraZeneca’s investigational drug surovatamig, a CD19 x CD3 bispecific antibody, as a possible future option because it targets a different antigen from epcoritamab; a distinction that matters greatly, because repeatedly targeting the same antigen may not always be the best strategy, particularly as treatment can alter the population of cells carrying that target. Surovatamig is currently being studied in the phase 2 SOUNDTRACK-B trial in people with relapsed or refractory B-cell non-Hodgkin lymphoma, including follicular lymphoma. The drug is designed to engage CD19 on B cells and CD3 on T cells, using the same broad principle as epcoritamab but directing the immune response toward a different target. Early phase 1 data have shown activity in heavily pretreated follicular lymphoma, while the phase 2 study is designed to investigate its efficacy and safety more fully. For Brown, that next generation of therapies is important because he does not see his treatment journey as finished, and he is convinced that bispecifics will have a huge impact on lymphoma treatment in the future. “I mean, look, I’m not a scientist, so I don’t know,” he said. “But I think immunotherapy has to be the answer to this. What you really need to do, ultimately, to my mind, is you’ve got to find a way of making your body destroy those cancer cells.” Bispecific antibodies are one way researchers are trying to do precisely that. CAR-T cell therapy, meanwhile, is a modality that takes this idea further. Rather than giving a ready-made antibody, clinicians collect a patient’s T cells, genetically modify them outside the body so that they recognize cancer cells, multiply the engineered cells, and then return them to the patient. The approach has been groundbreaking for blood cancers and has already become an important treatment strategy for some forms of relapsed lymphoma, but it is a more complex and personalized process than an off-the-shelf bispecific antibody. That distinction is part of what makes bispecific antibodies attractive. They can potentially be manufactured and administered more like conventional medicines, without the individualized cell-manufacturing process required for CAR-T. Nevertheless, when asked whether he would consider a CAR-T trial in the future, Brown’s response was clear: “Yes, absolutely, definitely.” The research landscape continues to expand, with trials exploring combinations of immunotherapies, different targets, and earlier use of these approaches. But for patients, the growing number of possibilities also creates a different challenge: knowing which option might be relevant, and when. Brown believes he waited too long before looking at clinical trials. “Look at trials early if you’ve got follicular,” he said. “Because, if I could have tried it when I was given R², I might have gone on a trial on a bispecific then.” He now encourages other patients to investigate what is available before they reach the point at which their options become limited. “That’s why you should learn about your disease if you feel you can, or get your family to do it,” he stressed. “But it’s just so complicated. You know, there’s so much to learn about when you’ve got something like follicular lymphoma. It’s just incredible. And yet, your life depends on it, because otherwise you’re just taking a doctor’s word for what’s the next best thing to do.” Living with the unknown For all the promise of new therapies, Brown’s life is not measured by clinical-trial endpoints. It is measured in journeys to Manchester, years of work lost, plans disrupted, and ordinary moments that might otherwise have been taken for granted. Because he is self-employed, periods when he cannot work mean periods when he does not earn. He and his wife were fortunate enough to be able to sell their house and move to Yorkshire, eventually becoming mortgage-free. “I’ve lost years of work; but we’ll be okay, we’ll get through it,” he said. “But it’s tough then when you see your friends all retiring, going on regular holidays, and just doing lots of nice things; that was really tough for my wife, you know, everybody else having a fun time and we’ve got a very, very different situation. But I’m alive… It’s just how you look at it, isn’t it?” For now, he works on his house, tackling projects that give him something else to think about. He recently became a grandfather. “That’s the most fantastic thing,” he said. “You’ve just got to focus on all the joy.” Yet living with relapsed lymphoma means that certainty is difficult to come by. Brown has regular check-ups, but the reassurance of one scan does not guarantee what will happen months later. “Relapses never occur on the day you go for your check-up. So, you’re just sort of sitting trying to get on with your life not thinking about it because you can only guarantee that things are going to be okay for probably about two or three months; beyond that, you can’t guarantee anything.” That uncertainty is perhaps the hardest part of a disease that can be controlled repeatedly without necessarily being cured. And yet Brown remains optimistic – something he describes as “a genetic thing”. Even so, he acknowledges that living with cancer can challenge that optimism in “every cell” of the body. “The thing is, you’re tougher than you think you are,” he tells people who imagine they would struggle to cope with a diagnosis like his. “And you kind of don’t know until you are in that situation and adjust to it. You don’t know how you’re going to be. You might find out that you’re tougher than you think you are.” He does not pretend that another relapse is impossible. In fact, he knows that eventually another treatment may be needed. If that happens, he expects to return to The Christie and see what trials are available at that point. “I can’t ever plan ahead,” he said. “You can’t say this is what I’ll do next time because it’s only when you get to that point that it’s worth deciding, because, at that point, there might be other trials available.” For someone who has spent 11 years moving from one treatment to the next, the new normal is that the future is always uncertain. But it is also different from the future he might once have imagined. New treatments are moving from laboratories into clinical trials, from trials into regulatory review, and from regulatory review into routine care. Epcoritamab’s journey from an experimental treatment to an NHS option is one example. Other bispecific antibodies, CAR-T approaches, and new immune targets are now being tested in patients at different stages of disease. To Brown, that scientific progress is not an abstract measure of innovation. It is the possibility of another treatment when the current one stops working. Another remission. Another few years. Perhaps, eventually, another decade. “I just don’t think it’s going to get me.” He pauses. “Which isn’t right. Because it obviously can. And one day probably will. But I just don’t think it is, do you know what I mean? It’s almost like it isn’t happening to me.” For now, that is enough. 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