Rituximab - a game changer -podcast transcript

Date: 7 March 2025

Voiceover (with music playing in background): The Lymphoma Voices podcast brings you a series of conversations around topics of interest for people affected by lymphoma, the fifth most common cancer in the UK.

Anne Hook: Hello, my name is Anne Hook and I'm the Publications Manager at Lymphoma Action. I'm delighted to be joined today by Dr Rob Lown, who is a Consultant Haematologist at the University Hospital Southampton. Hello Rob.

Dr Rob Lown: Hi Anne.

Anne Hook: We're going to talk today about rituximab, but before we do so Rob, I wondered if you could give me just an overview of your role?

Dr Rob Lown: Yes, of course. So I'm a haematology consultant and I specialise largely just in lymphoma nowadays. And I look after patients with lymphoma right from the point of diagnosis all the way through treatment and then follow up in the longer term. That involves treating patients with drugs such as rituximab, but also chemotherapy. And I also look after patients having more intensive treatments such as stem cell transplants and also CAR T cells.

Anne Hook:  So going back to rituximab, if we can focus on that and if we can start by thinking ‘what is rituximab’?

Dr Rob Lown: So, I think the way to think about rituximab is through the body's immune system, because we all have antibodies in our blood, and what are antibodies? Antibodies are substances that our immune system produce when they encounter an infection. And the idea is that these antibodies remember a particular infection and that they remain in the bloodstream for many years.

When they encounter that infection, they can target it and encourage the rest of the immune system to kill that infection off, before somebody becomes unwell.

And what scientists have done is basically copied this process and they've created antibodies in a lab, which rather than target infection, target diseases such as lymphoma. And we don't just use antibodies in lymphoma, we use them in other blood cancers and other cancers that are not in the blood.

And rituximab is antibody like that: it's created in a lab and it's called a monoclonal antibody, and it targets a receptor or a marker on the surface of lymphoma cells. And it binds to these cells and it basically acts as a flag which encourages the rest of the immune systems to come in and kill off those lymphoma cells. And it's proven a remarkably effective treatment for lymphoma, over the years.

Anne Hook: And who is likely to receive rituximab as part of their treatment?

Dr Rob Lown: So rituximab is used in many B cell lymphomas and specifically it's B cell lymphomas rather than T cell lymphomas. And we use it in both high-grade or aggressive B cell lymphomas and also low-grade or indolent B cell lymphomas. And these all come under the umbrella with non-Hodgkin lymphoma. So almost all non-Hodgkin lymphomas have rituximab as part of their treatment at some point.

Anne Hook: Can you give us some examples of the most common B cell lymphomas?

Dr Rob Lown: Yes. So I always split these into the fast-growing aggressive lymphomas and the slow-growing low-grade lymphomas and I'll start with the latter.

So of the slow-growing low-grade lymphomas, most commonly we see follicular lymphoma’s by far and away the most common slow-growing lymphoma and then less commonly marginal zone lymphoma and also a disease called Lymphoplasmacytic lymphoma, some people know this more commonly as Waldenström's macroglobulinemia.

And then the high-grade lymphomas, most commonly diffuse large B cell lymphoma. And then we see other lymphomas such as mantle cell lymphoma and Burkitt lymphoma, which are much less common.

Anne Hook: We've heard from some people that they have only rituximab as part of their treatment. You know, they might have four rounds of rituximab and that's it. But for the vast majority they have it as part of a chemotherapy regimen. Can you explain the difference and why you may take one approach over the other?

Dr Rob Lown: There are probably two common situations where we use rituximab on its own rather than in combination with chemotherapy treatment. And I would say the first one and probably more commonly is in a condition called marginal zone lymphoma. This is a slow-growing non-Hodgkin lymphoma that often only needs fairly gentle treatment with rituximab to either stop it progressing or – ideally – put it back into remission. And patients typically receive rituximab once a week for anywhere between four to eight weeks for this type of lymphoma.

The other condition where we do use it is in follicular lymphoma and typically this is in patients who have relatively few symptoms from their lymphoma. But for various reasons, we don't feel that an expectant management or active monitoring (what we used to call watch and wait approach) is appropriate, and this may be because the physician is not comfortable or because the patient is not comfortable. And giving rituximab on its own in this situation can delay the time for patients to need chemotherapy treatment.

Anne Hook: So somebody who, for example, was being given R-CHOP chemotherapy that we've got the rituximab at the front of that. I've heard in the past it being said that rituximab was quite a game changer. Is that your opinion as well?

Dr Rob Lown: Absolutely. You know, for many years, CHOP on its own was the best treatment for aggressive lymphomas, particularly diffuse large B-cell lymphomas. And many people tried to see if we could make it better by adding in more chemotherapy drugs and all that did was give people more side effects without increasing the chance of patients being put into remission or potentially cured. And so along came rituximab and suddenly we had a new drug that we could add to CHOP, which made a really big difference in terms of remission rates and also long-term remission and long-term survival for patients.

So, particularly in aggressive lymphomas but also more recently in slow growing lymphomas, it has really changed the outcome for these patients.

Anne Hook: So can I ask you, is there a difference between the rituximab that's given as part of a chemotherapy regimen, to that that's given as maintenance at the end of treatment?

Dr Rob Lown: Yeah, it's a good question. The drug essentially is the same, it has the same action. The main difference between having rituximab as part of a chemotherapy regimen and having it as maintenance, is that usually when you're having it with chemotherapy it's given through the vein like many of the other chemotherapy drugs. However, for maintenance, it's often given subcutaneously, which means it's an injection under the skin.

But the drug itself is the same, it's just the way it's given is different usually between chemotherapy treatment and maintenance.

Anne Hook: And are they always done in hospital as an outpatient, or typically as an outpatient?

Dr Rob Lown: It very much depends on the hospital. I can speak from our own experience at Southampton: for maintenance treatment we can give them on our chemotherapy unit, but we also have a home care service where nurses can actually come to the patient's home and give the rituximab in the comfort of your own armchair.

Anne Hook: Can I ask, does rituximab have any side effects?

Dr Rob Lown: Yes, it does and I often when I'm talking to patients about rituximab, I break it down into the early immediate side effects and then the longer-term side effects.

So, you know, we've talked about it being better tolerated than chemotherapy, but the one thing I would say is when patients have the first dose of rituximab, there's always a risk of a reaction and what we call an ‘infusion reaction’. That can mean having a temperature, feeling light-headed, feeling clammy, sometimes feeling tight on the chest or short of breath. And it's usually managed simply by slowing the infusion down, giving medications such as antihistamines and paracetamol and generally it doesn't stop the patient receiving the full dose of the drug.

Sometimes we do have to abandon it and have another go later but usually by the second dose of rituximab, those infusion reactions are much less or don't happen at all. And generally from the third cycle on, actually there's very few infusion reactions. So that is the main early reaction to rituximab.

The other, later-effects is based on the effects of rituximab on the body's immune system, because whilst these drugs are very good at targeting B cell lymphomas, what they also do is target normal B cells as well. These are essential parts of your immune system. And so in the longer term it can suppress the immune system and make you more vulnerable to infections, particularly virus-type infections, but sometimes other infections such as chest infections and urine infections.

Generally we will discuss this with the patients and we always think about the risk of infection in the longer term, particularly when it comes to maintenance treatment.

Anne Hook: And how long is somebody likely to be on maintenance rituximab?

Dr Rob Lown: So most commonly it's for two years. So patients have the maintenance treatment usually every eight weeks or so for two years, so 12 doses in total. In some cases your doctor may actually recommend that people stay on it for longer, but generally two years.

Anne Hook: And we've talked about the short-term side effects and the immune system, are there any long-term side effects people should be aware of?

Dr Rob Lown: So infection really is the main one in the longer term and it's quite a big decision to go on maintenance rituximab because there is a risk in the longer term that people can start to suffer from recurrent infections. And the important thing is that before starting, you have a discussion with your doctor about the infection risk and the doctor will consider not just the lymphoma, but also, you know, do you have a history of chest infections, have you been a heavy smoker, things like that, which can impact on the risk of infections.

And then the important thing as you go through the treatment, if you start maintenance, is that that discussion continues to happen as you go through. And we do have patients who maybe are four to five doses into maintenance that are starting to get recurrent infections. And usually for us, you know, that is an absolute need to stop the treatment because the risk of infections then is starting to outweigh the benefits that people may get from rituximab.

Anne Hook: And callers to the helpline often worry that going on maintenance rituximab is going to be as gruelling as the whole chemotherapy experience was earlier. Do you have any words of reassurance on that?

Dr Rob Lown: I think for the majority of patients that's not the case. Chemotherapy treatment is usually tougher than rituximab maintenance. My general experience, and of course there will be exceptions, but my general experience is when people are on maintenance treatment, as long as they're not getting infections, the main side effect is feeling a bit sleepy for a day or so after the rituximab injection. There may be a little bit of soreness on the tummy for a day or so after the injection, but then usually life carries on as normal after that until the next dose.

Anne Hook: And you've said that people can be on it for as long as two years. Does the effect of it diminish over time?

Dr Rob Lown: That's a really good question. You know, there's always a possibility that lymphomas can become resistant to rituximab. We don't routinely check for that.

In some patients, rituximab will stop working, we do see that and sometimes we see people whose lymphoma comes back whilst they're on maintenance rituximab treatment.

However, we don't really have a reliable way of predicting who those people will be.

Anne Hook: And if it does return, there are other treatments, presumably other chemotherapy regimens that can be introduced.

Dr Rob Lown: Yes, there will be for most patients with lymphoma we would, you know, we have several options now for treating different types of lymphoma.

Anne Hook: The other thing we hear about is biosimilars. Can you explain what biosimilars are, Rob? And also, should anyone be worried if they're being offered a biosimilar rather than the branded rituximab?

Dr Rob Lown: So, what are biosimilars? So, with any drug, the drug company that produces them puts a lot of money into researching these drugs, developing the drugs and bringing them into practise so patients can benefit from them. And usually those drug companies have a patent which will cover that drug for, you know, maybe 20-25 years before another company can make it. And when those patents run out, other drug companies can make these drugs: they're called generic drugs. And biosimilars really are the same thing.

They are essentially made from in the same way as the original drug. They provide the same benefits when treating lymphoma, for example, they're given at the same strength and dosage and they have the same side effects as the original drug.

And any regulatory authority – in the UK it's called the MHRA – will make sure that these biosimilar drugs meet those requirements. So in a nutshell biosimilars are the same drug and they have the same effect. The main difference really from a healthcare-provision point of view is that they're more affordable.

Anne Hook: As a reminder, the original rituximab was called MabThera. Is that right?

Dr Rob Lown: Yes, that’s right. Yeah. So interestingly, in lymphoma, most places we use biosimilar rituximab for intravenous treatments with chemotherapy. But subcutaneous rituximab is still under patent and most of us use original MabThera for subcutaneous maintenance treatment.

Anne Hook: Rob, can I ask you, you've mentioned that if people need treatment again, there's quite a few options available. But will they include rituximab in any future treatments if people have already had it and maybe even had maintenance for a period of time?

Dr Rob Lown: The short answer is yes. We often use rituximab in what we call second-line and third-line. So these are the next line of treatment for your lymphoma.

We do usually do biopsies if patient’s lymphoma comes back and we can check actually for the target for rituximab on those biopsies. And in patients where we don't see that target because it's been lost – and this is a way that the lymphoma can become resistant to rituximab - if that's been lost, then often we won't offer rituximab again. But if it's still there, then most of our regimens will include rituximab as part of that treatment. You know, your doctor will be able to discuss this with you at the time.

Anne Hook: And is there any place for scans or testing to see how effective rituximab is at all?

Dr Rob Lown: Yes. We, of course, do scans when we're using rituximab in combination with chemotherapy. And then usually during maintenance treatment, my own personal practise is I'll do a scan after one year, and then again at the end of maintenance treatment, particularly for lymphomas like follicular lymphoma. And this is – at least in part – to make sure that it's worth continuing with the rituximab maintenance at that point.

Anne Hook: So that scan will show whether the lymphoma is staying stable.

Dr Rob Lown: Yeah.

Anne Hook: Could it be shrinking with the maintenance?

Dr Rob Lown: It could be, yeah we do see that. We see people where we finish the chemotherapy and there still are some enlarged lymph nodes either on a CT scan or a PET scan. And sometimes when we do these follow-up scans on maintenance, we see the lymph nodes shrinking down.

Anne Hook: I also wanted to ask you about vaccinations. I know one of the big worries is this risk of infection. There's the shingles vaccination, there's flu jabs, there's COVID vaccines. What's your view on all those things?

Dr Rob Lown: So, I will recommend to my patients, particularly if they're on rituximab maintenance or indeed they've had rituximab in the past, I would recommend that they take up the vaccines that are offered to them. So currently this is a twice-yearly COVID vaccine and then certainly the seasonal influenza flu vaccine when that comes up. So I’ll routinely recommend that to my patients.

And I do think it's an important way for patients to be able to manage the risk of infection. Because whilst patients are on maintenance rituximab, you know, the chemotherapy part, the hard part of the treatment is finished and we like to try and encourage people to go out and live as normal a life as possible at that point, and vaccination is one way that patients can remain safer in doing that.

Anne Hook: And I mentioned the shingles vaccine, but I'm very mindful people shouldn't have it if it's the live vaccine, but there is one now that is not the live vaccine.

Dr Rob Lown: There is one a non-live vaccine available to certain age group, which if patients are offered it, I'm very happy for them to receive that vaccine.

Anne Hook: You mentioned about precautions for a long period of time and it's very difficult for people. We hear on the helpline that, you know, there's not an end to treatment. You know, people have said, ‘oh, you've got to the end of treatment’ but actually it's going on and on for two years. What would your thoughts be to people on that predicament?

Dr Rob Lown: Do you know it's so… it varies from person to person and some people just want to be finished with the treatment. And in most cases, maintenance is optional, you know, we certainly don't tell patients you absolutely have to have this. And some people just want to be finished, they just want to get on with life and not have to come back every two months for the treatment. And in most cases that's a reasonable thing: we'll talk through the benefits and the risks of maintenance and some patients will make that decision.

For other patients, they absolutely will want to do everything they possibly can to reduce the risk of their lymphoma coming back or improving the remission of their lymphoma. So for them, going on maintenance is a much easier decision.

I always try and encourage people after they finish chemotherapy treatment that they can relax some of those precautions they're taking in terms of diet, in terms of social contact, because the risk of serious infection is much less once you're on maintenance treatment. But again, people will have different discussions with their doctor and I think the important thing is that there's no one-size-fits-all approach. It's all about having that discussion with your physician, talking about in the context of your own lymphoma, perhaps your other medical problems.

Anne Hook: There is a newer drug and it's a sort of version of rituximab called Obinutuzumab. Can you tell us a bit more about that?

Dr Rob Lown: Yes. So, obinutuzumab is an antibody, monoclonal antibody just like rituximab and it also has the same target as rituximab. But at least in the lab, the obinutuzumab seems to be better at encouraging the immune system to attack lymphoma cells. And in some trials it does appear to be slightly better, so patients with follicular lymphoma may be offered obinutuzumab rather than rituximab as part of their treatment.

Whereas in high-grade lymphoma such as diffuse large B-cell lymphoma, it wasn't shown to have any benefits at all, so those patients will still have rituximab. But it is used in combination with chemotherapy in a very similar way and it also can be used as maintenance treatment in a very similar way to rituximab in the longer term.

Anne Hook: Rob, I have got an additional question, I hope you don't mind. And that is, what motivates you to do your job?

Dr Rob Lown: Ah, several things. As an oncologist, it is a huge pleasure and a huge honour to be able to diagnose patients with an illness, see them all the way through the pathway to the point of being able to give good news at the end of it, which I'm pleased to say we do for most patients. And to develop those relationships, that it's almost unique I think, because we really do see people right from the very beginning and develop relationships with the patients, with their relatives, all the way through that treatment pathway.

I can honestly say hand on heart, that is what gets me out of bed in the morning and gets me into work.

But, I also love working with my team. I have a fabulous team. I say ‘I have’ we, you know, we are a very democratic team at Southampton, we all share responsibility for the service that we deliver. I’ve a fabulous consultant and junior doctor colleagues, a brilliant nurse specialist team in lymphoma, but also a fabulous specialist team in our transplant unit and the CAR-T unit as well.

So it's a combination of those two things I think, that really, really keep me going at work.

Anne Hook: Rob, thank you so much for your time today and for sharing your thoughts on rituximab. We'd really appreciate it.

Dr Rob Lown: You're very welcome.

Voiceover (with music playing in background): For more information about lymphoma and the support we can offer to people affected by the condition, please visit the Lymphoma Action website at www.lymphoma-action.org.uk 

Lymphoma Action: inform, support, connect.

Total time: 21 minutes

Disclaimer

This transcription has been automatically generated. However, Lymphoma Action has taken all reasonable steps to check its accuracy. The content is not intended to be medical advice. If you are looking for specific medical advice for your own personal circumstances always consult your medical team.