Laurie Sehn, MD 

Having set this landscape with the pending availability, at least in the United States and, hopefully, Canada, of the bispecific antibody mosunetuzumab, then you have to ask the question, in a world where we have access to both CAR [chimeric antigen receptor T-cell therapy] and mosunetuzumab in the treatment of FL [follicular lymphoma], for me, the value proposition of bispecifics in follicular lymphoma is different than they are in large-cell lymphoma because of that question of cure that you so importantly invoked. We know that CAR T-cell therapies hold curative potential in the treatment of diffused large B-cell lymphoma. It’s not yet so clear that that is true, or if it is true, that it may not also be true with bispecifics. So when you’re dealing with treatments that don’t have that same ethical burden of offering treatment with curative potential and prioritizing it, for me, it allows a prioritization of bispecific antibodies with a preferred toxicity profile and outpatient management, easier access. We’re reserving the more toxic CAR T-cell therapy for patients who don’t respond adequately or relapse subsequently following bispecific antibody treatment.

I would fully agree. Clearly, we don’t have comparative data that compares them side by side to tell us which is preferred. I think what we’d love to learn is which patients, based on their unique biology, would preferentially benefit from a bispecific vs CAR T-cell therapy and how to sequence these 2 different approaches in individual patients. We’re not there yet, but it would be nice to think that with evolving biological insight, we might one day get a point where we can pick strategies based on biology.

In the absence of having that ability, we’re left weighing the 2 strategies based on what we understand their efficacy to be measured against their toxicities, resource intensity, inconvenience, and cost. And I would agree that right now, based on the weight of the data, it’s most likely that bispecific antibodies will jump ahead of CAR T-cell therapy for most patients because of the preferential ease of administration, toxicity profiles, and, at least for the time being, [a] lower risk of longer-term toxicities. It’ll be fascinating as we see the longer-term data from both CAR T-cell therapy and the bispecifics and understand more about the durability of benefit or the potential for curability. That would clearly sway where they may be weighted. But, for the time being, I think bispecifics will come out as preferentially utilized ahead of CAR T-cell therapy.

There’s clearly a lot we have left to learn about bispecifics and how best to leverage them in the treatment of our patients with follicular lymphoma, not just in terms of understanding the long-term properties of monotherapy, but also in what line of therapy [they’re] best deployed in, whether there are appropriate partners for building combination treatment programs to offer improved disease control. Are there ongoing studies that particularly have you excited for the future development of this class of drug?

Yes. Inevitably, we’re all excited based on the activity we’re seeing in the third-line setting and beyond, [thinking] about what drugs like the bispecifics [might] do in an earlier setting. We’ve got registration trials that are being planned in the second-line setting that are going to be randomized trials in which they’re combined with lenalidomide. For example, mosunetuzumab and lenalidomide is going to be compared against R2 (lenalidomide, rituximab) to see where it lines up. I think that given the modality of action of bispecifics, that it’s a type of immunotherapy, the idea of combining it with other immunotherapy approaches that might augment that modality is really enticing. This combination of mosunetuzumab and lenalidomide is shown to be quite effective in a phase 2 study that was reported, so it’s exciting to see that that’s going to be moving to a randomized comparison in the second-line setting. But there are many trials across the board looking at combinations of bispecifics with a variety of novel therapies in development. I think this makes for a very exciting time to figure out how we can leverage some of these very promising treatments by combining them with either existing treatments or other novel treatments that will either synergize or make the efficacy better across the board.

I really agree with you about the attractiveness of lenalidomide as a partner for these agents. We’re soon opening a multicenter study looking at mosunetuzumab in combination with lenalidomide and the anti-CD19 drug tafasitamab. Tafasitamab plus lenalidomide has been an approved combination treatment for relapsed, diffused large B-cell lymphoma. So we’re looking at this as a potential triplet in both aggressive and indolent lymphomas to see whether you can leverage that combination treatment further. You can’t co-administer CD20 antibodies like rituximab with mosunetuzumab because [of binding issues], but administering a CD19 antibody is feasible. We’ll see whether that triplet offers any additional promise. I’m also excited to see the first-line data for mosunetuzumab monotherapy. The idea that this class of drugs is active and well-tolerated enough to potentially supplant the standard immunotherapy approach for patients with newly diagnosed follicular lymphoma is very exciting.

Absolutely, and it’ll be probably some time before we see that data emerge. Until then, we are seeing data from single-arm trials of monotherapy with bispecifics, and this makes a very attractive alternative for the elderly or frail patient where chemoimmunotherapy has never been a particular attractive option. So I certainly look forward to more data emerging in that patient population and how these new options might be an alternative to what we currently have to offer.

Dr Sehn, you’ve painted a picture for us in the field of follicular lymphoma where we have established standards of care in the first-line setting despite this being a remarkably heterogenous disease. As patients experience subsequent relapses, that heterogeneity further complicates clinical decision-making. Despite that, we have a growing armamentarium of options both currently approved as well as emerging therapies, such as bispecific antibodies, that hopefully offer our patients more hope and give us as oncologists more options to individualize and personalize the care of our patients. So I share your enthusiasm and thank you for sharing your perspective and wisdom with us this evening.

Thank you. I think it’s a remarkably exciting time. This is one of many conversations I’m sure we’ll be having because there’s a lot of data emerging and treatment is changing, treatment options are increasing. It’s certainly adding to the complexity but also to the excitement, and certainly we expect that outcomes will be improving as well.

Well put. Thank you to our audience for watching this 

 discussion. We hope that you found this discussion informative and valuable in the treatment of your patients with follicular lymphoma.

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Closing out their discussion on bispecific antibody therapies, Matthew Matasar, MD and Laurie Sehn, MD, consider ongoing clinical trials and real-world use of these novel agents.

Follicular Lymphoma: Forecasting Bispecific Antibody Treatment Strategies

The point you make is a good one about sort of looking at the nuance of how these drugs are being developed. And there are differences between and among these agents, both in terms of, is it finite therapy, such as mosunetuzumab and glofitamab, or extended therapy, such as epcoritamab and odronextamab treatment until progression or intolerance with those. Some are given intravenously and some subcutaneously. But for me, one of the most important differences is the differences in the toxicity profile of these agents, particularly in the context of follicular lymphoma where toxicity considerations may become even more important than they might be in the measure of aggressive lymphomas. I’d love to hear your take on the toxicity of mosunetuzumab and how you’ve experienced that in using this in the ongoing trials.

The bispecific antibodies targeting CD20 and CD3 come with a unique set of toxicities that will present a learning curve for clinicians who haven’t used them. We’ll all need to develop strategies to anticipate these toxicities and to manage them. I suspect as these drugs roll out and gain approval that there’ll be clear-cut management guidelines for each of the individual drugs based on what was seen in the clinical trials, guiding clinicians as to how to manage the initial introduction of the drugs. So the toxicities I’m referring to are [from] cytokine release syndrome [CRS]…[which is] probably the main unique toxicity that will need to be taken into account.

The important thing to realize is many of us started to understand what cytokine release syndrome was based on our experience from CAR [chimeric antigen receptor] T-cell therapy, where it was similarly a relevant toxicity. I think there’s been a big learning curve in the management of CAR T-cell therapy patients to better understand the management of CRS in the bispecific antibody setting, but for the most part, across the board in clinical trials with the bispecific agents, the CRS that we’re seeing is largely low grade in nature; grade 1 or 2, and it typically will occur in the first cycle.

To ameliorate that and to reduce the risk of very pronounced cytokine release syndrome, most of the drugs have introduced step-up dosing in the first cycle. Patients get many doses in the first couple of weeks. An initial loading dose in the phase 1 component of these trials has shown to lower the risk of cytokine release syndrome and lower the grade of cytokine release syndrome. In some of these trials, some patients have needed steroids or tocilizumab. In some cases, the steroids are given preemptively. But, in general, it is a fairly manageable toxicity with a very low likelihood of patients developing high-grade toxicity. However, this is a toxicity that clinicians will need to anticipate, need to manage, either preemptively or reactively, and also will need to have strategies to take care of the rarer patients who do develop more significant CRS.

I think, ultimately, we expect that most of these agents will come out as outpatient treatment. So they’ve fine-tuned the scheduling in these early trials, particularly for the subcutaneous agents that probably has reduced the risk of very significant CRS, allowing them to be given in the outpatient setting. But I think [there will] be a learning curve. We’ll all have to develop management strategies and make sure that we can deliver them safely. But keep in mind this is a cycle 1 problem. Beyond generally cycle 1 and rarely cycle 2, the risk of CRS is virtually nonexistent, and patients tolerate it very well after that.

The other toxicity we’ve learned about from CAR T-cell therapy has been the neurologic toxicities that we can see with immunotherapies—often referred to as ICANs [immune effector cell-associated neurotoxicity syndrome] when we refer to it in a CAR T-cell setting. I would say that that risk with bispecifics is exceedingly low. So while some element of neurologic toxicity has been reported, I think that based on how neurotoxicity is captured in clinical trials, or [potentially] attributing some neurotoxicity or other complications to…the drug, in my experience, it has been a really low risk with bispecifics, and I think it is not going to present a huge impediment for outpatient management. Then the other main toxicity that we see is cytopenias, which is quite comparable, but less than we see with chemotherapies, and I think most clinicians are comfortable managing cytopenias.

For me, it really comes down to CRS management. It is, as you’ve said, particularly with mosunetuzumab, relatively low rates and relatively low grade, but grade 2 CRS is still something that requires medical intervention. This is being developed as a fully outpatient therapy, which is key to being able to deploy it, to offer broader access, and in order to [educate] oncologists, nurses, emergency departments, and hospitalists on how to recognize and diagnose CRS. [It’s also educating about] how to distinguish it from infusion-related reactions, and when and how to intervene. So there’s a lot of work that’s going to have to underlie the clinical rollout of these agents to support their safe administration and broad context.

Absolutely. I think you make a really important point that it’s not just education among the oncologists. These will become mainstream drugs. CAR T-cell therapy is still relegated to specialty centers where many patients are treated as inpatients, and these toxicities have rolled out while they’re under the care of a specialist. Whereas, I think we’ll inevitably see bispecifics roll out into the community, and many other complications will make their way into local emergency departments. It’ll be a big learning curve across the medical environment that needs to take place to make sure these patients are managed safely. But I’m quite confident that this is doable with these agents based on the degree of toxicities we’re seeing. Most of the toxicities can be quite predictable in terms of timing, and with the right strategies in place, I think that these will be amendable to outpatient care.

Again, there are differences among the bispecific antibodies, where mosunetuzumab seems to have the lowest rates of cytokine release and other severe adverse events. Very low rate to treatment interruption, discontinuation in the pivotal study. Whereas glofitamab/epcoritamab may be more potent, particularly in the treatment of aggressive B-cell lymphomas, but associated at higher rates of cytokine release syndrome of grade 2 or greater. It may be more challenging to administer in general practice.

It’s hard sometimes to compare across these trials…but I do agree in general. For example, with glofitamab, which has been tested in both follicular lymphoma and aggressive B-cell lymphomas, there is a slightly higher risk of CRS. So, whether it’s a more indolent [disease]—like follicular lymphoma, where the data looks very good for efficacy with alternative agents like mosunetuzumab—whether or not that will become the preferred agent because of its maybe more favorable toxicity profile, I think that we will see some selection of the bispecifics geared toward individual patients based on this comparative toxicity that we, at least at the present, perceive. But I think we don’t want to make too much in the way of overstatements because at this point it’s still the separate trials with separate groups of patients and it’s probably hard to really make the comparison.

Experts Matthew Matasar, MD and Laurie Sehn, MD, nuance the adverse event profiles of bispecific antibody therapies and consider how these will help inform treatment decisionmaking.

Bispecific Antibodies in Relapsed/Refractory Follicular Lymphoma: AE Management

Expert perspectives on the advent of bispecific antibody therapy in relapsed/refractory follicular lymphoma, centered on data and experience with several novel agents.

Advent of Bispecific Antibodies for Relapsed/Refractory Follicular Lymphoma 

I guess the opposite end of the spectrum from tazemetostat with modest activity but extraordinary tolerability would be CAR [chimeric antigen receptor] T-cell therapy, which is a treatment with a well-characterized and significant toxicity profile with tremendous activity, even in patients with multiple relapses and at high risk for follicular lymphoma. What’s your current approach to CAR T-cell therapy? In which patients is this a preferred treatment approach, in your opinion?

I think it’s not a surprise to any of us that a disease like follicular lymphoma would be amenable to treatment with an immunotherapy approach such as CAR T-cell therapy. The data is probably not surprising to anybody that this is a modality of treatment that may be valuable for this indolent lymphoma, where we know that immunotherapy can be very powerful. The problem with CAR T-cell therapy, in my mind, is that it is still more of a big-gun treatment. It’s cellular therapy, but we know that it comes with real potential toxicities for patients, both in terms of acute risks such as neurologic toxicity and cytokine release syndrome, and delayed toxicities with prolonged cytopenias. With a disease that is a marathon and requires treating patients over the course of their lifetimes, at what point do you bring in CAR T-cell therapy? The answer is a little unclear.

It’s also a capitated resource in many places. It’s a growing field of importance for lymphoma, certainly. In my own clinic...we have limited access to CAR T-cell therapy for follicular lymphoma because we’re still trying to grapple with the resources, needing to provide it for all patients with more aggressive lymphomas that were shown to be potentially curative. I would say that currently, the data obviously supports CAR T-cell therapy being a potentially valuable treatment option for patients with follicular lymphoma in the third-line setting or beyond. But not all patients are equal in the relapsed/refractory setting. We’ve got many patients who have delayed relapses—their last treatment was 7 years ago, and they need to go on to the next treatment. Just because there’s a third line, it doesn’t mean I’m out of options. We reuse therapies all the time in patients with follicular lymphoma.

With all my patients, I ask myself, what have they received already? How have they benefited from what they’ve received? How long have they benefited? How did they tolerate it? And then [I review] all the options I have, and certainly reusing options that have been used before can be a consideration. How does that weigh against CAR T-cell therapy, resource intensity, and the expense? But a more concerning consideration would be, is this going to close the door down the road for any other treatments for these patients? If a patient develops prolonged cytopenias from CAR T-cell therapy can I come in with another drug down the road? I might now be prohibited from giving it. So I think tThere are some concerns around CAR T-cell therapy regarding its expense and toxicities where I probably would have look at a patient to [determine where I’ll] need to bring in this modality vs use some of the other options that might be less intensive, and save CAR T-cell therapy for further down the line.

I’d really love to hear what you have to say in terms of what you do in your own clinic because the data is still very early regarding the use of CAR T-cell therapy for follicular lymphoma. Despite the extended course of the disease, we still have only short-term follow-up. With longer follow-up, if we find that we’re able to cure some of our patients with follicular lymphoma, I think CAR T-cell therapy is a total game changer. But right now, it’s just another therapy that has the capacity to control the disease for a period of time. Thus it entails a risk-benefit vs an expense-resource balance.

I completely agree. The data are attractive; it’s clearly potent. But it’s the minority of patients who require that big gun. Patients who have transformed disease, patients in a highly aggressive fashion, those who have a loss of CD20, rapidly progressive disease, highly refractory disease, patients who need a very quick response or else are at risk of dying from disease, those are the patients who are preferentially shunted toward CAR T-cell therapy. But for me, the broader opportunity of CAR T-cell therapy is the proof of principle. It’s not surprising that follicular lymphoma should respond to T-cell therapies, but I really view it as a proof of principle, and it makes investigations into other immunotherapeutic approaches of follicular lymphoma more attractive.

Shared insight on the development and use of CAR T-cell therapy in patients with multiply relapsed follicular lymphoma.

Multiply Relapsed Follicular Lymphoma: Overview on CAR T-Cell Therapy 

I’d love to hear your take on the emerging and broadening armamentarium for patients with multiple relapsed FL [follicular lymphoma] and how you looked at the currently available agents and any agents that are yet to come.

I think it’s an exciting time. We are starting to see more and more options become available. It also makes it a challenging time because it means that we’ve got more to think about in terms of how to sequence some of these novel agents that are showing benefit for patients with relapsed/refractory follicular lymphoma. PI3-kinase [PI3k] inhibitors have been around for a while now, mainly approved in the third-line setting and beyond. They’ve shown what I would describe as modest activity for relapsed/refractory follicular lymphoma, and therefore remain an option, but what we’ve seen is that the concerns for toxicities have kind of stunted their use across the board. We’ve seen several of them actually come off the market for follicular lymphoma this year because of the [competing drug market], and probably, risk-benefit ratio no longer favoring those agents. We know that copanlisib, for example, is a PI3-kinase inhibitor that is still available, but I do think that that is a drug that, in my mind, has somewhat modest activity and also a difficult schedule for patients. It’s quite frequent treatment, it’s intravenous treatment, it is not a drug that I would routinely use in my own clinic.

Copanlisib is an interesting drug because it doesn’t have the toxicities that have plagued the oral PI3k inhibitors. It’s low rates of hepatitis, enteritis, and pneumonitis. For patients that live close to a center and don’t mind a weekly schedule, it’s a nice agent to offer, particularly if they’re more frail and may not tolerate more intensive treatment approaches. But the schedule really is limiting, and it would be nice to see some data with the agent around intermittent treatment. Either spacing out the therapy or giving treatment holidays to avoid this [3 weeks on 3 weeks off dosing] until progression or intolerance, which can be so challenging for patients.

: I fully agree. I have to say that’s been a problem with PI3-kinase inhibitor development across the board. I don’t feel that, as a class of agents, we need to throw them out. I think we need to better understand how they could be used in a safer fashion. Even the oral drugs that are no longer available or recommended, if we can go back to the drawing board and think about how we might use them at a different dose level, maybe in a combination where they offer synergy but don’t need to be used indefinitely. I think we need to go back to square one for some of those drugs.

Partially this is why I’m excited about zandelisib as a future therapy. Knowing that we have this agent that you get for 2 months in an induction format before you start seeing the emergence of the immune-related adverse events from the tonic T-reg [regulatory T-cell] inhibition, and then you go to a 1-week on 3-weeks off format, showing that you can give that drug in a sustained fashion in this way, without sacrificing disease control, and without incurring the toxicity profile of daily oral administration of PI3Ks. I’m hopeful that future data will affirm the early findings and lead to this becoming a relevant option for patients.

Other agents that have become available, beyond the space of PI3Ks, include the EZH2 inhibitor tazemetostat, which is a definitely unique drug in this disease. I’d love to hear your perspective on how that’s currently being used and how it might be u

Yeah, I think that’s a fascinating drug, because it really is one of the first drugs that we’ve had that is designed to manipulate what we understand to be part of the relevant biology of follicular lymphoma, and that is epigenetic dysregulation. So the EZH2 inhibitors target something that is mutated in only about 20% of patients with follicular lymphoma but is probably clinically relevant in the majority. The intriguing thing about this drug is that it’s easy to administer, and that it’s oral. The other intriguing thing is that the toxicity profile is really low. So it’s a well-tolerated oral drug that does have activity in follicular lymphoma. Although, in the pivotal trial that earned its approval, what we saw is that it was more effective in patients who had EZH2 mutations than in wild-type patients. That, unfortunately, is the minority of patients, probably about 15%-20% only. But in that subgroup of patients with known EZH2 mutations, it can be a very effective option. The response rates are fairly high and we’ve seen durable benefits reported in that patient subset. It’s probably not the drug I would rush to give in a patient who had wild-type EZH2 by testing, but we know that even some of those patients can benefit. I think it’s all a matter of, at that point, what are the other options available to the patient and sort of balancing out that risk-benefit ratio.

It is interesting that even the wild-type patients that respond, it’s a lower overall response rate, clearly, but the patients that respond seem to enjoy a durability of response that’s comparable, or maybe even a little better, to that experienced by the patients who harbor EZH2 mutations. I think this leads me to believe that we don’t really understand exactly what this drug is doing. We don’t have the best biomarkers for predicting response.The flip side of that is the tolerability.

Absolutely, I fully agree with you. There’s probably something that we’re not currently measuring to allow us to identify the patients who will benefit the most or the longest. But, at least at this point in time, given that discrepancy in response rates, I’d probably be more apt to use it in a patient that I know had mutated EZH2 than [one who did] not. I think your point is really well-taken, that patients with wild type EZH2 who benefit do seem to have equally durable benefits, so clearly it’s probably working in a way that we don’t fully understand.

In my practice, tazemetostat is an attractive option for older and frailer patients. These are patients that are not always well-captured in clinical trials, and certainly not always cared for in the context of academic medical centers, but this is a disease that is more common as we age and certainly the burden of FL in older, frailer populations is under-recognized. A drug with a toxicity profile that’s as favorable as that of tazemetostat is an appropriate option for such patients, even in the absence of a mutation, or in the absence of knowing the mutational status.

Absolutely. As you state, this is often a disease of elderly patients, and patients with other comorbidities, and many of the treatments that we have really might be inappropriate for certain patients in our clinic. I think this is where patient preferences come in as well. Beyond suitability, we know that we’ve got patients who have different preferences in terms of the types of treatments that they want. So with this as an option, I think it does become an important discussion with a patient, weighing in expectations of benefit vs the positive aspects of convenience, in that it’s oral, and of course the low toxicity profile. It’s certainly an important addition, I think, to options that patients will need to consider.

Switching to the paradigm of multiply relapsed follicular lymphoma, expert participants discuss the rationale behind and use of PI3k- and EZH2- targeted therapies.

Novel Targeted Agents in Multiply Relapsed Follicular Lymphoma 

Regardless of first-line treatment, whether it’s chemo-immunotherapy, with or without maintenance, or customized monotherapy, these challenges are going to be doubled when you’re trying to manage a patient with relapsed or refractory disease. How do you approach that decision-making? Obviously there’s a lot of nuance that goes into it, including incorporating what the first-line therapy was, what the duration of benefit was, and the relapse pattern. Maybe you could help us understand your approach to a patient with relapsed follicular lymphoma.

That is an area where I would say we really don’t have a current standard of care. I think in the upfront setting, chemo-immunotherapy still would be considered the frontline standard of care. We know that chemotherapy has been around for a long time for follicular lymphoma. We’ve got a number of options such as CHOP [cyclophosphamide, hydroxydaunorubicin, vincristine sulfate, and prednisone] and now bendamustine. What we did learn was that adding a CD20 monoclonal antibody in the upfront setting improved the overall survival for these patients, which, of course, made anti-CD20 and chemotherapy the upfront standard of care. And then, as we talked about, the option to continue the anti-CD20 maintenance for the improvement and progression-free survival.

But beyond that, I think most of us are hoping to see a future where we’re relying more on targeted therapies and nonchemotherapy-based approaches. Unfortunately, in the 1 trial where it looked like we might be replacing chemotherapy on the frontline setting, the RELEVANCE trial, which actually compared R2 [lenalidomide and rituximab] against a chemo-immunotherapy approach upfront, that trial, which was designed to prove superiority of the R2 approach, unfortunately didn’t prove superiority. So it was considered a negative trial and therefore did not come out as an approved treatment in the frontline setting based on the data. But what we clearly learned from that trial was that it was a very effective treatment for patients with follicular lymphoma, and the curves were virtually superimposable. So the results from frontline chemo-immunotherapy vs R2 were quite comparable from the RELEVANCE trial.

As I said, there wasn’t enough from that trial to earn an indication in that setting, and I suppose that if a patient was not a chemotherapy candidate, it would be the alternative that we would want to use upfront. Having said that, in the relapsed/refractory setting I think it’s become probably the most popular choice, based on the data that we’ve seen not only from the RELEVANCE trialupfront, but based on data that’s also been shown in the relapsed/refractory setting. So my tactic for the patient in the second-line setting would be probably to move away from chemo-immunotherapy, and I think R2 is kind of the logical contender in the second-line setting.

The one caveat is that not all patients with relapsed/refractory disease are created equal. We now recognize that there’s about 15%-20% of patients who have either primary refractory disease, or progression within 24 months of initial diagnosis. Clearly, these patients have higher risk disease. We often refer to them as the POD 24, progression of disease within 24 months population. And I think that 15%-20% of patients, we’re not really sure what to do with in the second-line setting. There’s some data to suggest that, because of their disease refractoriness, they may benefit from early transplant, such as an autologous stem cell transplant, but I think the data is still not really firm. We don’t have randomized data, for example, to guide what to do with that patientpopulation, and I think it does beg the question, should we go down a more aggressive route or not? I’m still a little bit on the fence in my own clinic on what to do with that patient population.

I agree with you, and while we do know that overall the patients who experience POD 24, as a group, have inferior outcomes, I think that is partially explained by occult or undiagnosed transformation. And if you can rigorously exclude transformation from patients experiencing early relapse, it’s not as clear that their outcomes are as inferior. Those are patients that are likely to be less sensitive to chemotherapy in the second line and may benefit from either lenalidomide-based treatment, or other novel approaches, as opposed to trying another cytotoxic treatment. But I also share your uncertainty about obligatory transplant.

I agree. In my own clinic, I do just that. I make sure there isn’t an underlying transformation to explain the early progression. The data would suggest that as many as 50%-70% of patients may actually harbor a transformation. So going down a more aggressive route of alternative salvage therapy and autologous stem cell transplant would be appropriate and reasonable in that case. But if you can really exclude transformation, I do agree that pushing more chemotherapy on those patients is probably not in their best interest, but rather going to alternative targeted therapies would be more appropriate.

For me, that’s even more the case, because now we have a growing armamentarium of options for third-line patients. Knowing that you have options to turn to with a second relapse certainly takes a little bit of the pressure off, in terms of trying to be maximally aggressive in that second-line setting and putting patients at risk for complications from another transplant.

Matthew Matasar, MD and Laurie Sehn, MD, share insight on available therapies for relapsed or refractory follicular lymphoma and reflect on factors that help in treatment selection.

Laurie Sehn, MD | Authors

Articles

Follicular Lymphoma: Forecasting Bispecific Antibody Treatment Strategies

Bispecific Antibodies in Relapsed/Refractory Follicular Lymphoma: AE Management

Advent of Bispecific Antibodies for Relapsed/Refractory Follicular Lymphoma

Multiply Relapsed Follicular Lymphoma: Overview on CAR T-Cell Therapy

Novel Targeted Agents in Multiply Relapsed Follicular Lymphoma

Relapsed/Refractory Follicular Lymphoma: Second-Line Treatment Armamentarium