Consensus Recommendations Address Key Controversies in Lymphoma Management

As novel therapies are evaluated and integrated across the larger lymphoma treatment paradigm, meetings such as Bridging the Gaps in Leukemia, Lymphoma and Multiple Myeloma Consensus Conference help address key controversies and provide recommendations to supplement available guidelines in the management of malignancies such as mantle cell lymphoma (MCL), chronic lymphocytic leukemia (CLL), and diffuse large B-cell lymphoma (DLBCL), according to Alexey Danilov, MD, PhD, and Tycel Phillips, MD.

Following the inaugural meeting in 2025, Danilov, Phillips and colleagues published consensus recommendations in Cancer that emerged from expert discussions and debates.¹ Among the recommendations, experts outlined the importance of testing for TP53 mutations and other high-risk characteristics in patients with MCL; for patients with disease harboring TP53 mutations, they pointed to the phase 2 BOVEN trial (NCT03824483) regimen of zanubrutinib (Brukinsa), obinutuzumab (Gazyva), and venetoclax (Venclexta) as a potential treatment avenue.

They also recommended the use of time-limited treatment strategies for younger patients with CLL, along with an observational approach for patients with asymptomatic disease. Discussions and recommendations in DLBCL focused on sequencing considerations with emerging therapies and combinations, along with the need for additional evidence to support circulating tumor DNA (ctDNA)/minimal residual disease monitoring for disease progression.

In interviews with OncLive^®, Danilov and Phillips expanded on the key recommendations in MCL, CLL, and DLBCL published from the 2025 meeting, along with highlighting the importance of gathering different expert viewpoints to help navigate challenging areas of treatment.

Danilov is the associate director for Clinical Sciences in the Comprehensive Cancer Center, the Marianne and Gerhard Pinkus Professor in Early Clinical Therapeutics, the medical director of the Early Phase Therapeutics Program for the Systems Clinical Trials Office, the co-director of the Toni Stephenson Lymphoma Center, and a professor in the Division of Lymphoma of the Department of Hematology & Hematopoietic Cell Transplantation at City of Hope in Duarte, California.

Phillips is an associate professor in the Division of Lymphoma of the Department of Hematology & Hematopoietic Cell Transplantation at City of Hope.

OncLive: Why is conducting meetings like Bridging the Gaps to talk through some of these debated consensus points within the lymphoma space important?

Danilov: The point of this meeting is to try to address some of the gaps that exist in the management of hematologic conditions. The Bridging the Gaps meeting included experts who treat lymphoma, leukemia, and [multiple] myeloma, and while there are published guidelines that get regular updates, such as the National Comprehensive Cancer Network [NCCN] Guidelines, those [guidelines] are typically published based on hard evidence or relatively hard evidence. The reality is, in everyday practice, we encounter cases and puzzles that don't necessarily fit with the guidelines. There are substantial gaps in our understanding of how to address certain medical problems within those fields, based on, say, published NCCN Guidelines, simply due to either lack of information or controversial information that's out there based on current evidence. This is what [Bridging the Gaps] is for, where the experts [convene] and discuss these gaps. We discussed how we approach these gaps and how we manage patients where there is either controversial evidence or not enough evidence available.

Phillips: The purpose of a lot of these conferences has been to get some general consensus among investigators about the best way to manage, tackle, and treat certain hematological malignancies. For a fair number of the treatments, there are multiple options that are available within the space, and they offer a lot of variability for patients and physicians for what may be deemed the appropriate treatment. What these conferences do, as much as we can, is try to narrow down what is the appropriate options are for some of these more questionable areas, especially areas where potential treatments could negatively impact some late outcomes. We all have our own opinions, and forcing key opinion leaders or people who are considered experts in a certain area to agree on certain points is a benefit. For the field as a whole, [we want] to try to, at least, narrow down some of the options so there's just not as much controversy when it comes to making certain treatment decisions.

What were some of the key consensus viewpoints published from the 2025 Bridging the Gaps Meeting regarding MCL?

Danilov: As far as MCL is concerned, there was a very strong recommendation to [test for] certain genetic abnormalities, including TP53 mutations, complex karyotypes, and highly proliferative disease, such as a Ki-67 [level] over 50%, to identify these high-risk patients for whom a more modern regimen, such as the BOVEN regimen, would be much more appropriate. This regimen is based on a combination of BTK and BCL-2 inhibitors. There was a discussion about CAR T-cell therapy and how it is highly recommended for patients with covalent BTK inhibitor–refractory MCL. [There was also] a discussion that addressed the controversy of autologous stem cell transplant [ASCT], which at the time was quite substantial, given the [phase 3] TRIANGLE study [NCT02858258] results, which were just updated at the time that the manuscript was assembled, and there was increasing consensus among the experts at the time that the role of ASCT is rapidly diminishing. In fact, a few experts had said that ASCT has no role in the management of MCL.

Phillips: For TP53-mutated MCL, for the longest time, we've realized that there are a lot of poor outcomes with chemotherapy. There's more growing literature [indicating] that there's not a consensus about all TP53 mutations being bad. We do see some that maybe not as poorly prognostic as the majority of the TP53 mutations. All in all, we discussed the available data that we have with some of the regimens that have shown efficacy in [the TP53-mutated] space, discussing, at least at this point, some of the benefits that we see with BTK inhibitors in patients who harbor TP53 mutations, and [we are] looking forward to developing more non-chemotherapy–based regimens for patients in this space. As an aside, identifying some other high-risk patient characteristics [will be important]. We probably have not focused as much on [other high-risk characteristics] due to being laser-focused on TP53. [We want] to open it up to have further discussions about some of these other high-risk features, which probably need to be taken into account in frontline therapy.

With brexucabtagene autoleucel (Tecartus; brexu-cel) now fully approved by the FDA for the treatment of patients with relapsed/refractory MCL, what does this mean for the role of CAR T-cell therapy in MCL?² What CAR T-cell therapy recommendations were shared in the publication?

Phillips: [The approval] provides more flexibility for investigators to determine when to integrate CAR T-cell therapy. There have been quite a few discussions about using CAR T-cell therapy earlier vs just the third-line setting. I do think for most patients, the broad label [for brexu-cel] won't necessarily make a big impact. In essence, there are probably very few patients who will ever see CAR T-cell therapy before they see a [covalent] BTK inhibitor. I don't think [brexu-cel] necessarily being approved in the BTK inhibitor–naive space will necessarily make a major difference, but it offers that flexibility, at least with brexu-cel.

As we move forward, 2 things are becoming quite apparent. BTK inhibitors are being used in earlier lines of therapy, moving into the frontline space, where we will likely never really see CAR T, at least in the current format. However, in some avenues, where you may have a patient with a TP53 mutation who may, unfortunately, see chemotherapy without a BTK inhibitor or another treatment, it gives you the option of possibly bypassing the BTK inhibitor, or at least not necessarily having to [progress on] the BTK inhibitor, before going to CAR T-cell therapy. In some of these cases, we do see that exposure to chemotherapy by itself may negatively impact outcomes in patients who are subsequently treated with BTK inhibitors. Therefore, those patients may have short remissions even with the use of the BTK inhibitor. Being able to get to CAR T-cell therapy earlier would possibly allow us to save more patients, which is the ultimate goal for any of the treatments that we set out to use.

What consensus viewpoints were shared within the CLL field?

Danilov: In CLL, there was an increased interest in using a time-limited therapy approach, particularly for younger patients with favorable-risk CLL. Venetoclax plus obinutuzumab was identified as the preferred frontline regimen at the time, and acalabrutinib [Calquence] plus venetoclax was identified as an emerging option. Of course, we know the [phase 3] AMPLIFY trial [NCT03836261] regimen, acalabrutinib plus venetoclax, has now been approved [by the FDA in February 2026].³ Those consensus recommendations actually heralded this [regimen], and many experts already said at the time that they were moving on toward this [strategy].

Phillips: In the CLL space, there is a little bit different of an argument. As of right now, the biggest argument is continuous BTK inhibitors vs some of these doublet regimens. Do you think it's better to do a doublet with a BCL-2 inhibitor and BTK inhibitor? Or are you doing a doublet with venetoclax or obinutuzumab? Is it a continuous BTK inhibitor? There are a lot of different permutations you can do within the CLL space, and the good thing, at least with CLL, once you have progression on 1 line of treatment, normally, it allows you to move to a subsequent line of therapy, meaning that if you progress on a BTK inhibitor, you can then go to a BCL-2 inhibitor, or you have the option of the noncovalent BTK inhibitor, pirtobrutinib [Jaypirca]. There are BTK degraders that are being explored, CAR T-cell therapy is still there, and then there's some early data suggesting bispecific antibodies may also be effective in CLL.

What recommendations were shared in the DCBL space?

Danilov: In DLBCL there were several recommendations. The use of ctDNA was still not recommended at the time, but it was heavily discussed due to emerging data. Of course, there were quite a lot of discussion on CAR T-cell therapy for [patients with] primary refractory/early-relapsed disease, based on recent randomized trials in the second-line setting.

Phillips: For the DLBCL aspect, a lot of discussions have surrounded the evolving role of frontline therapy, [including] how to position [the phase 3] POLARIX trial [NCT03274492] regimen and what to make of some of the data we have from the POLARIX study about [treatment] preference. It appears, at least from the clinical trial, that patients with non–germinal center B-cell [GCB]–like [DLBCL] typically perform better with [polatuzumab vedotin (Polivy)] than patients who have the GCB subtype. [Regarding the positioning] of CAR T-cell therapy, we reemphasized that in the second-line space, CAR T-cell therapy should be the preferred option for patients with primary refractory [disease] and discussed how we line up treatments. For patients who unfortunately progress on CAR T-cell therapy, [we talked about] where we put these novel treatment regimens [and] the best avenue to integrate bispecific antibodies.

We also had a general discussion about what we're going to do next with all these clinical trials that will be reading out in the next couple years, as we will likely see a significant of influx of positive treatments for patients with DLBCL. That will likely be [the topic of] a future discussion. What will we do when these studies read out if they're all positive? Which [treatments] will be best for certain patients? Which are the data sets that we won't necessarily implement, whether it be due to limited benefit, cost, or increased toxicity?

With these recommendations published, how would you apply them to supplement other guidelines and data-based approaches in the lymphoma field?

Danilov: The guidelines also list the relevant evidence to help the clinician decide which approach they want to take. Even though there are certain recommendations from the consensus, there was also quite a lot of disagreement in terms of how to approach these certain problems, and that's where the body of the manuscript may be helpful, because at least some of the evidence may help convince the physician to go one route or another. It is clear that there is not always 1 correct answer to every situation, and that's where the [manuscript] may be helpful in listing several options that are available, where not a single option may be necessarily right or wrong.

References

1. Danilov AV, Coombs CC, Phillips T, et al. Clinical strategies for lymphoma management: Recommendations from the Bridging the Gaps in Leukemia, Lymphoma, and Multiple Myeloma Consensus Conference 2025. Cancer. 2026;132(8):e70389. doi:10.1002/cncr.70389
2. US FDA grants full approval of Kite’s Tecartus for adult patients with relapsed or refractory mantle cell lymphoma. News release. Gilead Sciences. April 2, 2026. Accessed May 13, 2026. https://www.gilead.com/company/company-statements/2026/us-fda-grants-full-approval-of-kite-tecartus-for-adult-patients-with-relapsed-or-refractory-mantle-cell-lymphoma