 Dr Wang, in your practice, are patients with diffuse large B-cell lymphoma [DLBCL] either primary refractory to their frontline therapy or relapsing quickly thereafter?

 We typically say we cure about two-thirds of patients with standard immunochemotherapy. It used to be R-CHOP [cyclophosphamide, doxorubicin, prednisone, rituximab, and vincristine], and now we just heard it would probably be pola-R-CHP [polatuzumab , cyclophosphamide, doxorubicin, prednisone, and rituximab], and that left us about one-third of the patients who will have refractory disease or will have relapsed after the initial response. The primary refractory disease has different definitions across different literature, but basically they’re either not responding enough to the frontline therapy, or they’ve relapsed early. You can argue about what’s early, but that’s about probably 10% of patients. Then you have probably another 20% or 30% of patients who relapsed within the first 2 years, but [are] not in a primary refractory bucket. Then at the 2-year mark, we usually say, we’ve probably cured most of the patients, but then if you start the clock again at that point, there is still about 9% to 10% risk of relapse in the next 5 years, counting from the 2-year mark. So, adding that together is probably again one-third of patients who will have refractory or relapsed disease.

 Could you rank [the] risk factors [you assess] when you see a new patient to say, this person is at a high risk of having primary refractory or early relapsed large-cell lymphoma?

 There are high-risk features that predict less chemotherapy-responsive disease but may not necessarily differentiate when they will relapse or become refractory to the disease. Certainly, the high-risk features, the traditional clinical risks like high IPIs [International Prognostic Index scores], disease bulk, and then, from the molecular standpoint as we just mentioned, the MYC and BCL2 expression or the 

 rearrangement, some of the high-grade B-cell lymphomas, those are the ones. With more sequencing, we’ll probably know [of more] high-risk mutations like 

. Then as you go to frontline therapy, in the first couple of cycles, probably the kinetics 2 response in the interim, may have some implication, [to] identify those who may relapse later as well.

 Dr Saeed, we just heard about the up-front treatment, [that the] paradigm may be changing. There’s been an absolute explosion of treatments for relapse/refractory DLBCL. How has all that energy, all that therapeutic energy that’s been put into the relapse refractory large-cell space, changed your practice over the last several years?

 It changed the way I look at patients right after treatment with the frontline therapy. At this point it’s important to recognize those patients who have refractory disease, who have positive imaging findings that might need follow-up right after finishing chemotherapy. It changed how I follow up on them right after treatment for the first year or two. It’s important to recognize those patients who relapse early. Unfortunately, I still feel that we don’t have good guidance on how we check and find those patients. I think we still, in clinical practice, must wait for them to have symptoms that would indicate disease relapse. I look forward to hearing more and more about the use of genetic markers in the blood, such as minimal residual disease or cell-free DNA, because I think those will help down the road to recognize those patients earlier so that we can find the best treatment for them earlier. As Dr Wang mentioned, we cure around two-thirds of those patients, but for the last one-third, we must do a better job in recognizing and finding them early because we will open many more doors for them rather than waiting for them to present with significant disease burden before we can intervene and treat them.

Videos

Key opinion leaders share a broad perspective on relapsed/refractory diffuse large B-cell lymphoma and the current treatment landscape.

Overview of Relapsed/Refractory DLBCL and Management Strategies 

 titled, “Translating Recent Evidence to the Real-World Management of Relapsed/Refractory Diffuse Large B-Cell Lymphoma.” I’m Matthew Lunning, associate professor, Division of Oncology and Hematology, and assistant vice chancellor for clinical research. I’m joined today by a panel of experts in diffuse large B-cell lymphoma. I would like to welcome my esteemed fellow panelists to introduce themselves.

 I’m Dr Joanna Rhodes, and I’m at the Rutgers Cancer Institute of New Jersey.

 My name is Yucai Wang, I’m a lymphoma doctor in Rochester, Minnesota, working for the Mayo Clinic.

 Hi, I’m Dr Jason Westin from MD Anderson Cancer Center in Houston, Texas. I’m the director of lymphoma clinical research and section chief for aggressive lymphomas.

 I am Ian Flinn, director of the Lymphoma Research Program at the Sarah Cannon Research Institute in Nashville, Tennessee.

 And I’m Hayder Saeed. I’m a lymphoma doctor at Moffitt Cancer Center in Tampa, Florida.

 Welcome, everyone, and thank you for joining me. Today we’re going to discuss several recent updates in the treatment of diffuse large B-cell lymphoma. We will discuss the data in the context of the treatment landscape and its impact on clinical practice. Let’s get started on the first topic. Dr Rhodes, I’d like you to walk us through your thoughts on when you see a pathology report or the clinical history that gets sent to you by a new patient coordinator about a [patient with] large-cell lymphoma. What are the characteristics that you’re looking for in the disease as well as in the patient?

 Outstanding question. I think any of us at this table would say that no two diffuse large B-cell patients are alike. Whether or not it’s from the clinical perspective or even from the pathologic perspective, when I’m looking through everything, I’m looking for things that give me pause about perhaps having high-risk features or concern for relapse after frontline therapy; genomic markers like 

 rearrangements. I know we don’t call it double-hit lymphoma anymore, but the new classification system is a little bit more challenging. If you get NGS [next-generation sequencing] panels, things like 

 mutations, and then clinically bulk of disease, whether or not there’s extranodal disease, and also just the rapidity with which someone comes in and the sort of cadence of their lymphoma progression.

 Are you now calculating an IPI [International Prognostic Index] score for everybody, or is that still something that you’re doing just to help your fellows out in retrospective reviews?

 I calculate the IPI. I don’t know if it’s always something that I necessarily take into consideration when I’m choosing [a regimen] again. Most of the time we are still going with an R-CHOP [cyclophosphamide, doxorubicin, prednisone, rituximab, and vincristine] backbone, but it is something that I think about when I am counseling my fellows. I don’t really talk about IPI scores with my patients. I think it gives them too much anxiety.

 Dr Flinn, when you get a diagnosis of diffuse large B-cell lymphoma in your clinic, what are the diagnostic strategies that you’re looking for? Are you always going for an excisional biopsy or an incisional biopsy, or can you get away with a core [biopsy] nowadays?

 An incisional or excisional biopsy is the preferred approach, but on a practical basis, that’s often not possible. Generally, when patients come to me, a lot of times they’ve had core biopsies, so [it is about] making sure that the pathologist has enough material to do all the appropriate studies. In this case, to me, in the most appropriate studies, you want to rule out a double-hit type of lymphoma, making sure they have enough material for FISH [fluorescence in situ hybridization], enough material for flow cytometry, and so forth. If that’s true, then I can often get by with a core biopsy.

 Does that change if a patient is a concern for relapse or refractory disease? Do you do less? Could you go with an IR [interventional radiology]-guided biopsy or are you still considering going with an excisional biopsy for the same purpose?

 If you already have a well-documented large-cell lymphoma, from the initial diagnosis, then you can often get by with less material. The question is, [what if] someone has a transformed follicular lymphoma, follicular 3A, follicular 3B? Sometimes it’s important to get more tissue at that time.

 Very good. We’ve talked a little bit about IPI score and getting at double-hit versus non–double-hit diffuse large B-cell lymphoma. Dr Westin, we know that a monumental shift or paradigm shift in frontline large-cell lymphoma treatment has possibly occurred. Could you walk us through your thoughts on the recent POLARIX [trial] data [NCT03274492] and how it’s impacted your practice?

 The longstanding frontline therapy of R-CHOP, which is CHOP, was developed in the 1970s, and rituximab was added about 20 years ago. It looks like it might be shifting to the polatuzumab-R-CHP [polatuzumab, cyclophosphamide, doxorubicin, prednisone, and rituximab] regimen based upon the POLARIX data set. In [patients with ] IPI [scores of] 2 to 5 there was a small but statistically significant improvement in progression-free survival without a significant increase in toxicity. That’s basically a trade-off of getting a little bit more activity, but not losing anything in terms of toxicity. So I think the effect size was smaller than most of us would have liked; 6.5% percent at 2 years translates to maybe 1 out of 15 patients having a different outcome [when treated] with R-CHOP versus polatuzumab-R-CHP, but at the end of the day, that is a statistically significant improvement, and I think that will be used in a frontline setting in IPI [scores of] 2 to 5.

Expert panelists open their discussion on diffuse large B-cell lymphoma by reflecting on diagnostic strategies and the frontline treatment armamentarium.

Diagnosis and Frontline Management of Diffuse Large B-Cell Lymphoma

Joanna M. Rhodes, MD, director, the Chronic Lymphocytic Leukemia (CLL) Research and Treatment Center, Northwell Health Cancer Institute, discusses evaluating the unmet needs of elderly patients inCLL.

Despite advancements with targeted therapy, the adverse event (AE) profiles of such agents are still not widely understood, Rhodes says. Moreover, elderly patients and those with comorbidities are more likely to discontinue treatments with targeted agents due to these AEs, Rhodes explains.

Although dose reductions or adjustments can help manage AEs, there is a lack of prospective data on the impact of these strategies on patient outcomes, Rhodes continues. Additionally, ibrutinib (Imbruvica) and venetoclax (Venclexta) discontinuation data were gathered from patient cohorts, Rhodes notes. However, these data were not an accurate representative of the elderly patient population and may not lead to an accurate prediction of outcomes, Rhodes concludes. 

Joanna M. Rhodes, MD, discusses evaluating the unmet needs of elderly patients in CLL. 
 

Joanna M. Rhodes, MD, MSCE

Articles

Overview of Relapsed/Refractory DLBCL and Management Strategies

Diagnosis and Frontline Management of Diffuse Large B-Cell Lymphoma

Dr. Rhodes on Evaluating the Unmet Needs of Elderly Patients in CLL