Diagnosis and Frontline Management of Diffuse Large B-Cell Lymphoma

Transcript:
Matthew A. Lunning, DO, FACP: Hello, and welcome to this OncLive Peer Exchange 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.

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

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

Jason Westin, MD, MS, FACP: 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.

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

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

Matthew A. Lunning, DO, FACP: 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?

Joanna M. Rhodes, MD, MSCE: 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 MYC rearrangements, BCL2 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 TP53 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.

Matthew A. Lunning, DO, FACP: 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?

Joanna M. Rhodes, MD, MSCE: 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.

Matthew A. Lunning, DO, FACP: 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?

Ian W. Flinn, MD, PhD: 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.

Matthew A. Lunning, DO, FACP: 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?

Ian W. Flinn, MD, PhD: 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.

Matthew A. Lunning, DO, FACP: 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?

Ian W. Flinn, MD, PhD: 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.

Transcript edited for clarity.