A Focus on Frontline Treatment in Patients With DLBCL

Grzegorz S. Nowakowski, MD: Hello, and welcome to this OncLive Peer Exchange®titled “Applying New Data to Treatment Selection in Patients With Relapsed/Refractory Diffuse Large B-Cell Lymphoma.” I’m Grzegorz Nowakowski, a lymphoma physician and a professor of medicine at Mayo Clinic in Rochester, Minnesota. I’m joined by a panel of my colleagues who treat patients with DLBCL [diffuse large B-cell lymphoma].

Frederick Locke, MD: Hi, my name is Fred Locke. I’m coming to you from Tampa, Florida, where I’m the vice chair of the department of blood and marrow transplant and cellular immunotherapy at Moffitt Cancer Center.

Grzegorz S. Nowakowski, MD: Dr Jacobson?

Caron Jacobson, MD: I’m Caron Jacobson from the Dana-Farber Cancer Institute in Boston, Massachusetts. I’m a lymphoma physician and the medical director of our cell therapy program.

Grzegorz S. Nowakowski, MD: Dr Lunning?

Matthew Lunning, DO, FACP: I’m Matt Lunning from the University of Nebraska. I’m a lymphoma physician and the medical director of our cellular therapy program.

Grzegorz S. Nowakowski, MD: And Dr Gordon?

Leo Gordon, MD: I’m Leo Gordon from Northwestern University at the Robert H. Lurie Comprehensive Cancer Center in Chicago, Illinois. I’m a professor of medicine and the director of our stem cell laboratory.

Grzegorz S. Nowakowski, MD: Let’s start with the frontline therapy of diffuse large B-cell lymphoma. We know that DLBCL is extremely heterogeneous in clinical presentation and molecular characteristics, which results in heterogeneous outcomes. How do you use this classification and risk stratification in everyday care of patients with DLBCL? I’ll start with Dr Gordon.

Leo Gordon, MD: Thanks, Greg. This has been somewhat of an evolution. In the early days, we evolved to treatment with CHOP [cyclophosphamide, doxorubicin, vincristine, prednisone], initially based on factors that were identified by Margaret Shipp, MD, in about 1993 or 1994 with the International Prognostic Index [IPI]. Those were the clinical features that we had. We had done a study comparing CHOP with m-BACOD [methotrexate, bleomycin, doxorubicin, cyclophosphamide, vincristine, dexamethasone] a couple of years before then and identified LDH [lactate dehydrogenase] as a major prognostic factor.

We had the International Prognostic Index. We had clinical factors like that and LDH. We also had limited treatment options; so over the years, we have evolved. Obviously, we have more understanding of the molecular biology of the disease and the microenvironment to where we now have cell-of-origin analysis and molecular analyses. All of that was identified about 20 years ago. We’re still, in a way, stuck with CHOP or R-CHOP [rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone]. At the moment, we’re still using fairly simple classification schemes. Things are evolving, mostly for clinical trials. I don’t think that practice has changed yet based on cell of origin, but what we have is fodder for new clinical trials for some of the new understanding that we’re getting.

Grzegorz S. Nowakowski, MD: Thank you. Matt, you mentioned that R-CHOP has been there for a long time. Is there any other clinical situation where you’d use R-CHOP for treatment of your patients with newly diagnosed diffuse large B-cell lymphoma?

Matthew Lunning, DO, FACP: It’s important to realize that once that diagnosis is rendered, there’s a second step: taking the tissue and analyzing for what we call double-hit or triple-hit biology in the new WHO classification. That’s high-grade B-cell lymphoma with MYC rearrangements in either BCL2 or BCL6. It’s important to note that it’s got to be MYC first and then BCL2 and BCL6 in order to fall into that category. In those situations, I’d still use dose-adjusted EPOCH-R [etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, rituximab]. It’s an infusional regimen. It’s a little more resource intensive, but despite some of the dose-adjusted EPOCH-R versus R-CHOP, the CALGB [Cancer and Leukemia Group B] study, I still favor that regimen in that population.

What’s a little tougher is when you have MYC rearrangement but you don’t have that partner. Where is that and what you do? That’s still a territory that makes me uncomfortable, but sometimes I’ll err on the side of giving dose-adjusted EPOCH-R. Sometimes I’ll give R-CHOP, but I use the IPI score to help guide me in that situation. The other learning point is that “dose adjusted” is in EPOCH [etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin] for a reason. That’s the recipe. I’m not sure you’re getting the same results if you don’t have the intent to dose-adjust up, and you could be more toxic to the regimen if you aren’t checking CBCs [complete blood counts] twice weekly and not dose-adjusting down to that regimen.

Grzegorz S. Nowakowski, MD: Double-hit lymphoma and triple-hit lymphoma is definitely associated with worse outcome when treated with R-CHOP. At our institution, we tend to use Burkitt-like chemotherapies for patients younger than 60. Have any of you been using the same practice?

Leo Gordon, MD: We haven’t. We have probably used dose-adjusted EPOCH, but a lot of this is based on retrospective data. Adam Petrich, [MD,] did a paper in 2014, and the best regimen—all retrospective—was hyper-CVAD [cyclophosphamide, vincristine, doxorubicin, dexamethasone]. It wasn’t actually dose-adjusted EPOCH. It’s a good question. We haven’t done that. Like Matt, we have also used dose-adjusted EPOCH. But the caveat is there haven’t been—and I’m not sure there will be—any prospective studies comparing the regimen. These are all retrospective. In fact, there have been some retrospective studies comparing CHOP with dose-adjusted EPOCH without much difference. That brings about a question. There are some data—I think from the Lunenburg Lymphoma Biomarker Consortium—suggesting that if the MYC partner isn’t an immunoglobulin partner, the outcome is maybe not as dire. Do any of you use that to help make decisions?

Matthew Lunning, DO, FACP: I’ve tried to talk to my pathologist about looking to see if the partners, the kappa or lambda light chain—there’s literature on that as being the mysterious partner in those—but I too remember seeing those data that said that if the partner isn’t there, then you can give R-CHOP–based therapy.

Leo Gordon, MD: Sometimes in people whom I’m surprised to find are double-hit—for example, somebody who’s 78 years old with stage I DLBCL and underlying comorbidities—I’m looking for that information to give myself a reason to perhaps not use dose-adjusted EPOCH. That’s the way I’m doing it at the bedside. I first make the decision and then I support it by the data, if you will.

Grzegorz S. Nowakowski, MD: Dr Jacobson, do you use IPI? The FLYER Study showed that younger patients with low-risk factors can be treated with abbreviated chemotherapy. Do you use it in your practice?

Caron Jacobson, MD: I do, but I find that there are still a lot of exceptions in the patient population that was put on the FLYER Study. I feel like all the patients who come in with a low IPI have an unusual extranodal site that I feel less comfortable giving abbreviated chemotherapy for. I definitely would do it for the right person, but there are some exceptions to it that I’m not sure the study was robust enough to evaluate.

Transcript edited for clarity.