DLBCL: Circumstances for Deviating Away From R-CHOP

Ian W. Flinn, MD, PhD: Hello, and welcome to this OncLive® Peer Exchange®, “The Evolving Treatment Landscape in Relapsed and Refractory Diffuse Large B-Cell Lymphoma.”

I’m Dr Ian Flinn, from the Sarah Cannon Research Institute in Nashville, Tennessee. Joining me today in this discussion are my colleagues: Dr John Burke, from the Rocky Mountain Cancer Centers in Aurora, Colorado; Dr Kami Maddocks, from The Ohio State University Wexner Medical Center in Columbus, Ohio; Dr Amitkumar Mehta, from the University of Alabama Birmingham Comprehensive Cancer Center [O’Neal Comprehensive Cancer Center at UAB]; and Dr Loretta Nastoupil, from The University of Texas MD Anderson Cancer Center in Houston, Texas.

Today we are going to discuss a number of topics pertaining to the use of novel agents in relapsed/refractory diffuse large B-cell lymphoma. We’ll discuss newly available agents, the latest research in the field, including from the ASH [American Society of Hematology] 2020 virtual meeting, and the impact of recent clinical trials on making decisions around treatment selection.

Let’s get started on our first topic. John, perhaps we’ll start with you. R-CHOP [rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisone] is really the mainstay of our therapy for most patients, or for many patients with diffuse large B-cell lymphoma in the frontline setting. But under what circumstances would you use a different regimen, and why would that be?

John M. Burke, MD: I would say, Ian, there are probably a few circumstances I can think of when I might use regimens different from conventional R-CHOP [rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone]. Examples would include to treat the so-called double-hit or triple-hit lymphomas. For those patients, my practice has generally been to use dose-adjusted EPOCH [etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin] with rituximab. Certainly, other regimens are reasonable as well in that high-risk subgroup. We know that those patients fare poorly with R-CHOP [rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone]. We do not have randomized trials demonstrating improvement in outcome with any other regimens. We have a number of retrospective studies that suggest that some of the more aggressive regimens may lead to better outcomes in those patients who don’t do well with R-CHOP [rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone]. One of those is the dose-adjusted EPOCH [etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin] regimen. Another is rituximab plus hyper-CVAD [cyclophosphamide, vincristine, doxorubicin, dexamethasone]. The third is rituximab plus CODOX-M/ IVAC [cyclophosphamide, vincristine, doxorubicin, methotrexate/ifosfamide, etoposide, cytarabine.

I find that subgroup to be challenging to really know what to do with. In many areas in our field, we don’t accept results of retrospective analyses as being the gold standard. I don’t think there really is a gold standard. Simply because of relatively unfavorable outcomes with R-CHOP [rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone] and the fact that the best we have are these retrospective data, I think one of the more aggressive regimens is reasonable to use. I tend to use dose-adjusted EPOCH-R [etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, rituximab] in my practice, which is a community practice. I can administer that treatment as an outpatient procedure without having to hospitalize patients. That’s a scenario for which I’ll use something different from R-CHOP [rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone].

Another is in primary mediastinal large B-cell lymphoma. Most studies have suggested that while R-CHOP [rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone] is acceptable, the risk of local recurrence may be higher without radiation. Patients with primary mediastinal large B-cell lymphoma are frequently younger women. Radiation may result in some long-term toxicities, including coronary disease and higher risk of breast cancer. The dose-adjusted EPOCH-R [etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, rituximab] regimen has been shown to be a highly effective regimen without the use of radiation therapy. And again, in the nonrandomized trial very good results have been seen with that regimen. So I’ll choose the dose-adjusted EPOCH-R [etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, rituximab] regimen in that group.

HIV-associated lymphoma might be another scenario for which one may consider using dose-adjusted EPOCH-R [etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, rituximab], although R-CHOP [rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone] is still acceptable. I don’t treat a lot of HIV-associated large B-cell lymphoma—I just don’t see a lot of it—but I have used dose-adjusted EPOCH-R [etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, rituximab] in that group.

Ian W. Flinn, MD, PhD: John, let me break in here and get a few other people on board here.

Amit, he mentioned several different groups. There are the double-hits, the primary mediastinals, HIV. What about other groups for you? Do you use any of the prognostic factors? We talked a little about FISH [fluorescence in situ hybridization] testing, looking at the double-hit cases, but are there other groups for which you might use something different?

Amitkumar Mehta, MD: All of the regimens use anthracycline, one of the important chemotherapies. There are 2 groups I can think of: One group is those patients who have a heart-related issue. For instance, if they have CHF [congestive heart failure]. In those patients, we cannot use anthracycline no matter what the risk factors are. In that case, we have to supplement anthracycline, classically we use doxorubicin, with something else.

There are many regimens that have been discussed. One of them is EPOCH [etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin] with a low dose of anthracycline we could use, or supplement gemcitabine in place of anthracycline. The other group that is an area of unmet need, so to speak, in my opinion, is the elderly population. These are patients who cannot handle full-dose CHOP [cyclophosphamide, doxorubicin, vincristine, prednisone] or EPOCH [etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin]. Consistently, if you look at the frontline study when they compared head-to-head R-CHOP [rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone] with rituximab dose-adjusted EPOCH [etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin], the outcomes were similar, but the toxicity was higher in the EPOCH [etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin] group. So if you have an elderly patient who cannot handle full-dose CHOP [cyclophosphamide, doxorubicin, vincristine, prednisone] or dose-adjusted EPOCH [etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin], using mini-CHOP [cyclophosphamide, doxorubicin, vincristine, prednisone] or a reduced-dose of CHOP [cyclophosphamide, doxorubicin, vincristine, prednisone] has been my practice.

Transcript Edited for Clarity