R-CHOP Still Chosen Over Targeted Therapies in Frontline DLBCL

Jason Westin, MD, MS, FACP

Jason Westin, MD, MS, FACP

For patients with diffuse large B-cell lymphoma (DLBCL), the standard frontline treatment is rituximab (Rituxan), cyclophosphamide, doxorubicin, vincristine, prednisone (R-CHOP). Overall, the regimen has been shown to be effective among these patients, and the chemotherapy-like toxicities that develop following R-CHOP treatment are manageable. There are subgroups of patients that have suboptimal response to R-CHOP though, and these patients require more than R-CHOP alone.

At the 24th Annual International Congress on Hematologic Malignancies, Jason Westin, MD, MS, FACP, presented answers to the question, when do we need more than R-CHOP upfront in DLBCL? The main subgroup of concern are patients with high-grade B-cell lymphoma with MIK and BLC2 or BLC6 translocations. Because this subgroup of patients has a suboptimal response to R-CHOP, adjusted R-CHOP regimens, like rituximab, etoposide phosphate, prednisone, vincristine sulfate (Oncovin), cyclophosphamide, and doxorubicin hydrochloride (hydroxydaunorubicin (R-EPOCH), are used to enhance response. In patients who have other high-risk features, there are similar chemotherapy regimens to improve efficacy.

Even with the success of R-CHOP in this patient population, investigators at MD Anderson Cancer Center recognize that there are other possibilities. Currently, multiple clinical trials are underway combining 2 or more targeted agents and showing high response rates, said Westin. The data are not yet mature, but Westin stated that these studies show promise for eliminating chemotherapy in the treatment landscape of DLBCL.

The data are still immature, so we need more time to follow this up and more studies to be done, but there is potential for a chemotherapy-free future for large cell lymphoma, Westin said

In an interview withTargeted Oncology, Westin, director, Lymphoma Clinical Research, Department of Lymphoma/Myeloma, Division of Cancer Medicine, and associate professor at The University of Texas MD Anderson Cancer Center, discussed the pros and cons of administering R-CHOP in the frontline setting of DLBCL. He also discussed other options for patients who have limited responses to the standard-of-care.

TARGETED ONCOLOGY: Can you discuss the prognosis for patients with DLBCL and the role of R-CHOP in treating these patients?

Westin: The prognosis for patients with DLBCL is generally good. We are able to treat patients with a chemotherapy combination called R-CHOP. This regimen has been the standard for a long time, and we can look at several factors to decide how likely someone is to do well with this treatment. These factors are available from standard blood tests, CAT scans, and physical examinations. If these factors show that a patient is not likely to do well, sometimes we might think about doing alternate therapies.

TARGETED ONCOLOGY:What toxicities are associated with R-CHOP?

Westin: R-CHOP is a chemotherapy regimen, and it does have chemotherapy-like toxicity. These are fairly common and well-managed but include nausea, fatigue, and risk of infections like neutropenic infection with low blood counts. Most treatment centers have familiarity with managing these infections and these complications, and most patients can tolerate the full 6 cycles of the planned R-CHOP regimen.

TARGETED ONCOLOGY: What other treatment options are available in this space?

Westin: For patients with DLBCL, the other option in the frontline setting would be to modify the chemotherapy. Dose-adjusted R-EPOCH is a modified version of R-CHOP. The combination of hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (hyper-CVAD) or cyclophosphamide, vincristine, doxorubicin, high-dose methotrexate (CODOX-M) are also modified versions of R-CHOP, which are all largely based on 1970s chemotherapy.

We have tried multiple times to add targeted agents to R-CHOP, and unfortunately, this approach has failed because the chemotherapy drugs do not synergize well with new targeted agents. At MD Anderson, we're doing multiple clinical trials combining targeted agent with targeted agent for newly diagnosed large cell patients and it's showing incredible responses of above 80% without any chemotherapy, The data are still immature, so we need more time to follow this up and more studies to be done, but there is potential for a chemotherapy-free future for large cell lymphoma.

TARGETED ONCOLOGY: What are the biggest challenges with treating this patient population?

Westin: The biggest challenge in treating patient with large cell lymphoma revolve around the fact that this is very aggressive disease. Large cell lymphoma tends to be diagnosed quickly after it develops, and many patients need to receive therapy urgently.

For patients who respond to treatments, the plan is to complete 6 cycles. For patients who have a sub-optimal response, the question is what to do next. In the second-line and beyond, treatments are not as good as first-line treatments in terms of long-term responses. We need to optimize and improve the initial treatment these patients receive, and clinical trials are the best way to do that.

TARGETED ONCOLOGY: What is the key takeaway from your presentation?

Westin: The take-home message is that large cell lymphoma is the most common lymphoid cancer. Treatments are successful in the vast majority of patients. Over two-thirds of patients will be cured with an initial treatment such as R-CHOP. Lots of new medication are coming, including chimeric angitgen receptor (CAR) T cells, which may help patients who have relapsed disease or potentially influence frontline therapy in the future. The sky is the limit, and the future looks bright for patients with DLBCL.

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