Standard of Care for Relapsed/Refractory DLBCL

John M. Burke, MD: Welcome to this OncLive® News Network® presentation broadcasting from across the country. Today’s discussion will be focused on systemic therapy for relapsed and refractory diffuse large B-cell lymphoma.

I am Dr John Burke from Rocky Mountain Cancer Centers in Aurora, Colorado. Joining me today in this discussion are my colleagues Dr Julio Chavez from Moffitt Cancer Center in Tampa, Florida; Dr Nathan Fowler from The University of Texas MD Anderson Cancer Center in Houston, Texas; and Dr Greg Nowakowski from the Mayo Clinic in Rochester, Minnesota.

During the next 45 minutes, we are going to discuss emerging treatment options for diffuse large B-cell lymphoma after disease progression and the questions surrounding how to use these novel approaches in clinical practice. Without further ado, we’ll go ahead and get started.

Dr Nowakowski, I’m going to have you get us started. Tell us about the prognosis of patients with relapsed large cell lymphoma. What factors do you look at? How do you counsel your patients? How do you, in your institution, approach chemotherapy choices for patients with relapsed disease who are both transplant eligible and transplant ineligible?

Grzegorz S. Nowakowski, MD: Thanks, John. With frontline therapy with R-CHOP [rituximab, cyclophosphamide, hydroxydaunorubicin hydrochloride, vincristine, prednisone], we cure about 60% of patients. Unfortunately, about 40% of the patients would relapse, and typically they relapse within the first year or 2, so that’s relatively quickly. We know the outcomes of those patients unfortunately remain very poor. The analysis from SCHOLAR-1 study showed that the median survival was approximately 7 months for patients with refractory disease, and only about a quarter of the patients were alive about 2 years postrelapse. This is also true if you look at a lot of other databases and retrospective analyses in this patient population, so we clearly need better therapies for those patients.

In general, the approach of those patients followed the pattern of being eligible for high-dose intensive chemotherapy. If the patients are eligible for intensive salvage chemotherapy, followed by high-dose chemotherapy in transplant, that’s still standard of care in this setting.

There are other factors that play a role in patients eligible for this therapy. This is primarily age, comorbidities, organ function, and performance status. There could be some other factors, including patient preference, in terms of the selection for the transplant.

In the long term, the outcome of those patients is still not as good as we hope for. Only about 50% to 60% of the patients will have good enough response to intensive salvage chemotherapy, to later proceed to transplant, and still even after transplant, approximately 40% will relapse. At the end, relatively few people will benefit from this approach, but we have now a lot of historical data. That is basically the curative approach in this setting and still remains the standard of care. This standard-of-care approach has recently been challenged by CAR [chimeric antigen receptor] T cells and some novel approaches that we will discuss later. However, that’s still standard of care for patients who are transplant candidates.

If you look at the patients who are not transplant candidates, those patients are typically candidates for palliative chemotherapy or targeted therapies. With new approvals in this space, we consider those therapies to be largely still not curative. The goals of those therapies are mainly palliative.

The CAR T cells are being more recognized as a potential new modality in this patient group as well. This is moving forward because we have better ways of dealing with CAR T-cell toxicity. Perhaps over time we’ll see that more of those patients might be candidates for CAR T-cell approaches.

However, there is a still a very large group of patients who would be eligible for CAR T cells, not eligible for transplant, and the options here are quite limited. It’s clearly an unmet need in diffuse large B-cell lymphoma at this point. Fortunately, and we’ll discuss it later as well, another new therapy is coming in this space.

You also asked about biological factors that predict outcomes of patients in relapsed/refractory diffuse large B-cell lymphoma. This is actually interesting because in the frontline setting, cell of origin, the ABC vs GCB subtype, double-hit status—so presence of MYK and BCL2 or BCL6 translocation or even triple hit—they are prognostic. Those patients don’t do as well with R-CHOP [rituximab, cyclophosphamide, hydroxydaunorubicin hydrochloride, vincristine, prednisone] chemotherapy, and they have a higher relapse rate.

However, the relapse itself is a bad event that seems to be almost an equalizer for biological prognostic factors. If you look at cell of origin or some other predictors, they don’t necessarily predict poor prognosis in those patients because unfortunately the majority of the patients who have relapsed and refractory diffuse large B-cell lymphoma will not do well.

John M. Burke, MD: Dr Chavez, at your institution, what is your approach to transplant-eligible patients? Do you have a standard chemotherapy salvage regimen that you use there?

Julio Chavez, MD: We have a few regimens out there that are being used for salvage chemotherapy, like ICE [ifosfamide, carboplatin, etoposide] or rituximab, ESHAP [etoposide, methylprednisolone, cytarabine, cisplatin] or DHAP [dexamethasone, cytarabine, cisplatin]. We use GDP with consistent gemcitabine, cisplatin, and dexamethasone in combination with rituximab. I found this a little more tolerable. There is actually a trial showing that the quality of life and the recovery time for patients is better, and the efficacy is not less than the standard like ICE [ifosfamide, carboplatin, etoposide] or ESHAP [etoposide, methylprednisolone, cytarabine, cisplatin]. It’s easy to give to because day 1, day 8, the patient doesn’t have to be admitted. They don’t have to come every day to do chemotherapy. There are some considerations to keep in mind, like we see more hematology toxicity, especially thrombocytopenia, as well as electrolyte abnormalities like hypomagnesaemia and hypokalemia with cisplatin. I would caution for older patients, especially over age 70, because they may have more renal toxicity. Very rarely you see ototoxicity now in head and neck cancers, but this is something to consider too.

John M. Burke, MD: Dr Fowler, anything to add?

Nathan H. Fowler, MD: When thinking about what to use as salvage for these patients, I look at 3 main things. One is, as Julio mentioned, is the performance status of the patients to see if they’re eligible. The other things would be looking at what their first-line regimen was and how long that first-line regimen lasted.

I generally think of patients that are primary refractory to induction therapy as unfortunately having a pretty low likelihood of responding to salvage chemotherapy. I still use R-ICE [rituximab, ifosfamide, carboplatin, etoposide] or R-DHAP [rituximab, dexamethasone, cytarabine, cisplatin] in those patients. Very quickly, in fact even as I’m screening them, giving them ICE [ifosfamide, carboplatin, etoposide] or DHAP [dexamethasone, cytarabine, cisplatin], I’m thinking about CAR T-cell therapy. This is because those are the patients who unfortunately usually don’t do that well, even with salvage standard chemotherapy.

Transcript Edited for Clarity