Relapsed/Refractory DLBCL Treatment Landscape

Brian Hill, MD, PhD: For patients who have relapsed or refractory diffuse large B-cell lymphoma [DLBCL], the standard of care remains second line, sometimes called salvage chemotherapy, usually with a platinum-based regimen such as R-ICE [rituximab, ifosfamide, carboplatin, etoposide] or R-DHAP [rituximab, dexamethasone, cytarabine, cisplatin].

About half of patients who have relapsed or refractory DLBCL, who receive salvage or second-line platinum-based chemotherapy, will achieve a remission. Those patients are most appropriate to be referred on to consolidation, high-dose chemotherapy with autologous stem-cell transplant.

Of the patients who then go on to transplant, probably about 40% or in some series about half, will have a durable remission. But remember, only about half of the relapsed patients make it to transplant. So we’re talking about less than 1 of 4 patients with relapsed disease actually being cured with a standard salvage approach.

Second, for patients who receive second-line chemotherapy and fail to have an adequate response to let’s say a platinum-based regimen—such as R-ICE [rituximab, ifosfamide, carboplatin, etoposide], R-DHAP [rituximab, dexamethasone, cytarabine, cisplatin], or maybe rituximab with gemcitabine and oxaliplatin—it’s another regimen.

For those patients, the outcome has historically been extremely poor with very short overall survival measured in months. Over the past couple of years, since 2018, we’ve had FDA approval of anti-CD19 CAR [chimeric antigen receptor] T-cell therapy, which is the most appropriate treatment for patients who do not respond to second-line chemotherapy.

Andre Goy, MD: Yes. Polatuzumab vedotin is an antibody-drug conjugate, humanized anti-CD79B monoclonal antibody, conjugated into MMAE(?). CD79B is a B-cell specific marker expressed on the surface of a number of lymphomas but particularly diffuse large cell lymphoma. As I mentioned, this was a treatment that was done in patients with relapsed/refractory, not candidates for transplant. In 40 patients per arm, the CR [complete response] rate was 40% versus 50%. It was a clear advantage in the duration of response, PFS [progression-free survival], and overall survival. This was relatively easy to tolerate. This is a population that is sometimes difficult because they have received several lines of therapy. But there is an ongoing phase 3 POLARIX trial that is trying to integrate this in a complex frontline setting to compare with R-CHOP [rituximab, cyclophosphamide, hydroxydaunorubicin hydrochloride, vincristine, prednisone]. This is really going to be an important aspect, particularly because these patients might not be candidates for doxorubicin. Who knows, in the future that might be an option for these patients.

Julio Chavez, MD, MS: As we mentioned before, there will be a significant percentage of patients who will not respond to standard chemotherapy such as R-CHOP [rituximab, cyclophosphamide, hydroxydaunorubicin hydrochloride, vincristine, prednisone], and the standard of care for those patients is to receive chemotherapy followed by autologous transplant. However, this standard of care may not be applicable for all patients for many reasons, such as comorbidities, old age, access, or patients cannot get into a transplant center, for instance. The same applies for other regimens that are currently approved, like the CAR T-cell therapy, in which again the logistics, the cost, and the access will be a challenge for them.

In that regard, treatment options for ineligible patients for CAR T-cell therapy or transplant are needed. One of the agents that are approved, polatuzumab in combination with bendamustine and rituximab, is an interesting option for patients because it can be done in the community. Community doctors are familiar with the administration of BR [bendamustine, rituximab], and polatuzumab is a monoclonal antibody that has been approved for over 6 months already, and oncologists are familiar. It’s a time-limited therapy option, so patients don’t have to be on indefinite therapy, which is a convenience. But it’s not a curative option. That should be considered.

Other agents that are in the pipeline, like tafasitamab, is also an outpatient option. One of the disadvantages is that while it has good overall response rates, patients have to remain on treatment. So in theory, we cannot talk about cures with this regimen. Finally, selinexor, which is a recently approved regimen, is oral. The advantage is it’s not an IV [intravenous], you don’t need a line; however, some of the toxicity profile remains challenging because it’s a new agent and the doctor has to be familiarized with the agent. Also, its efficacy—in my opinion, it’s a modest efficacy, about 31% response rate, a little over 10% to 15% CR rates. That is the information that physicians need to know, that they can transmit to their patients in order to make a decision.

Transcript Edited for Clarity