Polatuzumab-Rituximab: RR DLBCL Ariel Perez ASH 2022 Seco...

Dr. Ariel Perez discusses Polatuzumab-Rituximab: RR DLBCL ASH 2022 Second-Line Therapy


Polatuzumab-Rituximab: RR DLBCL Ariel Perez ASH 2022 Second-Line Therapy

By Ariel Perez Perez, MD

What did the combination of Polatuzumab-Rituximab either with our without Bendamustine show in this clinical trial? So our study is a retrospective study of patients treated with Polatuzumab Vedotin which is a CD79 antibody drug conjugate in combination with Rituximab plus the addition of Bendamustine in the patient population with relapsed refractory large b-cell lymphoma (RR DLBCL).

Our aim was to analyze the institutional outcomes of patients treated with this regimen. And as well, we wanted to look at the pattern of failure to front-line therapy, meaning patients that received their initial treatment for diffuser b-cell lymphoma. The way they failed to therapy to be, for example, primary refractory disease where they never achieved a complete response or they can achieve a complete response and then relapse later on their disease (progression) course.


And we compare the objective response rate and complete response rate with this patient with primary refractory disease and those with relapses disease (progression). We studied a total of 22 patients with large b-cell lymphoma (RR DLBCL) and analyze response rate based on Lugano criteria as well as result in terms of progression-free survival and overall survival.

In terms of response, the best objective response rate was 68%, and of node 14 out of 22 patients achieved a complete response. If we look at the patterns of failure to frontline therapy, 45% of this cohort had primary refractory disease, which as we know, based on prior data analysis, it's a subgroup of patients with particular poor outcomes.


We are observed that the regiment of Polatuzumab Vedotin with Rituximab with or without the addition of Bendamustine, we saw results in objective response rate in this population. And of note, even though this regimen was initially studied in patients that were considered transplanting eligible in our dataset, we've still got patients with large b-cell lymphoma (RR DLBCL) who could be bridged to subsequent cellular therapy.


In fact, patients, 41% of patients included in our study ended up receiving either CD19 targeted CAR T-cell therapy or autologous stem cell transplantation (ASCT).


What is relapsed refractory large b-cell lymphoma?

After a period of remission, the phrase "relapsed" refers to disease that emerges or grows anew.

The term "refractory" is used to characterize lymphomas that do not react to treatment (i.e., cancer cells continue to develop) or when the response to treatment is not very long-lasting.

Patients with DLBCL whose illness is resistant to first chemotherapy or has relapsed may be treated with high-dose chemotherapy followed by stem cell transplantation. The majority of stem cell transplant patients will receive an autologous transplant (patient receives his or her own stem cells, collected prior to the procedure). Rarely, a patient undergoes an allogeneic transplant (patient receives stem cells from a donor).


What are the most common questions you are asked by your colleagues about this study?

One of the common questions in terms of this study is if there are any advantage to using Polatuzumab Vedotin based regimens earlier on, as we mentioned before, the study by our colleagues, patients, and that led to the approval. The minority of patients have at least two or more lines of therapy. In, in order, as I said, we saw that patients with large b-cell lymphoma (RR DLBCL) that received treatment in the second line setting, and as we know, we shouldn't make, this is not a comparative study, but if we look at the historical data, the response rates and the second line setting appear to be higher. And as I mentioned before, it can be an effective bridging option to therapies that have higher efficacy in the setting of relapse refractory large b-cell itself, and specifically CD19 targeted CAR T-cell therapy, which is now approved in the second line setting.


In the ZUMA-7 study, no bridging was required, but as we know, especially in community settings, these patients with progressive disease or that failed frontline therapy, it's important to count in our treatment options with something that could increase, not only provide an objective response, but also control the disease for a longer time to allow for additional therapy.


Will this data affect clinicians today?

I think the main impact of this study would be along with additional data in the second line setting, making practitioners more comfortable with prescribing Polatuzumab Vedotin based regimens earlier on the disease course. I don't think waiting until the third line or higher to try Polatuzumab Vedotin is necessarily what we need to do and if we have the option of using an earlier on as a bridge to cellular therapy, I think that's something that definitely we need to consider.


Obviously additional clinical trials are needed in this regard. But the result of this retrospective studies report that this is an effective regimen in the second line setting. And as I mentioned, one of the main things is that it could be a bridge there to additional therapy with CAR T for example.


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In fact, one of the main definitions is what therapy do you use before the patients under go therapies for CAR T? And you can call this holding therapy, for example. And in this case, I think this is one of the regimens that's most commonly used in this setting.


What is the next step for this medical research?

I think the next step for this, for our research is basically extending our cohort. So we have 22 patients treated so far and we'll continue to include patients in this cohort for analysis as we mentioned, we did look at how the pattern of failure to frontline therapy influences subsequent responses to Polatuzumab Rituximab, with or without Bendamustine.


And we also want to have additional data regarding differences and other clinical outcomes. For example, progression-free survival, and overall survival that we are presenting, but due to the limited amount of patients that I think that's one of the reasons why we don't we, even though we see differences it doesn't reach statistical significance (through statistical analysis).


And one of the other steps that we want to look at is the more patients that we have, we can look more in detail to the patterns of Bendamustine use. We know that Bendamustine can affect t-cell fitness, so in our practice for patients that have, that are undergoing or being evaluated for CD19 targeted CAR t-cell, we omit the Bendamustine for from the regimen, at least until leukapheresis is completed.


What are the key takeaways from this research and data?

I would direct, I think in terms of how to look at this data. I would reach out to community oncologists and even though in the food and drug administration (FDA) label, this is a medication that is approved after at least two prior lines of therapy. I think we should consider the use of Brolucizumab earlier on.


And there's subgroup of patients, especially those with primary refractory disease, where we know that salvage chemotherapy, even though it can lead to a total of stem cell transplantation and potentially a cure in a subset of patients with relapse refractory diffuse b-cell lymphoma. As we know, there's many patients that are not able to be salvaged.


So considering Polatuzumab Vedotin earlier on and early referral for CAR T Center evaluation for cellular therapy should be, should be considered. Target is CD79, so it also has the advantage of being a different target from CAR T cell when you are considering that as an option. And if the patient achieve a good enough response, then obviously that allows you more time in terms of additional therapy.


Final Thoughts

I think this is a therapy that it's conceived initially as a transplant ineligible population relapse refractory diffuse large b-cell lymphoma (RR DLBCL) patients, and with good outcomes in terms of results compared to chemotherapy alone with Polatuzumab and Rituximab. But in the, in the current setting, I would say we have to consider this regimen as an option earlier on in their treatment course with the goal of subsequent cellular therapy.


Ariel Perez Perez, MD - About The Author, Credentials, and Affiliations

Miami Cancer Institute hematologist and medical oncologist Ariel Perez, MD. Dr. Perez specializes in bone marrow transplant, cellular immunotherapy, and malignant hematology. He's bilingual.

Dr. Perez did a residency in bone marrow transplant and cellular immunotherapy at the H. Lee Moffitt Cancer Center & Research Institute in Tampa before joining Miami Cancer Institute. CAR T-cell treatment for relapsed refractory B-cell lymphomas was his fellowship research.

During residency and fellowship, he was chief. Dr. Perez received the Internal Medicine and Hematology-Oncology Academic Achievement Awards at Orlando Health. Medical school awards followed (Summa Cum Laude).


Dr. Perez has published in peer-reviewed journals like Transplantation and Cellular Therapy Journal, Journal of Clinical Oncology, Journal of Thoracic Oncology, and Annals of Oncology. He has presented his research at many research meetings, industrial conferences, and events.


Dr. Perez Perez prioritizes patient communication and trust while offering the best evidence-based medical care.



Lymphoma Research Foundation - Diffuse Large B-Cell Lymphoma: Relapsed/Refractory. Lymphoma Research Foundation, 2021