Addition of Polatuzumab to R-CHOP Improves Outcomes for Patients With DLBCL


In an interview with Targeted Oncology, Gustavo Fonseca, MD, FACP, discussed the positive health-related quality of life findings in patients with diffuse large B-cell lymphoma from the POLARIX study.

Gustavo Fonseca, MD, FACP

Gustavo Fonseca, MD, FACP

The phase 3 POLARIX study (NCT03274492) elicited superior progression-free survival (PFS) and a similar safety profile in patients with previously untreated diffuse large B-cell lymphoma (DLBCL) administered polatuzumab vedotin (Polivy), rituximab (Rituxan), cyclophosphamide, doxorubicin, and prednisone (Pola-R-CHP) vs rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP).

At the recent American Society of Hematology (ASH) 2022 Annual Meeting, the updated quality of life findings from the trial were presented. In the trial, a total of 879 patients with previously untreated DLBCL were randomized in a 1:1 ratio to receive either Pola-R-CHP (n = 440) or R-CHOP (n = 439).

Questionnaires were administered to patients without progression during treatment on Day 1 of Cycles 1 (baseline), 2, 3, and 5, at end of treatment (EOT), biannually for 2 years after EOT, then annually for the following 3 years.

Findings showed that in the questionnaires, response rates were high at above 80% in the study. At baseline, scores between both treatment arms were similar for lymphoma symptoms, physical functioning, and fatigue. Levels of constipation, diarrhea, nausea, and vomiting were also all similarly low.

Overall, both regimens led to rapid and sustained improvements in symptoms and improved health-related quality of life. Most patients had improvements in their lymphoma symptom scores after cycle 1. Between arms, physical functioning and fatigue scores were similar at baseline and improved during and after treatment. These data may represent a benchmark for patient-reported HRQoL in frontline DLBCL in the modern era.

In an interview with Targeted OncologyTM, Gustavo Fonseca, MD, FACP, hematologist/oncologist, medical director of the Clinical Research Program at Florida Cancer Specialists & Research Institute, discussed the positive health-related quality of life findings in patients with DLBCL from the POLARIX study.

Targeted Oncology: Can you discuss your presentation on the POLARIX study?

Fonseca: We presented in an aggressive lymphoma prospective clinical trials session, an analysis from the patient's perspective of their outcome to the treatments. This is the POLARIX study, which was Pola-R-CHP vs R-CHOP. We use what is considered validated tools to assess their response to therapy, like functional status, lymphoma associated symptoms, and quality of life. Overall, we assess these tools depending on the arm. We got almost 900 patients with this. The adherence of completing baseline after cycle, beginning of cycle 2, beginning of cycle 3, cycle 5 into therapy, bi-annually and annually, we got over almost 85% of completion rate in close to 900 patients, so it's a humongous database acquired in a prospective fashion in a modern day, so, we think this is going to be a benchmark.

The clinically important issues are that over 80% of our patients within a month showed an improvement in their lymphoma associated symptoms and we did not lose that as the therapy continued. We all, as clinicians, felt that that was the case because you are treating an aggressive lymphoma, you see the lymph nodes shrinking, but it is nice to see this prospectively acquired data, which is probably the largest in the world in this fashion. The same thing happened with improvement of the fatigue. Depending on the tool, we would see the improvement that's at the beginning of day month 1 or at the end of treatment. The good news, again, is that these gains were not lost after treatment continued. [It is] reassuring to see that there is an improvement of the quality of life, functional status, or the lymphoma associated symptoms, but also how there is no accumulated toxicity from the therapy. We're happy with that because this was from the patient's perspective, which is something that we should be more regularly involved in. Regulatory agencies can see that there is a persistence of a benefit to the patients from the patient's perspective, which is why we are so proud.

What was the basis of evaluating the patient reported outcomes associated with the POLARIX study?

The POLARIX study was published with the clinical outcomes of the comparison of the Pola-R-CHP vs R-CHOP in this past ASH. [In the session we were a part of, we discussed] the patient's reported outcomes. It is different when physicians take information and put it into the chart and then it gets extracted from our notes vs now patients are reporting it. That was 1 of the reasons why we felt so strongly about it and that's why we shout out the coordinators and patients that managed to accomplish such great adherence.

We used several tools that have been validated: the EORTC tool for quality-of-life assessment, the functional tool, and also the fatigue tool. Again, these tools have already been defined as having thresholds that are clinically significant.

What prior information is there regarding Pola-R-CHP vs R-CHOP?

Pola-R-CHP vs R-CHOP in the POLARIX study was a prospective international study which compared what has been just standard, R-CHOP, to now the selection out of the removal of vincristine because of the potential of neurotoxicity. This has now been replaced by an antibody drug conjugate, polatuzumab, where we are now targeting a different epitope on the lymphoma cells, basically, a target therapy that is expected to have a lower toxicity pattern, or at least greater effectiveness.

The disease-free survival data were reported during the last ASH. That's why this agent is being evaluated for approval by the FDA and already has been approved in the European market. The internal countries will define what setting they will utilize it in. We're very motivated by the fact that the functional improvement of the patient persisted and that there is a disease-free survival improvement with the Pola-R-CHP arm, because then, we expect that this is going to be translated and fewer patients will have to escalate therapies with other novel treatments or transplants and [chimeric antigen receptor] T cells. We think that we are in a moment of a divergence threshold fork in the road.

What are the next steps for this research?

We want to find even better options or convenient combinations with these agents. R-CHOP has been the standard for since the 70s and many studies have failed when they tried to compare novel agents or different regimens against CHOP, particularly against it since the addition of rituximab. Anything that enhances the tolerance without sacrificing the improvement of what we have accomplished with the Pola-R-CHP, would be very interesting. Targeted therapies are trying to minimize the amount of chemo, like Pola or an antibody conjugation of chemo with a monoclonal antibody and for delivery of drug in a much more pertinent or accurate way of delivery. Therefore, these functional assessments are vital, because we will see that if we don't sacrifice effectiveness, we may have an improvement of the patient's symptomatology, and that would be great.

Now we have this database and that is where we're happy with what the session reported because it's 1 of the largest, if not the largest, database acquired in modern days, with again, very high adherence of patients completing it. We can be more comfortable establishing this data to be real validity to those patients who had to go through the treatment, and then therefore, helped us to accomplish this.

What unmet needs still exist in space?

We are seeing the disappearance gradually, based on large phase 3 studies, of chemotherapy without a target. In general, we are seeing more and more that when we have targeted treatments and biological combinations, we will be leaving chemotherapy behind as a historical importance. That's what we had in the 60s and 70s and it was important compared with what we had before. Gradually as we know more and understand more about the biology, we can accomplish the same or greater improvements, outcomes in the patient's treatment, and get lower toxicity. [I am also] happy to see how this POLARIX study is not accomplished by 1 small group of individuals and [instead,] is an international effort that is patient centric. That's what we reported and therefore, something that is going to be more impactful to our patients.

Friedberg JW, Thompson CA, Trneny M, et al. Health-related quality of life (HRQoL) in patients with diffuse large b-cell lymphoma (DLBCL) treated with polatuzumab vedotin, rituximab, cyclophosphamide, doxorubicin and prednisone (Pola-R-CHP) versus rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) in the phase III POLARIX study. Blood. 2022;140 (1): 6623–6626. doi:10.1182/blood-2022-157761
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