In an interview with Targeted Oncology, Peter Martin, MD, discussed the real-world findings and how future agents should be developed to ensure optimal benefit for all patients with mantle cell lymphoma.
The outcomes of patients with mantle cell lymphoma (MCL) treated with bendamustine and rituximab (Rituxan) or who underwent stem cell transplant (SCT) treated in real-world settings, primarily at community-based practices, were found to be inconsistent with outcomes observed in clinical trials.
Findings of a retrospective real-world analysis of 3455 adult patients treated between January 2011 and November 2020 show that patients in the real world fare worse than those treated in prospective clinical trials. These results underscore the need to develop novel therapies that can be delivered effectively in the community setting, according to Peter Martin, MD, who presented the data during the European Hematology Association (EHA) Congress 2021.
The patient population retrospectively evaluated included 1,036 patients under the age of 65 and 1,910 who were 65 years of age or older. In the younger group, 243 had undergone SCT. In the older group, only 75 had undergone SCT. Of the patients who received at least 1 line of treatment, chemoimmunotherapy was the most common. Aside from bendamustine/rituximab, 17.4% received rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP), and 14.1% received a cytarabine-containing regimen. There were also 667 patients who were administered rituximab maintenance.
Outcomes showed that median time to the next treatment was significantly higher for patients who had SCT. Specifically, in younger patients, the 36-month time to next treatment was 40% (95% CI, 36%-44%) in the no SCT group versus 63% (95% CI, 57%-71%) among those who underwent SCT. In older patients with MCL, those who had no SCT had a 36-mont time to next treatment in 37% (95% CI, 35%-40%) compared with 63% (95% CI, 51%-77%) among those who underwent a transplant.
Further, the data showed that overall survival was improved in the transplanted population when compared with those who did not undergo SCT. In younger patients with MCL, the 36-month OS was 75% (95% CI, 72%-79%) in the no SCT population versus 86% (95% CI, 81%-91%) in the SCT group. Older patients had a 36-month OS of 61% (95% CI, 58%-63%) in the no SCT group compared with 82% (95% CI, 72%-92%) in the group that underwent SCT.
In an interview with Targeted OncologyTM, Martin, associate professor of Medicine and chief of the Lymphoma Program at Weill Cornell Medicine, discussed the real-world findings and how future agents should be developed to ensure optimal benefit for all patients with MCL.
TARGETED ONCOLOGY: What patient outcomes are you seeing with the FDA-approved therapies available for MCL?
Martin: MCL is a fairly heterogeneous type of lymphoma, where some people present with a lymphoma that can be observed for several years. Other people's form of MCL is considerably more aggressive, and they can progress very quickly.
In clinical trials that maybe tend to enroll a slightly more homogeneous population, we see outcomes that have consistently improved over the years, so that in younger patients treated with intensive induction consolidation maintenance regimens, we have remission durations that will often last 7 to 9 years.
Data recently presented by Mitchell R. Smith, MD, PhD from the phase 2 ECOG-ACRIN E1411 trial (NCT01415752) demonstrated that in primarily older patients treated with abendamustine/rituximab backbone, followed by rituximab-based maintenance with a median progression-free survival about 5 years, those are probably the most standard approaches currently used today for MCL.
Can you provide background on the real-world analysis you presented on during the EHA Congress?
We reported on data from the Flatiron dataset. Eighty percent of patients came from community-based practices, which was a total of about 4,000 patients. We looked at the data with 3 goals in mind. One was to evaluate patterns of care to know what treatments are actually being applied. We also wanted to look at patient outcomes to see how well the patients fare when treated in general practice mostly outside of clinical trials. Third, we were curious about the role of autologous stem cell transplantation in younger patients. Separately, we also looked at rituximab maintenance.
What were the findings of this analysis?
What we found was expected to some degree. We found that practice patterns did not entirely parallel what you might expect from clinical trials. So, we discussed what we would expect from clinical trials and what we found was that of older patients, probably only about 40%, are currently treated with bendamustine/rituximab. In younger patients, it was only about a quarter of all patients who are treated with cytarabine-based induction, but those numbers are a little bit lower than what you might expect based on guidelines and clinical trials.
Similarly, we found that the outcomes of patients were also not consistent with what you would expect from clinical trials. An average time to next treatment in a 2-year timeframe in both older and younger patients was a little bit longer in younger patients and a little bit less than older patients. It was nowhere near the 5- to 7-year remission durations that we have come to expect from clinical trials.
Lastly, we also found that the role of stem cell transplantation is quite reasonably being questioned in clinical trials. So, if we looked specifically at the population of patients that were called stem cell transplant-eligible, these were younger patients who did not initiate a second therapy within the first 6 months. We asked the question, if they got stem cell transplant, or they did not, how well do they do? Similarly, regardless of whether they got the stem cell transplant, it doesn't tell us that 1 treatment approach is better than another. The study is not designed to do that. But it does support the ongoing phase 3 trials that are asking the question of whether stem cell transplantation is necessary. That provides more rationale to support enrollment in those clinical trials, and it does support the development of clinical trials that don't necessarily include intensive therapy in younger patients.
Based on this research, how would you advise community oncologists on how to shift practice so that it aligns with what has been observed in clinical trials?
It's an important question of whether we can use this data to tell people what to do, and I we can. What it does is it begs the question of why we're seeing these differences? I have friends that practice in the community and they’re referring patients that are often extremely complicated. So, I think it's likely that there are some patients who are more complicated than we might see typically in an academic practice, and more complicated than would be typically enrolled in a clinical trial. We have to understand that just like lymphoma is heterogeneous, the patient population is at least as equally heterogeneous. We need to think about how to best develop treatment regimens that serve those patients. I think it's also possible that we need to be doing a better job of developing strategies to help educate patients, or community physicians on what are the appropriate treatment options for MCL. Clearly, we can always do better with that. Working through large organizations like ASH and ASCO is probably also helpful.
What is your key takeaway from your research?
The key takeaway from my research is that as researchers, we need to be thinking about designing treatment regimens that can be practically given and that will be given to the broader patient population, both in academic and community practices. By doing this, everybody can benefit from the development of new and exciting treatments.
Martin P, Wang M, Kumar A, et al. Real-world treatment patterns and outcomes of 3455 previously untreated mantle cell lymphoma patients in us routine clinical practice. Presented at: 2021 European Hematology Association Annual Meeting; June 9-17, 2021; Virtual. Abstract EP798