MCL Treatment: Differences Exist Between Trial-Based Recommendations and Real-World Care

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Research found discrepancies between treatment recommended by clinical trial results and treatment that is typically given to patients with mantle cell lymphoma.

There are discrepancies between real-world care that patients typically receive and recommendations based on clinical trials when it comes to the treatment of patients with mantle cell lymphoma (MCL), according to Dr. Peter Martin.

Results from a study presented during the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting, showed that such discrepancies were notable in patients aged 65 years and younger, in that only 30.5% were treated with a cytarabine-containing chemotherapy regimen, and 23.3% underwent stem cell transplant. Additionally, among patients who were aged 65 years or older, approximately 65% received treatment with Bendeka (bendamustine) and Rituxan (rituximab) or R-CHOP.

Moreover, the real-world average time to next treatment for patients younger than 65 years was 28 months and 22.3 months in patients older than 65 years, which appeared worse than what has been reported with standard therapies in this population. These results suggest a need to focus on developing treatments that can be delivered effectively in the real-world setting, according to Martin.

“MCL is clearly a complicated (disease), and many different presentations and patient factors are worth consideration,” Martin said. “Community physicians have their work cut out for them when they are dealing with someone who has MCL. Fortunately, there are many who are willing to help, and more educational programs than ever before. Many of us who work in community or academic practices are easy to get ahold of and happy to see someone, talk to them, and give them (our opinions).”

In an interview with OncLive®, a sister publication of CURE®, Martin, chief of the Lymphoma Program at the Meyer Cancer Center and an associate professor of medicine at Weill Cornell Medicine, discussed discrepancies in real-world patterns of care for patients with MCL and what can be done to overcome them.

OncLive®: Why was it important to examine real-world treatment patterns and outcomes of previously untreated patients with MCL in US routine clinical practice?

Martin: Over the past decade, we have seen some significant improvements in the outcomes of patients with MCL who are treated in the context of clinical trials. This, of course, (includes) generally younger patients treated with more intensive induction, consolidation, and maintenance strategies, (as well as) older patients treated with bendamustine and rituximab-based strategies. (However,) we know very little about how patients in the real world are managed in the United States, particularly those who are (receiving care) outside of major academic centers. We performed this study to evaluate patterns of care.

Additionally, we were interested in the treatment outcomes of patients treated with standard-of-care regimens outside of academic centers. Separately, we were interested in (knowing more about) the role that stem cell transplantation plays in younger patients.

What were the methods utilized for this study?

This was a retrospective, observational study that used the Flatiron data set. The Flatiron group extracts medical records, in this case, for (patients with) MCL; this roughly (included) about 4000 patients treated from January 2011 to January 2021. Eighty percent of these patients were treated in community practice settings, and those data were then (plugged) into computer software, which helped us perform statistical analysis.

What were some of the key takeaways from this research?

There were really three highlights. (First), we found that the practice patterns that you might expect based on clinical trials were not necessarily met (in clinical practice). For example, among older patients, we found that (approximately) 40% were treated with bendamustine/rituximab-based therapy. Of the younger patients, only one-quarter were treated with high-dose cytarabine, and there might be different reasons for that. One reason might be that we have not done the best job of communicating with general practitioners about what kinds of therapies they should be using; that is one possible scenario. Another scenario is that many of the patients we are seeing in community practices are not the types of patients who were typically enrolling on clinical trials held at academic centers. Both of those, may play some role (in this discrepancy), and both have significant implications with respect to how we approach future research studies and educational programs.

Second, potentially related to that, we found that outcomes in patients in the Flatiron dataset were not consistent with the outcomes that we have found in clinical trials. They are, unfortunately, not as good. That (finding) suggests that we need to (consider) how we can develop treatment regimens that are likely to be administered more broadly and have the potential to be more effective.

Lastly, we defined a patient population who were stem cell transplant eligible; these were patients who were younger than 65 years of age and who had not received other lines of therapy within six months of treatment initiation. These were, theoretically, patients who responded to their induction treatment, and who could have gone on to receive a stem cell transplant. Interestingly, when we looked at those patients, no difference in outcomes associated with receipt of stem cell transplantation (was observed).

What are the clinical implications of these findings?

The most relevant finding is directed toward those who are designing clinical trials. When we design clinical trials, it is important for us to understand that these trials are being developed to treat patients who (will) be treated in the community. If we design regimens that cannot be delivered there, either because the patients (are) not being eligible for them, or we design something that is too complicated, then we have not done anyone any real favors. We need to think about that.

Are any next steps planned, or other efforts underway to examine real-world outcomes in this patient population?

Another related question that we asked from the same data set was the role of rituximab maintenance therapy (on outcomes), particularly after bendamustine-based induction therapy. We know that rituximab maintenance after R-CHOP–based therapy in older patients has been associated with an improvement in overall survival (OS; patient survival, regardless of disease progression). Similarly, rituximab maintenance after autologous stem cell transplant has been associated with an improvement in OS. There has only been one randomized trial after bendamustine induction therapy, and this was a very small trial with (approximately) 50 patients in each arm; it did not show a benefit in terms of either progression-free survival (PFS; length of survival without disease getting worse) or OS. That is, frankly, a little bit unexpected based on the other data that exist.

Since then, several groups around the world have attempted to look at observational, retrospective datasets, and that is exactly what we did here. Those data were presented at the 2021 (European Hematology Association) Virtual Congress and they do, in fact, suggest that there may be a benefit to rituximab maintenance therapy after bendamustine/rituximab induction.

That is also consistent with the data that we saw from the phase 2 E1411 trial, which (examined) bendamustine/rituximab-based induction followed by rituximab-based maintenance (and showed that) the median PFS was approximately five years; that is a little bit better than what we would expect (to see) from bendamustine/rituximab, (which) would typically be more like three years. We may not have randomized trials, but from my perspective, if we do not have a reason to not treat someone with rituximab, then we probably should.

This article was originally published on OncLive as, “Discrepancies Between Real-World Patterns of Care and Recommendations Based on Clinical Trials Exist in MCL.”

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