Analysis Identifies Predictors of Survival in Older Patients With Mantle Cell Lymphoma

Data from an analysis of approximately 1,200 patients with mantle cell lymphoma collected across 12 treatment centers presented at the 2020 ASCO Virtual Scientific Program demonstrated that maintenance Rituxan (rituximab) was associated with improved progression-free survival and overall survival, but an autologous stem cell transplant was not.

Mantle cell lymphoma (MCL), which is an aggressive B cell non-Hodgkin lymphoma, is associated with poor outcomes, especially as most patients diagnosed with the disease are older.

“Some of the unique challenges that we see with this patient population specifically is that they have comorbidities or they could be medically unfit such that intensive chemoimmunotherapy with or without an autologous stem cell transplantation, which many would argue as the standard of care for frontline treatment, is not feasible in such patients,” Dr. Reem Karmali, of Robert H. Lurie Comprehensive Cancer Center of Northwestern University, said in a recent interview with CURE®’s sister publication OncLive®. “And this, we think leads to poor outcomes in this patient group.”

Karmali discussed what the results of the analysis showed, as well as the advantages of the study.

What were the methods that were used to conduct this analysis that was presented at ASCO?

For our study, we actually looked to assess clinical outcomes and predictors of survival in patients with mantle cell lymphoma who were older, and we defined older MCL patients as 65 years of age or older. We actually collected data across 12 academic institutions, and we included over 1,100 cases of mantle cell lymphoma. Within this group, there were 465 patients over the age of 65 that were identified. And these were the patients that essentially were used for the majority of our analyses.

What did the results of the analysis show?

We followed these patients for just under … six months of completing their therapy and about a quarter of patients actually relapsed (and) about a third of these patients in the relapsed refractory setting were actually treated with a BTK inhibitor or BTK inhibitor combination therapy. And then we looked at how this translated over to progression free survival and overall survival. And the way we conducted this analysis was to look at patients based on age cohorts. We divided patients into three age cohorts. The first was age under 65. The second cohort was 65 to 69 years of age. And then the third cohort was age 70 or older. And we were able to show that two-year progression free survival and overall survival rates actually diminished with cohorts of increasing age. We then went ahead and did univariate and multivariate analyses, and on univariate analysis we saw maintenance Rituxan, the lack of use of maintenance Rituxan along with (primary refractory disease six months) and (patients who progressed within 24 months), all predicted for poor overall survival. And then when we looked at multivariate analyses, we found that maintenance Rituxan impacted overall survival significantly, as well as progression free survival. And interestingly, the use of an autologous stem cell transplantation, which was conducted in about a quarter of our patients did not seem to impact survival.

Was it surprising to find that transplant didn't impact survival?

Not so much, because I think the idea is that we probably ended up with some morbidity and mortality that kind of contributed, and sort of negated the potential positive effects of transplantation. But that is sort of a big question is whether transplantation is really needed? And that's where the cooperative group trial is, it's specifically addressing that question, although it does exclude patients over the age of 70.

Do you think that a limited number of patients who received BTK inhibitors limited the application of the analysis to the current Rituxan era?

I think that that's an important point here. It is important to note that the data predates the widespread use of BTK inhibitors and even cellular therapies such as CAR T-cell therapy, specifically. And so, it doesn't reliably reflect the potential advancements and survival that we've been able to achieve with these novel targeted therapies. But there are some elements to this study that are useful. I think that the study points out that maintenance strategies do appear to have a place. You know, this is something that we know in younger patients who have undergone stem cell transplantation followed by Rituxan maintenance, we do know that that offers a survival advantage, or we're seeing the same here in older patients and the key is going to be to optimize maintenance strategies, I think in older patients. The second thing that our study (had) an advantage of doing (was) showing us how survival is impacted in the Rituxan era. And it really serves as a historical reference for ongoing studies to which you know, we can compare impact on survival with novel therapeutic strategies.