Talal Hilal, MB, BCh
In a meta-analysis of rituximab (Rituxan) maintenance for patients with mantle cell lymphoma (MCL), investigators concluded that this approach improves progression-free (PFS) and overall survival (OS) following induction chemoimmunotherapy.
“Overall, patients who are young, fit, and eligible for transplant who start with an induction chemoimmunotherapy that includes cytarabine-based regimens and rituximab maintenance in that setting appear to have a benefit in terms of PFS and OS,” said lead study author Talal Hilal, MB, BCh.
Through PubMed, Embase, Scopus, Web of Science, and Cochrane, investigators gathered 697 records, and 28 full-text articles were used after exclusions. Overall, 1050 patients met the inclusion criteria, with 455 patients in the rituximab maintenance arm and 595 in the non-rituximab maintenance arm.
PFS (HR, 0.39; 95% CI, 0.31-0.50) and OS (HR, 0.47; 95% CI, 0.27-0.83) were improved with rituximab maintenance. Additionally, those who had undergone autologous stem cell transplant experienced a slightly better PFS (HR, 0.34; 95% CI, 0.25-0.47) and OS (HR, 0.38; 95% CI, 0.22-0.65) benefit.
In an interview with OncLive®
, Hilal, an assistant professor of Medicine at Mayo Clinic, discussed the findings of this meta-analysis, and the approach to maintenance therapy in patients with MCL.
OncLive: Can you provide an overview of this trial?
: This was a meta-analysis where we aimed to answer the question of what the benefit of maintenance rituximab is in patients who have MCL. There are not many studies, so we thought that a systematic review would be a good way to start. We found about 700 studies that were screened by about 7 meta-inclusion criteria, which were pretty broad. They did not specify whether it was a first-line treatment, relapse, or posttransplant. The main thing was that they must have had induction chemoimmunotherapy. We also included randomized trials and observational studies with comparative arms. Randomized trials were included, and 4 observational studies were included.
We found that in the overall population, there was a benefit in terms of PFS and OS. In the prospective studies only, the benefit was mainly PFS, and there was no OS benefit. There are only 3 prospective trials, and 2 of them did not use transplant. That is the main driver of the OS benefit in terms of prospective studies. Retrospective studies have their own limitations—there is a lot of heterogeneity and differences in how patients were treated. When we looked at transplant only, there were a couple that were excluded because they did not do transplants, so we were left with about 5. In those studies, there was a benefit in PFS, but not OS.
What else needs to be understood about rituximab in this setting?
There was a study presented at the 2016 ASCO Annual Meeting, which was a subgroup of the [StiL NHL7-2008] MAINTAIN trial, which looked at bendamustine/rituximab induction followed by maintenance versus observation. That is not published yet as a paper; however, in that trial, there was no benefit in PFS or OS. Those are patients who did not receive a transplant and were not fit for transplant. They received the most common induction regimen that we use, which was not reflected in this meta-analysis. A lot of clinicians don't offer maintenance rituximab in the setting of no transplant. They'll receive chemoimmunotherapy and get a response, but then it is sort of unknown.
A lot of it is unknown because this abstract did not show a benefit. That is a place that [rituximab] could be explored further. Could a more intensive chemotherapy regimen be more useful and [deliver] some sort of benefit in terms of PFS in this setting? Using cytarabine induction in patients who are younger may be a population that benefits from maintenance rituximab. It would be nice to see that paper get published, but for now, there is a consensus on offering rituximab maintenance for patients after transplant. There is a little controversy for patients without transplant.
Are there any other agents you would like to see explored?
There are data in follicular lymphoma using obinutuzumab (Gazyva) that has not been replicated in MCL. The data in follicular lymphoma are not convincing; there are limitations to using obinutuzumab, such as a high risk for infection and toxicity. Unless we can show some benefit to rituximab in OS or quality of life, it will be hard to move to a different anti-CD20.