Chicago, IL—Maintenance therapy can improve overall survival (OS) in older and younger patients with mantle-cell lymphoma (MCL), based on current experience with rituximab (Rituxan) therapy, but the optimal dose and dosing schedule remain under investigation.
Novel maintenance treatment strategies in MCL under investigation also show promise as new approaches to maintenance therapy; these include ibrutinib (Imbruvica) as a single agent or in combination with autologous stem-cell transplant (ASCT), as well as lenalidomide (Revlimid) as a single agent, said Brad S. Kahl, MD, Professor of Medicine, Washington University School of Medicine, St. Louis, MO, at the 2017 ASCO annual meeting.
Explaining the need for maintenance treatment in MCL, he said, “We don’t have induction therapies that are good enough yet in MCL, because the remissions aren’t as durable as we’d like them to be. In that, MCL is kind of an ideal lymphoma to test maintenance, because it is a disease that is relatively easy to get into but harder to keep there.”
Ibrutinib has impressive single-agent activity in MCL, Dr Kahl said. In older patients with MCL, ibrutinib is being studied in the SHINE trial, which has enrolled 520 patients. After induction therapy with bendamustine (Treanda) plus rituximab (BR) or BR and ibrutinib, patients are receiving maintenance therapy with rituximab alone for 2 years or with rituximab for 2 years plus ibrutinib administered indefinitely. The results are expected in 2018 or 2019.
Ibrutinib is also being investigated in combination with intensive strategies as part of the TRIANGLE study, a 3-arm study that will compare ASCT alone, ibrutinib maintenance therapy alone, and ASCT plus ibrutinib maintenance treatment.
Lenalidomide has also demonstrated single-agent activity in MCL in clinical trials and has been combined with rituximab in induction and maintenance strategies; it has shown to be a promising noncytotoxic approach, Dr Kahl said. The US Intergroup trial E1411 is investigating the use of 2 years with single-agent rituximab versus 2 years of rituximab plus lenalidomide in older patients with MCL. The primary end point is progression-free survival (PFS), with results expected in 2019.
Rituximab Maintenance Therapy
With follow-up of approximately 8 years, 50% of the 30 patients receiving induction chemotherapy with vincristine followed by maintenance therapy with rituximab as part of the Wisconsin Oncology Network study are alive without disease progression, and have not had a relapse beyond 5 years.
More recently, maintenance treatment with rituximab performed as well as ASCT as a postremission therapy strategy, with a 5-year PFS of 56% and a 5-year OS of 80%, although patients who were assigned to rituximab maintenance therapy were older and had higher scores on the Mantle-Cell Lymphoma International Prognostic Index than those who had ASCT.
“These uncontrolled trials show that maintenance is potentially very powerful in MCL; it could improve your PFS just as much as a stem-cell transplant could,” said Dr Kahl.
Maintenance treatment with rituximab in MCL began to gain widespread acceptance after the findings from the European MCL Consortium, which included patients aged ≥60 years. In this study, maintenance treatment with rituximab significantly improved the duration of remission versus interferon-alpha in patients who responded to the R-CHOP (rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine, and prednisone) regimen as induction therapy.
The benefit of rituximab maintenance therapy after the BR regimen in older patients with MCL, however, is uncertain. Among patients with MCL enrolled in the NHL7-2008 study, rituximab extended median PFS after BR treatment versus observation (72.3 vs 54.7 months, respectively), but the difference was not significant, and only 122 patients were randomized to the maintenance portion of the trial.
“I do worry that this trial is not definitive, because it is subject to quirks of small numbers when you have such a small sample size; but it is fair to say at this time, there are no data supporting maintenance rituximab after a BR induction,” he said.
In younger patients <65 years, the LyMa trial demonstrated that maintenance rituximab after induction therapy with R-DHAP (rituximab, dexamethasone, high-dose cytarabine, and cisplatin) followed by ASCT significantly prolonged event-free survival compared with observation at 4 years (78.9% vs 61.4%, respectively; hazard ratio [HR], 0.46; P = .0016) and OS (88.7% vs 81.4%; HR, 0.5; P = .045).
“At our institution, we have adopted this practice based upon this data set,” Dr Kahl said.