Rituximab maintenance following R-CHOP tied to favourable long-term outcomes in MCL
Rituximab maintenance following first-line immunotherapy with R-CHOP* is highly effective for mantle cell lymphoma (MCL), with prolonged progression-free survival (PFS) and overall survival (OS) rates compared with interferon-alpha maintenance, according to the long-term follow-up results of the European MCL Elderly trial presented at ASH 2017.
“[C]ompeting risk analysis revealed that the efficacy of rituximab maintenance in terms of lymphoma progression prevention was substantial,” said Dr Eva Hoster from the University Hospital of the Ludwig Maximilians University of Munich, Germany.
Initiated in 2004, the European MCL Elderly trial comprised 560 patients (median age 70 years) with newly diagnosed MCL who were unfit for standard high-dose treatment (ie, cytarabine followed by autologous stem-cell transplantation). Participants were initially randomized 1:1 to receive eight cycles of R-CHOP and six cycles of R-FC** (induction phase), after which, 316 participants in the induction therapy phase entered the maintenance phase and were randomized to receive rituximab (n=155) or interferon-alpha (n=161). [N Engl J Med 2012;367:520-531]
At 5 years, 33 percent of participants were still on rituximab maintenance. In contrast, only 5 percent continued with interferon-alpha maintenance. [ASH 2017; abstract 153]
Compared with interferon-alpha maintenance, rituximab maintenance among R-CHOP recipients led to prolonged PFS (51 percent vs 22 percent; p<0.0001) and OS (79 percent vs 59 percent; p=0.0016) rates at 5 years. These findings were consistent with the initial results at 3 years (58 percent vs 29 percent for PFS and 87 percent vs 63 percent for OS).
Although rituximab maintenance following R-FC also resulted in prolonged PFS vs interferon-alpha maintenance (52 percent vs 32 percent; p=0.032), rituximab was deemed “too toxic” given the higher incidence of death, said Hoster.
The results demonstrate the advantage of R-CHOP over R-FC, noted Hoster. While there was a lower 5-year cumulative incidence of treatment failure with R-FC vs R-CHOP (51 percent vs 60 percent), the cumulative incidence of death without progression at 5 years was substantially higher with R-FC vs R-CHOP (19 percent vs 9 percent). “This discourages the use of R-FC as first-line treatment in this setting,” said Hoster.
Overall, the updated findings support the initial results showing a longer life expectancy associated with rituximab maintenance compared with those who received interferon-alpha among older patients who successfully underwent R-CHOP pretreatment. [N Engl J Med 2012;367:520-531]
“Maintenance therapy with rituximab showed not only a [PFS] benefit but also a significant survival advantage,” indicated Hoster and colleagues in the initial trial.
While the researchers suggested combining rituximab with other drugs that have shown potential in MCL treatment given its survival benefits, possible drug interactions should still be taken into consideration, they added.