Long-term follow-up from the Nordic phase 2 MCL2 (ISRCTN87866680) and MCL3 (NCT00514475) trials showed that frontline treatment with rituximab (Rituxan) and intensive chemotherapy could lead to a functional cure for some younger patients with mantle cell lymphoma (MCL), according to Mats Jerkeman, MD.
In a presentation at the 2025 EHA Congress, Jerkeman and colleagues presented long-term data from patients treated across the 2 studies, which demonstrated that a median follow-up of 18 years, 35% of patients (n = 319) were still in first complete remission (CR1) at last follow-up. Notably, 25% of patients were still alive and in CR1. In this overall population, which had a median age of 57 years (range, 29-67) at baseline, excess mortality was higher compared with the general Nordic population, but survival plateaued for patients under 50 years of age, suggesting no excess mortality for this group. However, Jerkeman cautioned that the population of patients under 50 years of age was a relatively small sample.
“Every physician who has a patient with MCL has this conversation: Is this a curative treatment? Is it a curable disease?” Jerkeman said. “It’s actually a difficult question to answer. However, the current answer is that yes, we think that a proportion of patients are actually cured with the current treatment. With new treatments that also include BTK inhibitors [in the] frontline, we believe that the proportion is probably higher—even if we don’t know that yet.”
In an interview with OncLive®, Jerkeman highlighted the rationale for conducting this long-term analysis and explained the potential implications of these data, and remaining treatment needs for patients with higher-risk MCL. He is head of medical oncology at Lund University and principal investigator at Lund University Cancer Centre in Sweden.
OncLive: What was the rationale for conducting this follow-up review of the Nordic MCL2 and MCL3 trials?
Jerkeman: [In] the MCL2 trial, our initial analysis [showed] a trend toward a plateau in failure-free survival. In 2008, we hoped that this was possibly a curative treatment for MCL. However, after longer follow-up, we saw that this plateau disappeared, but we always had an interest in trying to identify patients who were actually cured with this treatment.
How were the Nordic MCL2 and NORDIC MCL3 trials designed, and what patient populations were included in each study?
These were younger patients with MCL, [defined as] up to 65 years of age. They received intensive induction therapy with maxi-CHOP–based therapy in combination with high-dose cytarabine [and rituximab], followed by consolidation with autologous stem cell transplant. This [treatment approach] has since then become a standard treatment for younger patients with MCL.
What were the findings from the longer-term analysis were presented at EHA?
The median follow-up was 18 years, and we [conducted] an analysis of relative survival to see if, possibly, the survival of the study population was similar to the normal population in the countries where these trials were ongoing—the Nordic countries. When we analyzed the whole population, there was no plateau; there appears to be excess mortality, even in patients who were in CR1 after as long as 15 years. The [patients with MCL] had excess mortality compared with the matched general population.
However, when we looked at different subgroups, we found that among the younger patients—[those who] were under 50 years of age at diagnosis—there seemed to be a possible plateau. We did not observe excess mortality specifically for that small subgroup, which is interesting. We also observed that 25% of the patients were still alive and in CR1, so this is a sign of what we can call a functional cure, or clinical cure. We believe that quite a high proportion of the patients are cured with this treatment.
What unmet needs continue to persist for patients with MCL, particularly those who may not be eligible for intensive frontline therapies or who experience relapse following standard treatment approaches?
The prognosis of patients with MCL is very dependent on the biology of the tumor [and] the genetics of the tumor. Patients who have tumors that include TP53 mutations or [exhibit] blastoid histology and high proliferation have a higher risk of relapse. The current need is especially [urgent] for patients with high-risk biology [in] MCL. For that population, there is no standard treatment yet that is satisfactory. Therefore, the most important need is to define a treatment for high-risk MCL.
At the diagnostic level, what symptoms should physicians be aware of that may warrant referral for further evaluation and facilitate an earlier or more accurate diagnosis?
The typical symptoms of MCL are like [those seen] with other lymphomas. It’s [commonly characterized by] enlarged lymph nodes, but MCL can also include gastrointestinal symptoms, because MCL often involves the bowel. Patients can have diarrhea or abdominal discomfort. [MCL] can also present as lymphocytosis, which may be asymptomatic—[a presentation] very similar to chronic lymphocytic leukemia [CLL]. To differentiate [MCL] from CLL, flow cytometry of the blood is needed. Patients with enlarged lymph nodes or lymphocytosis should be referred to an expert hematologist or oncologist for further workup.
Reference
Trab T, Ekberg S, Eskelund C, et al. Can mantle cell lymphoma be cured? Insights from 25 years of follow-up in the Nordic MCL2 and MCL3 trials. Presented at; 2025 EHA Congress; June 12-15, 2025; Milan, Italy. Abstract PF880.