Consolidative HSCT may not be necessary for some patients with mantle cell lymphoma
Click Here to Manage Email Alerts
Key takeaways:
- HSCT did not benefit patients with mantle cell lymphoma in complete remission with undetectable minimal residual disease.
- Transplantation may help those with minimal residual disease after induction.
SAN DIEGO — Autologous hematopoietic stem cell transplantation did not benefit adults with mantle cell lymphoma in first complete remission after induction, according to randomized phase 3 data presented at ASH Annual Meeting and Exposition.
Researchers stopped enrollment early, as 3-year OS rates did not differ between individuals who received auto-HSCT and those who did not.
“This data, combined with the recently published TRIANGLE trial, will allow clinicians and patients to feel comfortable omitting auto-HSCT [for] the majority of patients with mantle cell lymphoma undergoing first-line therapy,” Timothy S. Fenske, MD, MS, professor at Medical College of Wisconsin, told Healio. “This is a big step forward [because] the toxicity of auto-HSCT can be significant for these patients.”
Background and methods
Mantle cell lymphoma accounts for approximately 5% to 7% of non-Hodgkin lymphoma diagnoses, Fenske said.
Individuals with mantle cell lymphoma have long been treated with auto-HSCT during first complete remission based on findings from previous trials, according to study background.
“With older chemotherapy approaches in the 1980s and 1990s, outcomes were poor, with median survival in the 3- to 5-year range,” Fenske said.
More recently, outcomes have improved with the use of rituximab (Rituxan; Genentech, Biogen), high-dose cytarabine, auto-HSCT and maintenance rituximab.
“In some studies incorporating some or all of these advances, the average first remission is in the 8- to 10-year range,” Fenske said.
Recent research has suggested auto-HSCT may not improve survival.
“The typical patient with mantle cell lymphoma is in their mid- to late 60s, often with medical comorbidities,” Fenske said. “[For] such patients, the auto-HSCT procedure can be difficult and, in some cases, lead to life-threatening complications. Therefore, we felt it important to test whether auto-HSCT offers benefit in the current treatment landscape.
“We focused on patients who were in first complete remission and with undetectable minimal residual disease,” Fenske added. “The idea is that these patients are already in a very deep remission state and are less likely to benefit from the auto-HSCT.”
Researchers enrolled 650 adults (median age, 60 years; range, 27-71; 79% men; 92% white) with mantle cell lymphoma in first complete remission.
Researchers randomly assigned participants who had undetectable minimal residual disease (MRD) to undergo auto-HSCT plus 3 years of maintenance rituximab (n = 257; arm A) or to receive maintenance rituximab alone (n = 259, arm B).
The study’s other participants had MRD-positive complete remission (n = 49; arm C), or MRD indeterminate complete remission (n = 85; arm D). All these patients received auto-HSCT plus maintenance therapy.
OS in arms A and B served as the primary endpoint. PFS served as a secondary endpoint.
Results
At ASH, Fenske reported results of a third pre-planned interim analysis based on median follow-up of 2.7 years.
Three-year OS rates did not differ significantly between arms A and B in analyses based on all randomly assigned patients (82.1% vs. 82.7%) and all patients treated as assigned (86.2% vs. 84.8%). The HR for OS crossed the futility boundary in analyses of all randomly assigned patients (HR = 1.11; 95% CI, 0.71-1.74) and patients treated as assigned (HR = 1; 95% CI, 0.58-1.74).
Causes of death in these groups included lymphoma (4.7% for arm A vs. 3.5% for arm B), COVID-19 (5.1% vs. 6.6%) and other/unknown (5% vs. 4.6%).
PFS rates in arm A and arm B appeared comparable when analyzed by all randomly assigned patients (HR = 1.05; 95% CI, 0.71-1.56; 3-year PFS, 76.6% vs. 77.4%) and patients treated as assigned (HR = 0.95; 95% CI, 0.59-1.54; 3-year PFS, 81.5% vs. 80.4%).
“I was not entirely surprised by the results since the value of auto-HSCT in mantle cell lymphoma has been questioned in recent years,” Fenske said. “I did expect that it might take another 1 to 3 years for the results to mature. However, the data safety monitoring committee and our statistician carefully analyzed the data before determining that the data should be released and the study closed due to lack of difference in survival in the two randomized arms.
“We need to follow the study for several more years to ensure that the results remain the same with long-term follow-up,” Fenske added.
In Arm C, results showed 3-year OS of 81.9% (95% CI, 69.6-96.4) and 3-year PFS of 76.9% (95% CI, 64.4-91.7).
In Arm D, results showed 3-year OS of 85.1% (95% CI, 76-95.4) and 3-year PFS of (62.7-85.9).
An exploratory analysis of MRD-positive patients showed all 17 who converted to undetectable MRD after auto-HCT remained alive and progression free at 3 years. Among the 13 patients who remained MRD positive after auto-HCT, 63.6% remained alive at 3 years and 48.8% remained progression free.
“Those who achieved undetectable MRD post-transplant had significantly improved outcomes — survival and progression-free survival — [compared with] those whose MRD remained detectable,” Fenske said. “This suggests that perhaps auto-HSCT may still be beneficial [for] patients with detectable MRD following induction. Further study would be needed to prove this.”
Future role of MRD
MRD has not been part of standard approaches to evaluate which patients should undergo transplant, but these data may “allow practitioners to do that,” Fenske said.
“It could be practice changing,” he added.
The role of MRD in lymphoma and lymphoid malignancies is evolving, according to Laurie H. Sehn, MD, MPH, clinical professor at BC Cancer Centre for Lymphoid Cancer and University of British Columbia.
“We have a lot of accumulating data showing that MRD can be prognostic and differentiate patients who will have good outcomes vs. those who have less favorable outcomes, but there has been a paucity of trials in the randomized setting that actually used that information to allocate different treatments,” Sehn, who was not involved with the abstract Fenske presented, said during an ASH press briefing. “This study ... is really where many areas of the field should be going. It is really a proof of concept that MRD can be a very valuable tool to allow us to direct tailored approaches to patients and allow us to spare toxicity [associated] with some of our approaches.”
For more information:
Timothy S. Fenske, MD, MS, can be reached at tfenske@mcw.edu.
Perspective
Back to Top
This is good news. For patients with mantle cell lymphoma, for front-line therapy, there will be ways to avoid getting a transplant — either for patients on certain combinations of drugs or certain patients who have achieved minimal residual disease negativity. Is it surprising? The TRIANGLE study already has suggested that there is a route to avoid transplant. They did it by adding a Bruton tyrosine kinase (BTK) inhibitor, and they’re basically proposing that as standard of care. There are now multiple BTK inhibitors. We have ibrutinib (Imbruvica; Janssen, Pharmacyclics), acalabrutinib (Calquence, AstraZeneca), zanubrutinib (Brukinsa, BeiGene) and covalent inhibitors. We have pirtobrutinib (Jaypirca, Eli Lilly & Co.), a noncovalent inhibitor. And now we have BTK degraders. That’s part of the future. Which of these BTK inhibitors are going to work best? For what patients? And what’s the basis for resistance? Those are the questions that must be answered.
Collapse
Fenske TS, et al. Abstract LBA-6. Presented at: ASH Annual Meeting and Exposition; Dec. 7-10, 2024; San Diego.
Click Here to Manage Email Alerts