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SAN DIEGO — Patients with mantle cell lymphoma (MCL) and undetectable minimal residual disease (uMRD) after induction therapy did not live longer if they underwent hematopoietic cell transplantation (HCT), a randomized trial showed.

After a median follow-up of 2.7 years, patients treated with rituximab (Rituxan) and transplantation had a 3-year overall survival (OS) of 82.1% versus 82.7% among patients who received only rituximab. Progression-free survival (PFS) at 3 years also did not differ significantly between the two groups. Separate analyses of all patients and only those treated according to protocol yielded similar results.

A separate analysis of patients with detectable MRD status after induction suggested that those who converted to uMRD after transplantation did live longer, reported Timothy Fenske, MD, of the Medical College of Wisconsin in Milwaukee, at the American Society of Hematology (ASH) annual meeting.

“In the era of highly effective induction and maintenance regimens for mantle cell lymphoma, patients with undetectable MRD … did not benefit from consolidation autologous transplantation,” Fenske said during a press briefing. “The patients who remain MRD positive after induction may benefit from [autologous] transplant. In particular, the patients who converted to undetectable MRD post-transplant appear to have improved survival and progression-free survival. I would emphasize that longer follow-up will be important to confirm that these findings hold up.”

Following the presentation, Fenske said no consensus existed about the value of stem cell transplant in the setting of uMRD when the trial started. However, younger, fit patients with MCL would often undergo stem cell transplant. Use of MRD to inform treatment decisions also was not standard practice.

“I think [the study] could be practice changing, because if there is a small subset that may still benefit from transplant that we can identify with MRD testing, I think it may be important to identify those patients,” he said. “At the same time, we can spare the majority, because among the patients we tested for MRD, over 70% were MRD negative. If we can safely spare those patients from the potential toxicities of transplant, I think that’s a big step forward.”

“Historically, I think it’s somewhere in the range of 1-2% of patients who die from complications of transplant, and other patients will experience toxicities and effects on their quality of life. For some of our patients going through that, I think that alone will be a big step forward.”

Press briefing moderator Mikkael Sekeres, MD, of the Sylvester Comprehensive Cancer Center and University of Miami in Florida, asked Fenske whether MRD testing should be standard of care for determining transplant eligibility.

“Second, if [patients are] MRD negative in your practice, will you now eliminate the transplant decision as an option?” asked Sekeres.

Said Fenske, “Based on our data and also based on the recently published TRIANGLE study in Europe, we have two studies that suggest that we can safely omit the stem cell transplant in the majority of patients. I do think that identifying the MRD-positive patients is important, since it does appear that those patients may still benefit from transplant. In my practice, I would do this testing so that we can differentiate these two populations.”

Patients with MCL in first remission often undergo transplantation, a strategy based on nonrandomized phase II studies and one randomized trial. The issue has become controversial with the emergence of more effective therapies for MCL, said Fenske. Two years ago at ASH, a report from the TRIANGLE study group showed that HCT for MCL in first remission led to inferior failure-free survival as compared with single-agent ibrutinib (Imbruvica) or the Bruton’s tyrosine kinase inhibitor plus HCT.

Fenske reported primary findings from the EA4151 trial, designed to determine whether HCT benefits patients with MCL in deep first remission. Investigators in the multicenter North American trial determined patients’ MRD status by means of an immunoglobulin high throughput assay with sensitivity of 1 x 10^-6.

All patients began treatment with rituximab-containing induction therapy. Those who achieved uMRD status were randomized to autologous HCT plus rituximab for 3 years or to rituximab alone. Patients with detectable or indeterminate MRD status underwent HCT and received 3 years of rituximab.

Data analysis included 650 patients: 516 with uMRD, 49 with MRD-positive status, and 85 with indeterminate MRD status. The futility boundary was an OS hazard ratio of 0.984 for the comparison of HCT plus rituximab versus rituximab alone.

An OS analysis that included all randomized patients yielded a hazard ratio of 1.11. An analysis limited to the 375 patients who actually received assigned treatment produced a hazard ratio of 1.00. The 3-year OS values for the per-protocol analysis were 86.2% with HCT and 84.8% with rituximab alone.

The hazard ratios for 3-year PFS were 1.05 for all patients and 0.95 for the per-protocol analysis. Absolute values were 76.6% with HCT and 77.4% without and 81.5% versus 80.4%.

An exploratory analysis of OS in the MRD-positive patients showed a 3-year OS of 100% with HCT and rituximab in 17 patients who converted to uMRD after transplantation. That contrasted with 63.6% for patients who remained MRD positive. The 17 patients also had a 3-year PFS of 100% versus 48.8% for the patients who remained MRD positive.