Rituximab Maintenance Therapy Post-AHCT Improves Survival for Patients with MCL

For patients with mantle cell lymphoma (MCL), while maintenance therapy with rituximab after autologous hematopoietic cell transplantation (AHCT) has been shown to extend progression-free survival (PFS), the effect of rituximab maintenance on overall survival (OS) is less clear.

To gain more clarity on the effect on OS, Soloman Graf, MD, from Fred Hutchinson Cancer Research Center in Seattle, Washington, and colleagues conducted a retrospective study of patients with MCL who underwent AHCT at three centers between November 1995 and May 2011: the University of Washington Medical Center, the Fred Hutchinson Cancer Research Center, and the Veterans Affairs Puget Sound Health Care System. They found that this therapy confers a benefit in PFS and suggest it may improve OS.

“These are the first data to show both a PFS and an OS advantage to adding maintenance rituximab after AHCT,” Ajay K. Gopal, MD, the corresponding author for the study, also from Fred Hutchinson Cancer Research Center in Seattle, Washington, told ASH Clinical News. “With a simple intervention like rituximab maintenance, we may be able to improve the natural history and survival for patients with MCL.”

A total of 157 patients were included in this retrospective study: 50 who received maintenance rituximab after AHCT and 107 who did not. The decision to administer (or not to administer) maintenance rituximab was made by the treating physician on an individual basis or as part of two separate phase II protocols.

Maintenance rituximab was given according to the following dosing schedules:

  • weekly dosing for 4 weeks every 6 months for 2-4 courses (n=15)
  • weekly dosing for a single 4-week course (n=8)
  • every 3-month dosing for 2-8 doses (n=7)

Multiple different dosing schedules were used in the remaining cases (n=20).

Patients were excluded from the study if they underwent tandem AHCT/allogeneic HCT or had inadequate data to assess receipt of maintenance rituximab.

The median patient age at the time of AHCT was 57 years (range = 35-71 years), and 85 percent of the study participants were male (n=134). Dr. Graf and colleagues indicated that there were no differences in patient baseline characteristics between those who did and did not receive maintenance rituximab.

All 50 patients who received rituximab had received it prior to undergoing AHCT, as did 13 of the 107 who did not receive maintenance rituximab following AHCT (p=0.01).

Patients received a median of eight doses of maintenance rituximab (range = 1-16 doses) at a dose of 375 mg/m2 initiated a median of 77 days following AHCT (range = 27-287 days).

Patients who received rituximab after ASCT were more likely to:

  • Have received high-dose cytarabine as a part of induction chemotherapy (p=0.02)
  • Have undergone AHCT during first remission (p<0.001)
  • Be in complete remission (p=0.002)
  • Have received conditioning without radiation (p=0.001)
  • Have undergone AHCT more recently than those who did not (p=0.009)

After a median follow-up of five years, the researchers found that maintenance rituximab was associated with both improved PFS (hazard ratio [HR] = 0.44; 95% CI 0.24-0.80; p=0.007) and improved OS (HR=0.46; 95% CI 0.23-0.93; p=0.03).

On the safety side, grade 4 neutropenia did occur at an increased rate in the maintenance rituximab group compared with those who did not receive it: 34 percent versus 18 percent, respectively (p=0.04).

“Our data encompassed a wide span of time during which additional effective therapies in MCL were introduced and may have improved OS in patients with progression of disease after AHCT,” Dr. Graf and authors noted, including proteasome inhibitors and immunomodulators, but an analysis showed no association between the time period of AHCT and the effect of maintenance rituximab on OS.

“While promising, these data must be considered in the context of a single-center, retrospective analysis,” Dr. Graf told ASH Clinical News, noting some of the current study’s limitations. “Consequently, there may exist confounding variables not entirely accounted for by the multivariate analysis and the true benefit may prove less than that described. The prospective, phase III LyMa trial is examining this strategy and maturation of its interim results are therefore awaited.”


Graf SA, Stevenson PA, Holmberg LA, et al. Maintenance rituximab after autologous stem cell transplantation in patients with mantle cell lymphoma. Ann Oncol. 2015;26:2323-2328.