Is There a Role for AHCT Consolidation in MCL in the Rituximab Era?

The availability of rituximab-containing induction regimens for patients with mantle cell lymphoma (MCL) has improved outcomes, but younger, transplant-eligible patients may benefit from consolidative autologous hematopoietic cell transplantation (AHCT), according to results from a retrospective analysis published in the Journal of Clinical Oncology. Investigators reported that consolidative AHCT was associated with longer progression-free survival (PFS) compared with no AHCT, while only a select group of patients had improved overall survival (OS) with AHCT consolidation.

“In most academic centers in the U.S., the de facto standard of care for young patients with newly diagnosed MCL has been to treat with aggressive induction therapy followed by consolidation with AHCT,” corresponding author Stefan K. Barta, MD, from the University of Pennsylvania, told ASH Clinical News. However, he noted, “this approach is based on an earlier randomized study that was conducted before the rituximab era, which showed an improvement in PFS in patients consolidated with AHCT after induction.”

With the present study, Dr. Barta and colleagues retrospectively reviewed outcomes for 1,029 younger patients (≤65 years) who were transplant-eligible at the time of MCL diagnosis to assess the impact of consolidative AHCT on survival. All participants underwent and responded to induction therapy between the years 2000 and 2015.

Patients’ median age was 57 years (range = 22-65 years), and the authors noted that both the group that underwent AHCT consolidation and group that did not were balanced regarding prognostic features, tumor characteristics, and treatment modalities. The most common induction regimens were intensive (e.g., hyperCVAD, maxi-CHOP, DHAP; 44%) and CHOP-like (43%), followed by bendamustine-based regimens (11%). Nearly all patients (973; 95%) received an anti-CD20 monoclonal antibody with induction, and 306 (30%) received maintenance rituximab.

A total of 657 patients (64%) underwent AHCT consolidation within six months of induction. Of the 372 patients who did not undergo AHCT, reasons included physician choice (67%), patient preference (18%), and “other” (e.g., mobilization failure; 3%).

After a median follow-up of 6.3 years (range = 1-205 months), the median PFS and OS for the entire cohort were 62 months (range = 1 month to 17.1 years) and 138 months (range = 1 month to 17.1 years), respectively.

“[Our study] calls into question whether all young and fit patients with newly diagnosed MCL need to receive an AHCT post-induction.”

—Stefan K. Barta, MD

Median PFS was 75 months among AHCT recipients, compared with 44 months among nonrecipients (hazard ratio [HR] = 0.64; 95% CI 0.54-0.78; p<0.01). In multivariate regression analysis, AHCT was associated with improved PFS (the study’s primary endpoint; HR=0.54; 95% CI 0.44-0.66; p<0.01), but the authors observed only a statistical trend toward improvement in OS (HR=0.77; 95% CI 0.98-1.01; p=0.06).

This relationship also was noted across subgroups: Consolidative AHCT improved PFS for all groups, but improved OS only in patients with higher-risk disease, in those who received CHOP-like induction, who had blastoid or pleomorphic morphology, or who had not received cytarabine with induction (TABLE).

Table 2: Factors Associated With Improved Overall Survival in AHCT Recipients

The researchers also conducted a propensity-score weighted (PSW) analysis to reduce inherent biases of retrospective analyses and control for disease severity. Of the 1,003 patients included in the PSW analysis, consolidative AHCT again prolonged PFS (78 months vs. 48.5 months; HR=0.70; 95% CI 0.59-0.84; p<0.05), but there was no statistically significant improvement in OS (147 months with AHCT vs. 138 months without; HR=0.87; 95% CI 0.69-1.10; p=0.24).

“Our study showed a PFS benefit but did not find an OS benefit,” Dr. Barta reported. “This calls into question whether all young and fit patients with newly diagnosed MCL need to receive an AHCT post-induction.” While certain patients with high-risk factors may benefit from an aggressive initial therapy, he added, an aggressive approach may not be necessary for all patients with MCL.

In the entire cohort, 21 patients (2%) developed acute myeloid leukemia or secondary myelodysplastic syndromes; the incidence of these secondary malignancies did not differ according to AHCT status (2.5% with AHCT vs. 1.3% without; p=0.36), although the study may not have been powered to show such a difference. The mortality rate within 100 days of consolidative AHCT was 1.2%.

“Toxicities, both short- and long-term, may be avoided [by foregoing AHCT], especially as many patients can potentially be salvaged with modern biologic and more targeted therapies,” Dr. Barta noted. “Our data may inform the individualized discussions that oncologists have with their transplant-eligible patients about [their treatment options].”

As the authors noted, the retrospective nature of the analysis limited the study’s findings. A lack of data regarding reasons patients did not undergo AHCT and the lack of standardized response assessment to induction represent other limitations of the study.

“The next important step will be to identify which patients do not benefit from AHCT,” Dr. Barta concluded. “Genetic studies and measurement of minimal residual disease after induction may provide important prognostic information to direct and inform therapy.” Prospective, randomized clinical trials comparing consolidation with or without AHCT are currently enrolling patients and should provide answers to these questions, he added.

The authors report no relevant conflicts of interest.

References

Gerson JN, Handorf E, Villa D, et al. Survival outcomes of younger patients with mantle cell lymphoma treated in the rituximab era. J Clin Oncol. 2019;37:471-80.

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