Analysis Shows AHCT Leads to Improvements in PFS in Younger Patients With MCL

James N. Gerson, MD

Autologous hematopoietic cell transplantation (AHCT) consolidation after induction therapy may improve progression-free survival (PFS) in younger, fit patients with mantle cell lymphoma (MCL), according to the results of a retrospective analysis recently published in theJournal of Clinical Oncology.

No statistically significant improvement in overall survival (OS) could be observed, however, after propensity score—weighted analysis.

“…in this cohort of > 1,000 young, transplantation-eligible patients treated in the rituximab era, the use of consolidative autologous hematopoietic cell transplantation after induction was associated with improved progression-free survival even after controlling for disease severity using propensity score—weighted analysis,” the study authors, led by James N. Gerson, MD, of Fox Chase Cancer Center, wrote. “Although no improvement in overall survival was observed for the entire cohort after propensity score–weighted analysis, certain high-risk patients and those who did not receive intensive induction or cytarabine with induction seemed to benefit.”

The researchers sought to discover the true benefit of AHCT consolidation on survival outcomes in younger patients with MCL who were treated in the so-called rituximab (Rituxan) era.

They reviewed the data of over 1000 patients from 25 academic medical centers to find those that fit their inclusion criteria. Eligible patients were those who were no more than 65-years-old, newly diagnosed with MCL, considered transplant eligible at diagnosis, received induction therapy between 2000 and 2015, and had achieved a partial response (PR) or complete response (CR) to induction therapy. A total of 1029 patients were included, and 64% (n = 657) of these patients went on to receive AHCT consolidation after their induction therapy.

The median age at diagnosis was 57 years (range, 22-65) and 77% of patients were male. A majority of the patients had low-risk MCL International Prognostic Index (MIPI) scores, but MIPI scores were missing for 21%. Bone marrow involvement was seen in 79%, 89% were positive for cyclin D1, and 13% had a blastoid or pleomorphic morphology. Sixty-five percent had normal cytogenetics, but cytogenetic information was missing in 24%.

Induction regimens included a CHOP-like regimen in 43% of patients; intensive chemotherapy in 44% consisting of hyperCVAD, maxi-CHOP, or DHAP; and a bendamustine-based regimen in 11%. Ninety-five percent received an anti-CD20 monoclonal antibody with their induction regimen, which the authors noted confirmed that this population was treated with modern therapy. In addition, 46% received cytarabine with their induction therapy and 3% received a novel agent. Maintenance rituximab was given to 30% of patients.

Seventy-six percent achieved a CR from induction therapy and the rest had a PR.

The 2 groups of patients, those who underwent AHCT and those who did not, were mostly balanced with regard to prognostic characteristics.

Unadjusted analysis showed statistically significant PFS and OS improvements with AHCT after induction therapy. The median PFS was 75 months in patients who underwent AHCT compared with 44 months in those who did not (hazard ratio [HR], 0.64; 95% CI, 0.54-0.78;P<.01). The median OS was 147 months with AHCT consolidation and 115 months without AHCT (HR, 0.79; 95% CI, 0.63-0.99;P<.05).

Multivariable regression analysis showed improved PFS with AHCT and a trend toward improved OS. The HR for PFS was 0.53 (95% CI, 0.43-0.66;P<.01) and the HR for OS was 0.77 (95% CI, 0.98-1.01;P= .06).

On subgroup analysis, all subgroups demonstrated an improved PFS with AHCT consolidation. An association with improved OS was seen in the subgroups with high-risk MIPI scores, patients who received CHOP-like induction, those with blastoid or pleomorphic morphology, and patients who did not receive cytarabine.

&ldquo;This suggests that patients who do not receive cytarabine with induction, receive CHOP-like induction, or have high-risk features (eg, MIPI-high or blastoid/pleomorphic MCL) may benefit most from autologous hematopoietic cell transplantation consolidation,&rdquo; the investigators wrote.

Propensity score—weighted analysis was performed on 1003 of the patients, which also showed a significant improvement in PFS with AHCT, with a median PFS of 78.0 months with AHCT versus 48.5 months without (HR, 0.70; 95% CI, 0.59-0.84;P<.05). The analysis did not show a statistically significant improvement in OS though. The median OS was 147 with AHCT versus 138 months without (HR, 0.87; 95% CI, 0.69-1.10;P= .24).

&ldquo;To reduce inherent biases of retrospective analyses, we elected to perform a propensity score—weighted analysis and demonstrated persistence of the observed improvement in progression-free survival. In contrast, although improved overall survival was observed on unadjusted analysis, this improvement did not persist for the entire cohort after propensity score&ndash;weighted analysis, raising the possibility that any observed benefits may have resulted from confounding.&rdquo;

Among the patients that did not undergo AHCT, 34% progressed, and 29% of these patients then received transplantation in the second-line.

Seven patients (1.2%) who underwent AHCT died within 100 days of transplantation. Two percent developed a secondary blood cancer, but there was no difference in the rate between the group that received AHCT and among the patients who did not.

&ldquo;With this and other well-designed prospective trials as well as with well-validated predictive biomarkers, clinicians will be better able to provide a more refined, risk-adapted approach to first-line management of mantle cell lymphoma,&rdquo; the study authors concluded.

Reference:

Gerson JN, Handorf E, Villa D, et al. Survival outcomes of younger patients with mantle cell lymphoma treated in the rituximab era [published online January 7, 2019].J Clin Oncol.doi: 10.1200/JCO.18.00690.