James N. Gerson, MD
Within 6 months of receiving induction chemotherapy, consolidation treatment with autologous hematopoietic cell transplantation (AHCT) correlated with a significant improvement in progression-free survival (PFS) in younger, fit patients with mantle cell lymphoma (MCL), according to a retrospective analysis published in the Journal of Clinical Oncology
However, in a propensity score–weighted (PSW) analysis, overall survival (OS) was not improved with consolidation AHCT.
“MCL remains an incurable lymphoma with no clearly defined standard-of-care first-line treatment strategy,” first study author James N. Gerson, MD, Fox Chase Cancer Center, and coinvestigators wrote. “In this large retrospective cohort of younger, transplantation-eligible patients with MCL who achieved a partial response (PR) or better after induction chemotherapy, we demonstrated improved PFS for patients who underwent consolidative AHCT.”
Data from 25 North American academic centers were collected on 1254 patients. Eligible patients were aged ≤65 years, newly diagnosed, and transplant eligible at the time of diagnosis. Patients had to have received induction therapy between 2000 and 2015 and achieved a PR or better. AHCT was defined as transplant within 6 months of induction therapy. Additionally, the primary endpoint of the study was PFS, with a secondary endpoint of OS.
Patients were excluded if they were aged >65 years (n = 27), received radiation therapy alone, failed to achieve a PR or better to induction therapy (n = 74), were ineligible for transplant, received consolidative allogeneic transplant (n = 47), or had insufficient data available (n = 44).
Evaluable patients were further divided by cyclin D1 positivity (n = 915; 89%), Ki-67 expression (43%), and blastoid or pleomorphic morphology (n = 136; 13%). Most patients (n = 973; 95%) received an anti-CD20 monoclonal antibody as part of their induction treatment, whereas only 2.5% (n = 26) received a novel therapy as part of induction therapy. Thirty percent of patients (n = 306) received maintenance rituximab (Rituxan). Patients were otherwise balanced in terms of prognostic factors, tumor characteristics, and treatment regimens.
Of 1029 eligible patients, 64% (n = 657) went on to receive AHCT consolidation after induction. The remaining 372 patients did not undergo transplant due to physician choice, (n = 249; 67%), patient preference (n = 66; 18%), unspecified (n = 45; 12%), and other reason (n = 12; 3%).
The median age at the time of diagnosis was 57 years. 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%.
At a median follow-up of 76 months, the median PFS and OS were 62 months and 139 months, respectively. Multivariable regression analysis (MVA) revealed an improvement in PFS (HR, 0.54; 95% CI, 0.44-0.66; P
<.01) and a trend toward improved OS (HR, 0.77; 95% CI, 0.59-1.01; P
= .06) with AHCT consolidation versus no consolidative transplant. With the PSW analysis, the PFS benefit was maintained (HR, 0.70; 95% CI, 0.59-0.84; P
<.05). However, it failed to demonstrate an improvement in OS (HR, 0.87; 95% CI, 0.69-1.1; P
Improved PFS with consolidative AHCT was observed irrespective of patient subgroups. Although the observed benefit with OS was lost after controlling for outstanding covariates, select high-risk patients and those who did not receive cytarabine as part of induction or intensive induction appeared to still benefit. Moreover, improved OS was noted in patients with high-risk Mantle Cell Lymphoma International Prognostic Index scores, those who received a CHOP-like induction therapy, and those with blastoid or pleomorphic variants.
Regarding safety, 1.2% (n = 7) of patients who underwent consolidative AHCT died within the first 100 days of transplant. At a median follow-up of 76.8 months, 2% (n = 21) of patients presented with secondary myelodysplastic syndrome or acute myeloid leukemia.
Gerson et al noted that the findings of this retrospective study demonstrated positive data supporting the use of AHCT consolidation following induction for favorable-risk patients, warranting prospective randomized trials to confirm the PFS benefit observed in this study population.
However, for patients who achieve minimal residual disease (MRD) negativity following induction, AHCT consolidation may not be necessary. In the ongoing phase III EA4151 trial (NCT03267433), patients with MCL who are MRD negative upon entering into a complete remission will be randomized to rituximab with or without AHCT.
“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 MCL,” concluded Gerson et al.
Gerson J, Handorf E, Villa D, et al. Survival outcomes of younger patients with mantle cell lymphoma treated in the rituximab era. [published online ahead of print January 7, 2019]. J Clin Oncol. doi: 10.1200/JCO.18.00690.