San Diego, California—Induction chemotherapy followed by bortezomib maintenance (BM) or consolidation (BC) was efficacious and tolerable for patients with mantle cell lymphoma (MCL) who underwent autologous stem cell transplant (ASCT), according to an 8-year follow-up of the CALGB 50403 trial.

These findings were presented by Lawrence Kaplan, MD, Helen Diller family Comprehensive Cancer Center, University of California, San Francisco, at the 2018 ASH Annual Meeting.

Interim results from CALGB50403 demonstrating a 5-year progression-free survival (PFS) of 70% for patients receiving BM and 69% for those receiving BC were previously presented at the 2015 ASH Annual Meeting. Dr Kaplan and colleagues compared outcomes from the CALGB 50403 trial to those from CALGB 59909, which only differed from CALGB 50403 by the absence of post-transplant bortezomib.

Induction therapy was with 2-3 cycles of augmented R-CHOP and methotrexate followed by high-dose cytarabine/etoposide/rituximab/filgrastim stem cell mobilization and cyclophosphamide/carmustine/etoposide ASCT. Patients were randomized to BC (1.3 mg/ m2 IV days 1, 4, 8, 11 of a 3-week cycle for 4 cycles) or BM (1.6 mg/m2 IV weekly x4 every 8 weeks for 18 months) after two doses of post-transplant rituximab.

Minimal residual disease (MRD) was analyzed using patient-specific PCR probes for the bcl-1/IgH junction or the IgH CDR3 region. The primary endpoint was PFS measured from randomization for each trial arm.

A total of 151 patients were enrolled between October 2006 and June 2010, of which 147 received treatment and were included in the analysis. 118 patients underwent ASCT and 102 were randomized, 52 to BM and 50 to BC. Following randomization, 34 patients completed BM and 33 completed BC.

A total of 45 patients withdrew from treatment. Most withdrawals were for disease progression or adverse events, including 4 treatment-related deaths. Withdrawal from adverse events occurred in 14 patients in the BM arm and 7 patients in the BC arm, primarily for cytopenias or peripheral neuropathy.

At a median follow-up of 7.8 years from randomization, median PFS was not reached for the BM arm and was 8.9 years for the BC arm. The 8-year PFS estimates in the BM and BC arms were 77% and 58%, respectively.

The 8-year PFS from the time of registration was 43.6% among all 147 patients treated on CALGB 50403. PFS from registration was not significantly extended in CALGB 50403 compared to CALGB 59909 but was significantly extended from the time of transplant. Baseline patient characteristics were not significantly different between the two trials.

The 8-year PFS from registration in CALGB 50403 was 52.0% in MIPI low risk, 37.5% in intermediate risk, and 28.2% in high-risk. Bone marrow MRD results were collected for a total of 42 patients post-induction therapy. The 8-year PFS estimates were 80.2% (n=17) and 43.2% (n=25) for MRD-negative and MRD-positive patients, respectively (p=0.009).

“Induction chemotherapy followed by ASCT and either BC or BM was efficacious and tolerable, although BC was associated with more withdrawals for toxicity. The comparison between studies 50403 and 59909 with long-term follow up continues to suggest a PFS benefit from the addition of BC or BM among patients undergoing transplant,” Dr Kaplan and colleagues concluded.

“MRD-negativity following induction chemo-immunotherapy is highly associated with improved PFS and the role of ASCT in post-induction MRD-negative patients is currently under investigation in a randomized clinical trial,” they added.

Kaplan LD,  Maurer MJ, Stock W, et al. Bortezomib Maintenance (BM) or Consolidation (BC) Following Aggressive Immunochemotherapy and Autologous Stem Cell Transplant (ASCT) for Untreated Mantle Cell Lymphoma (MCL): 8 Year Follow up of CALGB 50403 (Alliance) Presented at: the 60th ASH Annual Meeting and Exposition; December 1-4, 2018; San Diego, CA. Abstract 146.