San Diego, California—Induction therapy with rituximab/bendamustine (RB) and rituximab/cytarabine (RC) followed by autologous stem cell transplantation (ASCT) resulted in high rates of durable remissions for patients with mantle cell lymphoma (MCL), according to results from two phase 2 trials presented by Reid W. Merryman, MD, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, and colleagues at the 2018 ASH Annual Meeting.

“Induction chemoimmunotherapy followed by autologous stem cell transplantation (ASCT) is a standard of care for transplant eligible patients with untreated mantle cell lymphoma (MCL); however, there is no consensus on the optimal induction regimen,” explained Dr Merryman and colleagues.

The addition of RC to an RCHOP-like regimen has been associated with better outcomes and two randomized trials have demonstrated superior efficacy and tolerability for RB compared to RCHOP for patients with untreated MCL.

Based on this, Dr Merryman and colleagues conducted a phase 2 trial examining RB followed by RC for transplant eligible patients with untreated MCL (DFCI trial). Simultaneously, investigators at Washington University in St. Louis initiated a similar study of alternating cycles of RB/RC for untreated MCL (WUSTL trial).

In the DFCI trial, treatment eligible patients with untreated MCL were treated with 3 cycles of RB (rituximab, 375 mg/m2 on day 1; bendamustine, 90 mg/m2 on day 1-2) followed by 3 cycles of RC (rituximab, 375 mg/m2 on day 1; cytarabine, 3gm/m2 BID on day 1-2 with dose reductions for age, renal dysfunction, or pre-existing neurotoxicity). Clinical and pharmacy databases were used to identify off-trial patients receiving this regimen. In the WUSTL trial, treatment eligible patients received alternating cycles of RB (cycles 1, 3, 5) and RC (cycles 2, 4, 6).

A total of 86 patients were treated with RB/RC and 84% completed 6 cycles of therapy. Off-trial patients were more likely to receive a lower starting dose (≤ 2gm/m2) of cytarabine compared to trial patients.

At the end of induction, the overall response rate and CRR were 98% and 92%, respectively. A total of 73 patients (85%) subsequently underwent ASCT and 4 additional patients are scheduled to undergo ASCT. Nine patients did not undergo ASCT because of persistent or progressive disease (n=3), prolonged cytopenias (n=3), an incidentally identified ASXL1 mutation without cytopenias (n=1), patient preference (n=1), and inadequate stem cell collection (n=1).

Delayed platelet engraftment after ASCT was seen for pts receiving alternating cycles of RB/RC compared to sequential RB/RC at day 30 (plts <50: 70% vs 16%, p=0.001) and at day 100 (plts <100: 60% vs 21%, p=0.017). An initial cytarabine dose >2gm/m2 was also associated with reduced 30-day platelet count (plts <50: 41% vs 8%, p=0.004).

Dr Merryman and colleagues noted that there was 1 treatment-related death from respiratory failure and respiratory syncytial virus infection (Day 56 after ASCT).

The median follow-up was 32 months among survivors overall (54m for DFCI trial, 28m for DFCI off-trial, 19m for WUSTL trial). PFS for the entire cohort at 24 and 48 months were 88% and 80%, respectively, and OS were 96% and 92%, respectively. In univariate analyses, a higher cytarabine dose (>2gm/m2) was not associated with improved PFS, while blastoid or pleomorphic variant (HR 4.5, p=0.016) and high-risk MIPI score (HR 4.0, p=0.034) were both associated with inferior PFS.

“Induction therapy with RB/RC followed by ASCT achieved high rates of durable remissions in two phase 2 clinical trials,” Dr Merryman and colleagues concluded.

“RB/RC is therefore an excellent choice of induction therapy for treatment eligible patients with untreated MCL and could be further tested in comparative prospective trials. Sequential, rather than alternating, RB/RC cycles and lower dose cytarabine may reduce the risk of prolonged thrombocytopenia post-ASCT,” they added.—Janelle Bradley

Merryman RW, Kahl BS, Redd RA, et al. Rituximab/Bendamustine and Rituximab/Cytarabine (RB/RC) Induction Chemotherapy for Transplant-Eligible Patients with Mantle Cell Lymphoma: A Pooled Analysis of Two Phase 2 Clinical Trials and Off-Trial Experience. Presented at: the 60th ASH Annual Meeting and Exposition; December 1-4, 2018; San Diego, California. Abstract 145.