Alternating R-DA-EDOCH/R-DHAP induces deep remission in young Chinese patients with MCL

A phase III trial demonstrated a high minimal residual disease (MRD)-negativity rate with intensive continuous dose-adjusted rituximab plus etoposide, dexamethasone, doxorubicin, cyclophosphamide, and vincristine (R-DA-EDOCH) alternated with rituximab, dexamethasone, cytarabine, and cisplatin (R-DHAP), thereby offering an alternative induction therapy choice for young Chinese patients with mantle-cell lymphoma (MCL).

Published data indicate that compared with their Western counterparts, Chinese patients with MCL tend to be younger and have a higher prevalence of TP53 deletion and MYC abnormalities, which are associated with poor prognosis and suggest enhanced tumour cell proliferation in this population. [Oncotarget 2015;6:42362-71] “Given the efficacy and tolerability of the dose-enhanced immunochemotherapy R-DA-EDOCH regimen in patients with multiple high-risk aggressive B-cell lymphomas and the potentially elevated tumour cell activity in Chinese patients, we designed alternating R-DA-EDOCH/R-DHAP induction therapy as an augmented version of the RCHOP/R-DHAP regimen for young patients with newly diagnosed MCL,” wrote the investigators. [J Clin Oncol 2019;37:1790-1799; Cancer Biol Med 2025;22:177-189]

A total of 55 patients (age range, 37–65 years; median age, 53 years; male, 69.1 percent) with newly diagnosed MCL were enrolled. Almost all patients (94.6 percent) had advanced-stage disease (Ann Arbor stage III–IV) and 38.2 percent presented with B symptoms. TP53 mutation results were available in 42 patients, showing a mutation frequency of 26.2 percent. Other molecular findings included MYC rearrangements/amplifications in 30.0 percent, 17p deletions in 18.9 percent, and 9p deletions in 34.1 percent of patients. Notably, 16.7 percent of patients had both TP53 mutations and 17p deletion. Immunoglobulin heavy-chain variable region (IGHV) somatic hypermutation analysis was performed in 33 patients, 66.7 percent of whom had unmutated IGHV genes. Overall, 61.8 percent of patients were identified as having at least one high-risk factor according to risk stratification, pathological classification, and molecular genetic abnormalities.

All patients received at least two cycles of alternating R-DA-EDOCH/R-DHAP immunochemotherapy and completed an efficacy and safety evaluation. At the end of induction (EOI), 98.1 percent of patients achieved objective response, with a complete response rate (CRR) or 89.1 percent. No significant differences were observed in CRR and objective response rate across subgroups with various prognostic characteristics, such as MCL International Prognostic Index (MIPI), combined MIPI (MIPI-c), pathological traits, copy number variations, and crucial tumour suppressor gene mutations.

Of the 55 patients, 48 had bone marrow involvement at initial diagnosis. Of these, 68.8 percent underwent bone marrow evaluation after two treatment cycles, with this proportion reaching 93.8 percent after four treatment cycles, and finally increasing to 95.8 percent at EOI. A notable majority of patients quickly reached MRD-negative status. Specifically, the MRD-negativity rates were 51.5 percent after two treatment cycles, 93.3 percent after four cycles, and 95.7 percent at EOI. “Impressively, by EOI, no detectable MRD was observed among any of the patients who achieved CR [n=49]. Additionally, of the five patients with partial response, MRD was undetectable in the bone marrow of three patients,” highlighted the investigators.

The alternating R-DA-EDOCH/R-DHAP regimen was well tolerated; no patients discontinued treatment because of intolerable treatment-related adverse events (AEs). Most patients (85.5 percent) experienced at least one haematologic AE. Grade 3–4 leukopenia and neutropenia were reported in 49.1 and 58.2 percent of patients, respectively, and 14.5 percent experienced grade 3 neutropenic fever. There were no grade 4 nonhaematologic AEs. The most common nonhaematologic AEs were grade 1–2 nausea/vomiting (25.4 percent), fatigue (17.9 percent), and peripheral neuritis (14.5 percent).