Real-Life Multicentre Study on 547 Patients Affected By Waldenstrom Macroglobulinemia Treated with Chemo-Immunotherapy: Which Is the Best and Most Used First-Line Treatment?

Waldenström Macroglobulinaemia (WM) is an indolent lymphoma still primarily managed with chemo-immunotherapy, which remains a key first-line treatment option, although recently BTKIs have emerged as potential therapies for untreated patients.

The aim of our study was to evaluate and compare efficacy and safety of different chemo-immunotherapeutic regimens commonly used in Italy for frontline WM treatment.

A retrospective analysis was conducted on 547WM patients enrolled between 2008-2022 from 14 Italian haematological centres. Among them, 245 received the BR scheme (bendamustine-rituximab), 116 were treated with DRC (dexamethasone-rituximab-cyclophosphamide), and 129 were treated with various other regimens including monotherapy with chlorambucil or cyclophosphamide as well as more aggressive combinations, such as Chl-R (chlorambucil-rituximab), FCR (fludarabine-cyclophosphamide-rituximab) or R-CHOP (rituximab-cyclophosphamide-doxorubicin-vincristine-prednisone), 48 patients received rituximab monotherapy for neurological symptoms.

The main focus of our analysis was on the two major treatment groups: BR and DRC.

There were notable differences between these two groups in terms of age at treatment (69 vs 70 years old, respectively), CIRS (more patients with CIRS>6 in DRC) and revised IPSSWD (higher risk rates in BR). Patients treated with BR tended to be younger, more fit but also had a more aggressive disease.

Overall survival (OS) curves did not show significant differences between the two schemes (5-year OS 87.5% for BR and 93.0% for DRC, p=0.42). Similarly, the analysis of progression free survival (PFS) curves demonstrated a better PFS at 5 years for BR (79.2%) compared to DRC (54.5%) (p<0.001; figure 1A). The median PFS was 63.6 months for DRC, while it was not reached for BR. When analysing BR–treated patients separately (standard dose and reduced initial dose) both groups showed better PFS curves than DRC (p<0.001; figure 1B).

Multivariate analysis identified the choice of the treatment (BR vs DRC) as the sole significant variable impacting PFS (RR 1.76).

Notably, approximately 33% of the patients treated with BR received an initial bendamustine dose lower than the standard dose of 90 mg/m² for first-line therapy with 91% of these cases receiving 70 mg/m². The two schemes BR and DRC were well tolerated with no significant reduction in administered cycles (16.3% for BR vs 20.7% for DRC). However, dose reduction was more common for BR (14.3%) compared to DRC (6.0%).

In conclusion, this large Italian retrospective real-life study showed excellent outcomes for unselected WM patients treated with chemo-immunotherapy. Despite the emergence of new treatment options, chemo-immunotherapy remains a highly effective treatment modality for these patients. The long-term follow-up confirmed better PFS for BR-treated patients, while OS, remained comparable between BR and DRC. Moreover, the BR scheme exhibited excellent PFS even with a reduced initial bendamustine dose.