Bendamustine-Rituximab Combination for Immuno-Mediated Neuropathies

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Combination of bendamustine with rituximab treatment may be an effective regimen for immune-mediated neuropathies associated with hematologic malignancy.

Combination of bendamustine with rituximab (BR) treatment may be an effective regimen for immune-mediated neuropathies associated with hematologic malignancy, according to a case-series published in the Journal of the Neurological Sciences.

Hematologic malignancy may be associated with chronic polyneuropathies and previous studies have shown that anti-myelin-associated glycoprotein antibody-neuropathy is the paradigm of paraproteinemic neuropathy, but these malignancies may also be associated with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP).

The combination of rituximab and chemotherapy might be helpful in treating neuropathies, but limited data are available on the benefit of combined use of BR which is frequently used for lymphproliferative disorders. In the case-series, researchers report the long-term efficacy of 6-months combined BR treatment in 9 patients (5 women, age range 53-89 years) with inflammatory polyneuropathies associated with hematologic malignancy.

In 5 patients polyneuropathy preceded the onset of hematologic malignancy and in 4 neuropathy and malignancy were almost concomitant. Of these patients, 5 had no benefit from conventional treatment and 4 were treatment naïve. All the patients received a 6-month treatment with bendamustine 90 mg/sqm for 2 consecutive days and rituximab 375 g/sqm, every 28 days.

In all patients, BR Combination led to a complete remission of hematologic malignancy, as well as significant neurological improvement. In 6 of 9 patients a clinical improvement in neuropathy was evident as early as 2 months from beginning the combined treatment. Dramatic improvement in the disabling attitudinal and intentional tremor was reported in 2 patients and pathogenic autoantibodies significantly declined in 4 of 5 patients.

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Mean relapse free survival was 31.5 ± 12.7 months. Neurological relapses occurred in 3 patients after a mean of 38 months of sustained stability, even if hematologic malignancy remitted. All 3 patients were subsequently treated with rituximab monotherapy. The sustained response was longer with BR combination, compared to rituximab monotherapy (mean of 38 months vs. 12 months, respectively).

“Our work is the first to report the efficacy of immunochemotherapy with BR in CIDP associated with HM [hematologic malignancy] and to confirm its utility in a small series of patients with anti-MAG neuropathy,” concluded the researchers.


Massa F, Zuppa A, Pesce G, et al. Bendamustine-rituximab (BR) combined therapy for treatment of immuno-mediated neuropathies associated with hematologic malignancy [published online ahead of print, 2020 Mar 19]. J Neurol Sci. doi:10.1016/j.jns.2020.116777