Author Response: Obinutuzumab, a potent anti–B-cell agent, for rituximab-unresponsive IgM anti-MAG neuropathy
Marinos C.Dalakas, Professor of Neurology, Thomas Jefferson University Philadelphia, PA and National and Kapodistrian University of Athens Medical School, Athens Greece
UbaldoMartinez-Outschoorn, Associate Professor, Thomas Jefferson University Philadelphia, PA
GoranRakocevic, Associate Professor, Thomas Jefferson University Philadelphia, PA
Submitted May 04, 2018
The therapeutic response reported by Briani et al. in two patients with anti-MAG neuropathy after treatment with the combination of chlorambucil and obinutuzumab is certainly of interest. These patients however had chronic lymphocytic leukemia (CLL) and their neuropathy was paraneoplastic and very likely not chronic. In contrast, our patients had benign IgM monoclonal gammopathy and long-lasting neuropathy, as commonly seen in most cases of anti-MAG neuropathy. It is also unclear if the described response was strictly related to obinutuzumab or to the combination with chlorambucil, especially since we know that chlolrorambucil alone can improve anti-MAG neuropathy associated with lymphoid malignancies [1]. It is not unexpected to see improvement of the patients’ neuropathy if the underlying malignancy is successfully treated early in the disease course.
The observation, however, that chlorambucil combined with obinutuzumab can help anti-MAG neuropathy in CLL patients is not necessarily applicable to patients with benign IgM gammopathy. Chlorambucil administration in CLL has now substantially decreased with the advent of more effective and less toxic therapies [2]. The suggestion, therefore, to apply from the outset the potentially toxic combination of chlorambucil and obinutuzumab in neuropathy patients with benign gammopathy requires significant caution.
References
1. Dalakas MC, Flaum MA, Rick M, Engel WK, Gralnick HR. Treatment of polyneuropathy in Waldenstrom’s macroglobulinemia. Role of paraproteinemia and immunological studies. Neurology 1983;33:1406-1410.
2. Lamanna N, O'Brien S. Novel agents in chronic lymphocytic leukemia. Hematology Am Soc Hematol Educ Program. 2016;2016:137-145.
The therapeutic response reported by Briani et al. in two patients with anti-MAG neuropathy after treatment with the combination of chlorambucil and obinutuzumab is certainly of interest. These patients however had chronic lymphocytic leukemia (CLL) and their neuropathy was paraneoplastic and very likely not chronic. In contrast, our patients had benign IgM monoclonal gammopathy and long-lasting neuropathy, as commonly seen in most cases of anti-MAG neuropathy. It is also unclear if the described response was strictly related to obinutuzumab or to the combination with chlorambucil, especially since we know that chlolrorambucil alone can improve anti-MAG neuropathy associated with lymphoid malignancies [1]. It is not unexpected to see improvement of the patients’ neuropathy if the underlying malignancy is successfully treated early in the disease course.
The observation, however, that chlorambucil combined with obinutuzumab can help anti-MAG neuropathy in CLL patients is not necessarily applicable to patients with benign IgM gammopathy. Chlorambucil administration in CLL has now substantially decreased with the advent of more effective and less toxic therapies [2]. The suggestion, therefore, to apply from the outset the potentially toxic combination of chlorambucil and obinutuzumab in neuropathy patients with benign gammopathy requires significant caution.
References
1. Dalakas MC, Flaum MA, Rick M, Engel WK, Gralnick HR. Treatment of polyneuropathy in Waldenstrom’s macroglobulinemia. Role of paraproteinemia and immunological studies. Neurology 1983;33:1406-1410.
2. Lamanna N, O'Brien S. Novel agents in chronic lymphocytic leukemia. Hematology Am Soc Hematol Educ Program. 2016;2016:137-145.