DISCUSSION
In the cases reported in the literature, there is a high rate of
hematological and clinical responses to ASCT treatment with some
patients responding only to the second ASCT[13, 28]. The clinical
case we present initiated treatment 14 months after disease onset and
did not achieve a good response after ASCT, showing some intensification
of the myopathy after transplant followed by a stabilization and later
slight improvement in autonomy in the daily life activities.
The most significant revision of transplanted SLONM-MGUS patients
identified, as predictors of inadequate response to ASCT, the long
course of the disease before the hematological treatment and the
persistence of gammopathy after treatment[28], which were present in
our clinical case. Furthermore, the increase of the M protein level
precedes clinical deterioration, and there is a correlation between
clinical course and amount of protein detected in peripheral blood[11,
28]. Age at onset, light chain type of the monoclonal protein (kappa
vs lambda) and severity of muscle weakness are not associated with a
specific outcome[28].
Delayed ASCT may have affected response to treatment. However, according
to these data which suggests a correlation between clinical course and
gammopathy response, the goal of treatment should always be a complete
response with suppression of the neoplastic clone, as soon as possible,
to reduce the monoclonal protein and its toxic effects. Efficacy of
Chemotherapy toward plasma cell dyscrasia without stem-cell
transplantation has been reported as well[13]. In order to deepen
hematological response to achieve a parallel clinical improvement,
patients should receive additional Chemotherapy targeting plasma cell
clone. Our clinical case illustrates the importance of implementing
several treatments, such as proteasome inhibitors and immunomodulators,
to obtain a complete hematologic response and consequently, the best
clinical improvement. The complete hematologic response was achieved
with the third line of treatment, allowing stabilization of muscle
weakness and an impressive recovery of body weight. This approach
supports the rationale of treating the monoclonal gammopathy to get the
best neurological symptoms response [19, 20, 26, 28]. Whether or not
nemaline rods diminished in our patient with treatment is not known, as
a muscle biopsy was not performed after clinical improvement.
This clinical case shows that proteasome inhibitors and immunomodulators
might be an effective therapy of SLONM related to monoclonal gammopathy
in cases without a good response to ASCT or for patients with
comorbidities who are not eligible for ASCT.
Even though the nature of the relationship between SLONM and monoclonal
gammopathy is not entirely clarified, the correlation between clinical
response and hematological response suggests a direct association
between M protein and the disorder[13, 14]. All of these data have
transformed SLONM associated with monoclonal gammopathy in a treatable
disease with therapy directed toward plasma cell dyscrasia rather than
immunosuppressive drugs used in autoimmune diseases[14]. The goal to
eradicate clonal plasma cells, similar to other plasma cell dyscrasias
makes logical the proposition to classify SLONM associated with
monoclonal gammopathy as a monoclonal gammopathy with neurological
significance (MGNS) and as a plasma cell dyscrasia with toxic monoclonal
protein, similar to AL amyloidosis or POEMS [13, 28].