The introduction of novel agents in the management of
multiple myeloma and related
plasma cell dyscrasias has changed our treatment approaches and subsequently the outcome of patients. Due to current advances, the European Myeloma Network updated the diagnostic and therapeutic recommendations for patients with Waldenström's
macroglobulinemia (WM),
AL-amyloidosis,
monoclonal immunoglobulin deposition disease (MIDD),
POEMS syndrome, and primary
plasma cell leukemia. For patients with WM, the combination of
rituximab with
chemotherapy remains the treatment cornerstone, while the
Bruton-tyrosine kinase inhibitor
ibrutinib has been introduced and approved for relapsed/refractory disease. The management of light chain
amyloidosis depends on the presence and severity of heart disfunction. If present, intensification with an autologous
stem cell transplantation (ASCT) is not recommended. Further aggregation of misfolded light chains could be prevented by
doxycycline or
monoclonal antibodies targeting
amyloid deposits. Initial treatment generally consists of
melphalan/
dexamethasone or
bortezomib-based regimens. For relapsing patients, one can consider
proteasome inhibitors,
immunomodulatory agents,
melphalan or
daratumumab. Because intact or
light-chain immunoglobulins are also the culprits for MIDD, the small monoclonal plasma cells' clones should be treated and generally respond well to
bortezomib-based treatment.
POEMS syndrome is a well-defined clinical entity that can present as solitary bone lesions or disseminated disease.
Radiation therapy is used for patients with localized disease and result in long-lasting response. Systemic treatment should be proposed to patients with disseminated disease, but regimens that can worsen a pre-existing
polyneuropathy should be avoided. PPCL is located at the other end of the spectrum of plasma cell disorders and is associated with an aggressive disease course and poor prognosis. It requires an imminent, multi-phase and novel agents-based
therapy, including induction, ASCT, consolidation and maintenance, with short treatment-free intervals. Patients not eligible for transplant procedures require personalized, intensive therapeutic approach. Allogeneic
stem cell transplantation can be used in selected patients.