Daratumumab–bortezomib–dexamethasone use in relapsed POEMS syndrome

Abstract

POEMS syndrome is a rareparaneoplastic disorder driven by an underlying low level plasma cell dyscrasiaand associated with elevated serum vascular endothelial growth factor (VEGF). Dueto its rarity, there are no internationally agreed standards of care, with verylimited data to guide management in the relapse setting. Agents used in myelomaare rational choices and have been employed. Daratumumab has been reported intwo case studies with lenalidomide-dexamethasone, one in the upfront and one inthe relapsed setting. We are the first to report here three cases ofdaratumumabbortezomib-dexamethasone (DVd) use in relapsed POEMS postautologous stem cell transplant with good VEGF and clinical responses. Our casesadd to the literature on efficacy of daratumumab and are the first to report onits safe use with bortezomib in relapsed POEMS. It should be considered as aclinical option, in patients not responding to conventional first linetherapies.

Evidence‐based medical treatment of POEMS syndrome

“…The anti‐CD38 monoclonal antibody daratumumab is another attractive option, but currently has been limited to case reports, with one case reporting success employing daratumumab–lenalidomide–dexamethasone in the up‐front setting 40 . The largest series reports three cases of daratumumab–bortezomib–dexamethasone post‐ASCT with clinical and VEGF responses 41 . Anti‐B‐cell maturation antigen (BCMA) chimaeric antigen receptor (CAR) T‐cell immunotherapy has been used to good effect in a single patient with concomitant myeloma 42 …”

“…40 The largest series reports three cases of daratumumab-bortezomib-dexamethasone post-ASCT with clinical and VEGF responses. 41 Anti-B-cell maturation antigen (BCMA) chimaeric antigen receptor (CAR) T-cell immunotherapy has been used to good effect in a single patient with concomitant myeloma. 42 VEGF inhibitors such as bevacizumab are theoretically an appealing option but have shown only mixed responses, and in some cases have been associated with rapid clinical deterioration, multi-organ failure and death, [43][44][45] so are not recommended.…”

Comprehensive Diagnosis and Management of POEMS Syndrome

“…The anti-CD38 monoclonal antibody, daratumumab, is another attractive option, but with limited data to support its use. 45 …”

“…The anti-CD38 monoclonal antibody, daratumumab, is another attractive option, but with limited data to support its use. 45 VEGF inhibitors such as bevacizumab have a theoretical rationale, but been associated with increased mortality and are not used. 46 Some patients reach a diagnosis of POEMS via the Castleman disease route with biopsy-proven evidence of Castleman disease and usually little or no neuropathy.…”

Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal gammopathy and Skin abnormalities (POEMS) Syndrome in a Filipino Nurse Returning to Work Following Bortezomib Treatment: A Case Report

“…Thus, utilization of bortezomib as frontline monotherapy appears to be tolerated and highly effective. [2] In relapse cases, other treatment options were tested in which the combination of bortezomib and dexamethasone was given together with daratumumab, an immunomodulatory drug [3] or cyclophosphamide. On the other hand, other publications reported the use of bortezomib and dexamethasone only as a first-line regimen for newly diagnosed POEMS syndrome and a majority of these patients include Chinese males in their fifth decade of life.…”