Recent Advances in the Treatment and Supportive Care of POEMS Syndrome
Abstract
:1. Introduction
2. Pathogenesis of the Disease
3. Clinical Presentation and Diagnosis
4. Treatment
5. Targeting the Clone
- The role of radiotherapy
- b.
- Autologous Stem Cell Transplant (ASCT)
- c.
- Immunomodulatory Drugs (IMiDs): Lenalidomide and thalidomide therapy
- d.
- Melphalan and corticosteroid
- e.
- Bortezomib and dexamethasone
- f.
- Monoclonal Antibody Therapy
- Anti-CD38 monoclonal antibodies (Daratumumab and Isatuximab)Daratumumab combined with lenalidomide in relapsed MM was proven effective [100,101] and the responses to daratumumab in light chain amyloidosis have been well documented [102]. In patients with POEMS syndrome, the response to daratumumab and lenalidomide was remarkable as well based on case reports. This suggests that this combination is a promising less toxic alternative to ASCT that warrants further exploration in both newly diagnosed and relapsed/refractory patients [103]. Importantly, this regimen provides rapid, deep and durable responses and restores their functionality [104]. This regimen was suggested in multidrug resistant patients but needs further evaluation using prospective studies [103]. A phase II clinical trial (NCT04396496) at the University of Arkansas in the United States is currently investigating the effects of daratumumab combined with lenalidomide (up to 12 four-week cycles) with the primary objective being the outcome of neuropathy and performance status of patients. Another anti-CD38 immunotherapy isatuximab which is approved for relapsed/refractory MM may also be effective in the treatment of POEMS syndrome but its use in POEMS syndrome has not yet been reported.
- Anti-VEGF monoclonal antibody (Bevacizumab)In theory the use of bevacizumab was appealing in many cases [19,74,104,105,106,107,108]. The benefit was noticed in patients who received bevacizumab during alkylator therapy or preceding therapy [105,106]. The treatment was combined with ASCT or high dose chemotherapy [70,74] or with radiation therapy and cyclophosphamide. Clinical response and anti-VEGF response within 6 months of therapy were observed [86]. Yet, other reports where the patients were treated with bevacizumab died shortly after treatment [68,107,108]. When bevacizumab was used solely, serum VEGF decreased rapidly. However, the number of patients included in different studies was small, and a significant proportion of patients did not respond or died during treatment [108,109,110]. Due to lack of efficacy and potential for increasing mortality in some reports, bevacizumab should not be used in clinical practice for treatment of POEMS syndrome.
- Chimeric antigen receptor T (CAR-T) therapyBecause the treatments for MM were expected to be useful in many patients with POEMS, chimeric antigen receptor T (CAR-T) cells targeting B cell maturation antigen (BCMA) have been used in the treatment of relapsed and refractory multiple myeloma (RRMM) with excellent response. Recently, a report of treatment by anti-BCMA CAR-T cells in POEMS demonstrated that the treatment may be a feasible therapeutic option for patients with POEMS syndrome and RRMM who do not respond well to traditional therapies [111]. We caution against routine referral of POEMS syndrome for CAR-T therapy because the experience so far is very limited.
- Comparison of all regimensA retrospective analysis of 347 patients compared ASCT to MDex and LDex groups. ASCT was well tolerated and had the highest response and PFS rates out of all three regimens [70]. One explanation is that ASCT eradicates the underlying plasma cell clones. Yet, patients undergoing ASCT were younger with better organ function and therefore lower risk patients compared to MDex and LDex groups who were typically higher risks not eligible for ASCT. No significant difference in OS was observed between all three treatments. MDex therapy in low-risk patients achieved a response similar to that of ASCT, but that was not the case in patients categorized as medium or high-risk. LDex was highly effective in patients newly diagnosed with a similar response rate and OS as those treated with ASCT. PFS was inferior in high-risk patients even after ASCT therapy. Therefore, utilizing LDex for newly diagnosed patients is a consideration especially those who do not want ASCT or are not candidate for it [112].
6. Targeting the Symptoms of the Disease
- Peripheral neuropathy
- b.
- Targeting extravascular fluid overload
- c.
- Renal disease
- d.
- Abnormal pulmonary and heart functions
- e.
- Organomegaly
- f.
- Endocrinopathy
- g.
- Papilledema
- h.
- Sclerotic bone lesions
- i.
- Targeting skin changes
- j.
- Thrombocytosis, polycythemia, and thrombosis
7. Response Assessment
8. Prognosis of the Disease
9. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Diagnostic Criteria for POEMS Syndrome |
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Mandatory criteria (Both criteria must be satisfied) |
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Major criteria (At least one major criterion should be satisfied) |
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Minor criteria (At least one minor criterion should be satisfied) |
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Other Symptoms |
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Hematologic response | CR: Negative bone marrow/Negative immunofixation of serum and urine |
VGPR: 90% reduction in M protein or immunofixation positive only if M protein was at least 0.5 g/dL at baseline | |
PR: 50% reduction in M protein or immunofixation positive if baseline M protein was at least 1.0 g/dL | |
NR: Less than a PR | |
VEGF response | CR: Normalization of plasma VEGF <87 pg/mL |
PR: Decrease of ≥50 percent (baseline must be ≥200 pg/mL) | |
NR: Less than a PR | |
Radiologic response by FDG PET | CR: Initial FDG avidity on a baseline PET scan that disappears |
PR: Initial FDG avidity that was 50 percent improved | |
NR: Not meeting CR or PR |
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Bou Zerdan, M.; George, T.I.; Bunting, S.T.; Chaulagain, C.P. Recent Advances in the Treatment and Supportive Care of POEMS Syndrome. J. Clin. Med. 2022, 11, 7011. https://doi.org/10.3390/jcm11237011
Bou Zerdan M, George TI, Bunting ST, Chaulagain CP. Recent Advances in the Treatment and Supportive Care of POEMS Syndrome. Journal of Clinical Medicine. 2022; 11(23):7011. https://doi.org/10.3390/jcm11237011
Chicago/Turabian StyleBou Zerdan, Maroun, Tracy I. George, Silvia Tse Bunting, and Chakra P. Chaulagain. 2022. "Recent Advances in the Treatment and Supportive Care of POEMS Syndrome" Journal of Clinical Medicine 11, no. 23: 7011. https://doi.org/10.3390/jcm11237011