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Daratumumab for POEMS Syndrome

      To the Editor:
      The syndrome of polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes (POEMS) is a rare disorder. It is considered paraneoplastic to a usually IgAλ-secreting monoclonal plasma cell dyscrasia.
      • Dispenzieri A.
      POEMS syndrome: 2017 update on diagnosis, risk stratification, and management.
      High-dose melphalan followed by autologous stem cell transplant (ASCT) is the standard of care in disseminated POEMS syndrome but can be associated with significant treatment-related morbidity and mortality.
      • Dispenzieri A.
      • Moreno-Aspitia A.
      • Suarez G.A.
      • et al.
      Peripheral blood stem cell transplantation in 16 patients with POEMS syndrome, and a review of the literature.
      No paradigm exists for managing patients who experience relapse and those ineligible for ASCT. Herein, we report the first case of POEMS syndrome treated successfully with the anti-CD38 monoclonal antibody daratumumab and lenalidomide.

      Report of Case

      A 60-year-old woman presented with a progressive sensorimotor polyneuropathy, weight loss, and acrocyanosis of the distal extremities and nose. Laboratory evaluation revealed an IgAλ monoclonal band of 0.7 g/dL and elevated serum IgA (689 mg/dL). The λ and κ free light chain levels were 10.3 mg/dL and 3.7 mg/dL, respectively (Supplemental Table, available online at http://www.mayoclinicproceedings.org). Bone marrow biopsy studies revealed 5% to 10% plasma cells with 0.59% myelomatous cells. The vascular endothelial growth factor (VEGF) level was 2222 pg/mL, and the platelet count was 572 × 109/L. Imaging identified no bone disease or organomegaly. POEMS syndrome was diagnosed. Prior treatment with intravenous immunoglobulin and oral prednisone had yielded no response. The patient underwent ASCT with reduced-dose melphalan (140 mg/m2) because of her poor performance status. A rapid reduction in VEGF, IgA, and marrow plasma cell infiltration and gradual clinical improvement ensued (Figure).
      Figure thumbnail gr1
      FigureThe percentage of myelomatous plasma cells by 8-color flow cytometry, serum levels of vascular endothelial growth factor, and serum levels of β2-microglobulin shown according to time, treatment modality, and response. VEFG = vascular endothelial growth factor.
      However, 18 months posttransplant, the patient again experienced acrocyanosis, peripheral edema, fatigue, weight loss, and neurologic deterioration. Disease recurrence was preceded by serially increasing VEGF, β2-microglobulin, and IgA levels and reappearance of frank myelomatous plasma cells in the bone marrow. Lenalidomide (15 mg, days 1-21 and 28), ixazomib (4 mg, days 1, 8, and 15), and dexamethasone (20 mg weekly) were administered for 1 month as salvage therapy without improvement. Treatment was switched to lenalidomide (15 mg through days 1 to 21) and daratumumab (16 mg/kg weekly by intravenous infusion for 8 doses), with dexamethasone for infusion reaction prophylaxis. After 8 weekly doses of daratumumab, she received an additional 8 doses every other week before switching to monthly daratumumab. Normalization of the λ and κ free light chain levels, reduction of M component to zero, and bone marrow morphology negative for myelomatous cells was achieved. Eleven months after starting salvage therapy, her response was ongoing; she could walk unaided despite bilateral foot drop, and she had regained fine motor skills, allowing her to resume work as an accountant.

      Discussion

      We speculate that in our patient the reduction in melphalan dose from 200 mg/m2 to 140 mg/m2 allowed clonal plasma cells to survive. The well-documented efficacy of daratumumab plus lenalidomide in relapsed multiple myeloma
      • Dimopoulos M.A.
      • Oriol A.
      • Nahi H.
      • et al.
      POLLUX Investigators
      Daratumumab, lenalidomide, and dexamethasone for multiple myeloma.
      • Plesner T.
      • Arkenau H.T.
      • Gimsing P.
      • et al.
      Phase 1/2 study of daratumumab, lenalidomide, and dexamethasone for relapsed multiple myeloma.
      prompted us to treat our patient in a similar fashion. Responses to daratumumab in AL (immunoglobulin light chain) amyloidosis have also been reported.
      • Sher T.
      • Fenton B.
      • Akhtar A.
      • Gertz M.A.
      First report of safety and efficacy of daratumumab in 2 cases of advanced immunoglobulin light chain amyloidosis.
      In our patient with POEMS syndrome, the remarkable response to daratumumab and lenalidomide suggests that this combination is a promising nontoxic alternative to ASCT that warrants exploration in POEMS syndrome.

      Supplemental Online Material

      Supplemental material can be found online at: http://www.mayoclinicproceedings.org. Supplemental material attached to journal articles has not been edited, and the authors take responsibility for the accuracy of all data.

      References

        • Dispenzieri A.
        POEMS syndrome: 2017 update on diagnosis, risk stratification, and management.
        Am J Hematol. 2017; 92: 814-829
        • Dispenzieri A.
        • Moreno-Aspitia A.
        • Suarez G.A.
        • et al.
        Peripheral blood stem cell transplantation in 16 patients with POEMS syndrome, and a review of the literature.
        Blood. 2004; 104: 3400-3407
        • Dimopoulos M.A.
        • Oriol A.
        • Nahi H.
        • et al.
        • POLLUX Investigators
        Daratumumab, lenalidomide, and dexamethasone for multiple myeloma.
        N Engl J Med. 2016; 375: 1319-1331
        • Plesner T.
        • Arkenau H.T.
        • Gimsing P.
        • et al.
        Phase 1/2 study of daratumumab, lenalidomide, and dexamethasone for relapsed multiple myeloma.
        Blood. 2016; 128: 1821-1828
        • Sher T.
        • Fenton B.
        • Akhtar A.
        • Gertz M.A.
        First report of safety and efficacy of daratumumab in 2 cases of advanced immunoglobulin light chain amyloidosis.
        Blood. 2016; 128: 1987-1989