Abstract
Background: POEMS syndrome is a rare plasma cell disorder. The standard treatment of the disease has not been established yet. Although autologous transplantation or melphalan-based chemotherapy has significantly improved the prognosis of POEMS syndrome, however, many patients will relapse or become refractory to primary therapy. Recently, Anecdotally low dose lenalidomide (10mg, daily) and dexamethasone had good efficacy and safety for patients with refractory or relapsed POEMS syndrome. Prospective clinical data of lenalidomide for POEMS syndrome patients is lacking. We underwent a prospective phase II trial to evaluate the efficacy and safety of low dose lenalidomide and dexamethasone for newly diagnosed patients with POEMS syndrome (NCT01816620).
Methods: Patients who met the diagnostic criteria defined by Dispenzieri, with age of 18 years old or more and cytotoxic drug native, were enrolled. All patients received total 12 cycles of low dose Rdex regimen (lenalidomide 10mg/day, on 21 days of a 28-day cycle, plus oral dexamethasone 40 mg/week). Aspirin (100 mg/day) was used for thromboprophylaxis during therapy. Hematologic response was modified from the response criteria of light chain amyloidosis by combined with serum electrophoresis, immunofixation and serum free light chain. The Overall Neuropathy Limitation Scale (ONLS) was used to assess neurological disability. The neurological response was defined as a scale score reduction of at least 1. Serum VEGF levels were measured with a human Quantikine ELISA Kit. The primary endpoint was hematologic and neurologic response. Secondary endpoints included, clinical and serum VEGF response as well as safety. All patients were followed up monthly for the first three months and every 3 months afterwards.
Results: Forty-one patients were enrolled from March 2014 to November 2014. The median age was 49 years (range, 21-70) with a male predominance at 68%. All patients had mild to severe polyneuropathy with a median ONLS score of 4 (range, 1-10). The monoclonal components were IgAλ (n = 25), IgGλ (n = 13), λ alone (n=1) and biclonal isotype (n=2). All but one had elevated serum VEGF levels with a median level of 5155 pg/mL (range, 534-14328 pg/mL). Other features including peripheral edema (98%), ascites or pleural effusions (46%), organomegaly (93%), gynecomastia (75%), and skin changes (93%) were also common.
All but one patients had completed at least 6 cycles of Rdex therapy. The overall hematologic response was 70% comprised of 47% complete response and 23% partial response. Median time to first hematological response was 2 months (range, 1-9 months). The overall neurologic response was 90.2%. The median ONLS score was decreased from 4 (1-10) to 2 (range, 0-9) and the median time to first neurological response were 1 month (range, 1-9 months). Serum VEGF levels declined significantly from 5155 pg/ml (534-14328 pg/ml) to 1053 pg/ml (447-11864 pg/ml),where 37% and 39% patients achieved VEGF-CR and VEGF-PR, respectively. Rdex was highly effective for patients with extra-vascular volume overload. The initial extra-vascular volume overload responses were observed after a median of 1cycles (range, 1-3) of Rdex therapy. The peripheral edema had disappeared or improved significantly in all patients (100%). Moreover, all three cases (100%) with pulmonary hypertension resolved after lenalidomide therapy.
No treatment-related deaths were observed. No patient discontinued therapy because of drug-related adverse events. Only one (2%) grade 3 rash was observed. Regarding hematological toxicity, three patient (7%) experienced grade 2 neutropenia, and three (7%) had grade 1 anemia. Other non-hematological toxicities included grade 1 or 2 elevated ALT level (51%), fatigue (20%), constipation (22%), diarrhea (15%), and rash (10%).
Median follow-up time was 10 months (range, 2-14 months). Three patients (7%) had disease progression after 3 (n=1) and 9 (n=2) cycles. Among these three patients, two patients died from respiratory failure due to disease progression and one patient had received salvage therapy of autologous stem cell transplantation. Therefore, one-year progression free survival (PFS) and overall survival (OS) were 83% and 89%, respectively.
Conclusion: Combination of low dose lenalidomide and dexamethasone is a effective and safe treatment for patients with newly diagnosed POEMS syndrome.
Disclosures
No relevant conflicts of interest to declare.
Lenalidomide and Dexamethasone for a Patient of POEMS Syndrome Presenting with Massive Ascites