MO209NUOVI PROTOCOLLI TERAPEUTICI NEI PAZIENTI NON IDONEI AL TRAPIANTO CON AMILOIDOSI AL: FOLLOW UP A LUNGO TERMINE
Authors: Greco Rosita , Botta Cirino , Gentile Massimo , Papalia Teresa 
Published: May 2021

Abstract

Background and Aims
Immunoglobulin light-chain (AL)amyloidosis is a rare life-threatening disease caused by light chains that are toxic to vital organs such as the kidneys. New therapeutic strategies with bortezomib and lenalidomide have improved the prognosis. The aim of our study was to evaluate the long term efficacy of therapeutic protocol utilizing bortezomib in induction and in conditioning with lenalidomide for PRR (partial renal response) AL renal Amyloidosis transplant-ineligible patients.

Method
This is a prospective analysis of 16 transplant-ineligible patients with histological diagnosis of renal amyloidosis admitted to our Nephrology Department from 01/2010 to 01/10/2020. All patients have overt nephrotic syndrome at the diagnosis. Two/thirds of them have renal failure. The diagnosis of amyloid is based on the kidney biopsy finding, by light microscopic examination, of amorphous extracellular Congo red positive deposits, which display characteristic dichroism and apple green birefringence under polarised light. Bortezomib-based (BD) regimen is used (Bortezomib 1.3mg/m2 subcutaneously; Cyclophosphamide 200mg/m2 and Dexamethasone 40mg) for 9 cycles. Hematological and organ response were evaluated according to the novel criteria of the International Society of Amyloidosis. The patients with partial renal response (PRR: decreased of 24 hour urine protein and serum creatinine &gt; 50% over baseline) were treated with cycles of Lenalidomide (dose adjustments for renal function, orally on days 1 trough 21 of each 28-days cycle) in combination with dexamethasone and prophylactic anti-thrombotic treatment.

Results
The mean age was 63±7 years and 7/16 (43.7%) were males. By immunohistochemistry the protein composition of the amyloid deposits was FLC k in 6/16 and FLC lambda in 10/16. Periombelical fat aspirate was positive in 5 patients (31.2%). At onset the mean proteinuria was 13.1 ± 3.6 gr/24h with average MDRD of 37.2 ml/min (III stage CKD), average pro-BNP 420.1 and SIV 12.5 mm. At onset three patients (18.7%) had confirmed multiple myeloma (Clone of plasma cells proliferation &gt; 30% in the bone marrow). 3/16 patients died for cardiac arrhythmia at 3 and 4 months after CyBorD cycles initiation. Therefore CyBorD regimen was completed in 13/16 patients. After 9 CyBorD cycles: 3/13 patients showed a complete renal response (CRR: MDRD &gt; 90 ml/min, proteinuria/24h&lt; 300 mg) and CHR (normal serum FLC ratio); 10/13(76.9%) showed a PRR and PHR (dFLC decrease &gt;50% compared to baseline), one patient died for Sepsis, All patients with CRR or PRR showed a complete cardiological response (normal BNP and SIV). Adverse events during therapy: HZV nevralgy in 3. The 9 patients in PRR were treated with Lenalidomide. After median 6 treatment cycles 7/9 (77.7%) patients showed a CRR and CHR. Haemodialysis was started in 2/9 (22.2%) patients. We decided to discontinue the therapy for adverse events in 3 patients: breast cancer in one, transient troponin I increase and angina in an other patient, pneumonia events in one. The pneumoniae infectious and anginal episodes regressed with drug discontinuation. Median follow-up time from diagnosis of Renal Amyloidosis was 46 months. Median follow-up from the start of Lenalidomide was 36 months. One patients died for breast cancer, but in CRR. All the others patients with CRR (9/13, 69.2%), including the two who suspended Lenalidomide for its toxic effects have been in remission for 30 months on average.

Conclusion
We conclude the following Lenalidomide therapy is very effective at increasing the number of CRR. In addition, the two treatment regimens (induction therapy with CyBorD and conditioning with Lenalidomide) kept patients in remission for more than 30 months on average. Further studies on larger samples are needed to validate the data.