Primary Treatment of Light Chain (AL) Amyloidosis with Bortezomib, Lenalidomide and Dexamethasone (VRD)

• Published in: Blood 2018-11, Vol.132 (Supplement 1), p.3248-3248
• Main Authors: Kastritis, Eftathios, Dialoupi, Ioanna, Gavriatopoulou, Maria, Roussou, Maria, Kanellias, Nikolaos, Tselegkidi, Marini, Papadopoulou, Elektra, Ziogas, Dimitrios C., Stamatelopoulos, Kimon, Manios, Efstathios, Ntalianis, Argyrios, Eleutherakis-Papaiakovou, Evangelos, Migkou, Magdalini, Despina, Fotiou, Papanikolaou, Asimina, Gakiopoulou, Charikleia, Psimenou, Erasmia, Tatouli, Ioanna, Ntanasis-Stathopoulos, Ioannis, Bagratuni, Tina, Papathoma, Alexandra, Spyropoulou-Vlachou, Marilyn, Giannouli, Stavroula, Terpos, Evangelos, Dimopoulos, Meletios A
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2018-99-111608

The aim of therapy in AL amyloidosis is to rapidly eliminate the production of toxic, amyloidogenic light chains by targeting the plasma cell clone. Especially for patients with advanced cardiac involvement, a rapid hematologic response may be critical, while, the depth of response is important in order to maximize the probability of organ response. Bortezomib with the addition of dexamethasone with either cyclophosphamide (CyBorD) or melphalan (BMDex) remain the most commonly used primary treatment. In myeloma multiple (MM) patients the combinations of bortezomib with an IMiD [thalidomide (VTD) or lenalidomide (VRD)] are very effective and widely used in newly diagnosed patients. In AL amyloidosis the tumor clone is usually of low burden without adverse prognostic features ; thus, the VRD regimen should be particularly effective. However, IMiDs have unique toxicity in patients with AL and their tolerability is poorer than in MM patients and lower doses of IMiDs are commonly used in AL patients. Here we report our experience with a VRD light regimen as primary therapy in consecutive patients with AL amyloidosis. From March 2017, 30 consecutive patients (28 evaluable at the day of this report) treated at the Department of Clinical Therapeutics, Athens, Greece, received bortezomib 1.3 mg/m2 on days 1, 8 & 15, with lenalidomide (starting at 5 to 15 mg, according to age, cardiac and renal function) on days 1-21 and dexamethasone 20 mg weekly, every 28 days for 8 cycles (VRD regimen). Standard and updated criteria for organ involvement and response evaluation and for hematologic response were used. A rigorous assessment following standard institutional protocol for efficacy and toxicity was followed. Among the 30 patients, 71% were males, median age was 65 years (range 46-84); 75% had cardiac involvement, median NTproBNP was 3649 pg/ml (81- >30000) and per Mayo stage 14%, 54% , 14% and 18% were stage 1, 2, 3A and 3B respectively; 54% had renal involvement with a median eGFR of 59 ml/min/1.73 m2 (range 10-133), renal stage distribution was 13%, 53% and 33% (stages 1, 2 & 3) and no patient required dialysis at the time of initiation of VRD. So far 14 patients have completed the planned 8 cycles, 7 died prior to completion of planned therapy, 1 discontinued per physician's decision and 8 are still on therapy. The starting dose of lenalidomide was 5 mg in 26 (86%), 10 mg in 2 (7%) and 15 mg in 2 (7%) patients. After the first cycle of VRD, 32% patients achieved a V