Poster Session II: Myeloma and other monoclonal gammopathies - Clinica
Bortezomib/dexamethasone with cyclophosphamide or melphalan are commonly used as primary treatment for AL amyloidosis, but limited data exist on the safety and activity of bortezomib with IMiDs combinations.
To evaluate the safety and activity of VRD combination in newly diagnosed, previously untreated patients with AL amyloidosis.
Between March 2017 and March 2018, 34 consecutive newly diagnosed patients with AL amyloidosis were treated with VRD; standard organ involvement and updated organ and hematologic response criteria were used.
The median age of all patients was 66.5 years (range 46-84); 71% were males, 75% had cardiac involvement, median NTproBNP was 3649 pg/ml (81- >30000), per Mayo stage 14%, 54%, 14% and 18% were stage 1, 2, 3A and 3B respectively; 54% had renal involvement, median eGFR was 59 ml/min/1.73 m2 (range 10-133) and renal stage distribution was 13%, 53% and 33% for stages 1, 2 & 3. Measurable FLCs (i.e. a dFLC≥40 mg/L) were present in 29 (85%) patients; in 4 patients baseline dFLC was >20 mg/dl and were also evaluable for response. Twenty-two patients completed the planned 8 cycles, 9 died prior to completion of planned therapy, 1 patient discontinued therapy for personal reasons (while in VGPR), 1 discontinued therapy after physician's decision (while in VGPR) and one discontinued due to bortezomib-related toxicity (while in CR). After the first cycle of VRD, 24/34 (70.5%) patients had achieved a hematologic response (42% a VGPR or CR and 27% a PR). After 3 months of VRD, 82% of the evaluable patients (N = 27) had achieved at least VGPR, including CR in 6 (22%), and PR in 5 (18%). After 6 VRD cycles, CR, VGPR and PR rates among evaluable (N = 24) patients were 9 (37.5%), 13 (54%), and 2 (8%) respectively. On intent to treat, best hematologic response was CR in 11/34 (32%) and among CR patients 5/11 were MRD negative by NGF; 17/34 (50%) achieved VGPR and in 9 of them dFLC was <10 mg/dl; 2/34 (7%) achieved a PR. Median time to first response (at least a PR) was 28 days (1 treatment cycle), median time to at least VGPR was 84 days (3 cycles of therapy). Cytogenetics were available in 28 patients; among patients with t(11;14) (N = 7), all achieved at least a VGPR (3 a CR and 4 a VGPR). Organ responses were documented in 12 (35%) patients. Median follow up for all patients is 12.5 months and 6 and 12 month survival is 73.5% (100%, 85% and 71% for stage 1, 2 & 3A patients respectively, but only 20% for stage 3B). Starting lenalidomide dose was 5 mg in 86% of patients. Hematologic toxicity was mild; common non-hematologic toxicities included rash (Gr3/4:16%), infections (≥Gr3:12%), constipation (≥Gr3:9%), peripheral neuropathy (Gr2:20%), while, 37.5% of patients required lenalidomide dose reduction, 27% discontinued lenalidomide before planned therapy completion, 38% required bortezomib dose reduction and 12% discontinued bortezomib. We then compared the efficacy of VRD to that of CyBorD given in 68 patients matched for Mayo stage and baseline dFLC and found a trend for deeper responses at 3 months in patients treated with VRD (≥VGPR in 82% vs 45%) and at 6 months (≥VGPR in 92% vs 61%, p = 0.049).
VRD with weekly bortezomib and low dose lenalidomide is a very effective and rapidly acting regimen that can induce deep hematologic responses within 3 months of therapy. However, toxicity of VRD in patients with AL amyloidosis is significant, despite the use of low doses of lenalidomide.