Abstract
3 min readBackground: 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. Aims: To evaluate the safety and activity of VRD combination in newly diagnosed, previously untreated patients with AL amyloidosis. Methods: 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. Results: 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 m 2 (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). Summary/Conclusion: 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.
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