Long Term Follow up of the Combination of Bortezomib with Dexamethasone as Initial Treatment for AL Amyloidosis

Abstract Abstract 3048 Until recently, patients with AL amyloidosis had limited treatment options, especially those who were not candidates for high dose therapy, those with severe cardiac involvement or patients who relapsed after initial treatment or never responded to first line alkylators with steroids. Bortezomib (B) with dexamethasone (D) has shown significant activity in patients with AL amyloidosis in patients who relapsed or even those who were refractory to initial treatment. We and others have presented data indicating that BD is active in newly diagnosed patients with AL, inducing responses rapidly but also associated with high rates of complete responses. However, data about long-term follow-up of these patients are limited. Thus, we updated a series of 24, previously untreated patients who received frontline BD. In all patients, treatment started with B at a dose of 1.3 mg/m2 on days 1, 4, 8 & 11 and D was given for 4 consecutive days at a dose of 40 mg per day (days 1–4), every 21 days for up to 6 cycles. The median age of these patients was 70 years (range 42–82) and 46% were males. The median number of involved organs was 2; heart was involved in 83% and kidneys in 63%. Fifty-seven percent were Mayo stage II and 26% were Mayo stage III while 67% had impaired ECOG performance status ≥ 2. The first patient started treatment with BD on September 2005. A median of 5 cycles of BD was given (range 1–6) and 57% of patients received the planned 6 cycles. On intent to treat and according to criteria published by Gertz et al in 2005, 77% of patients achieved a hematologic response including 36% with a hematologic CR. Most of the responses occurred after the first cycle of BD (median time to first response <1 month), while a median of two cycles of BD was needed for CR (median time to CR was 42 days, range 21–84). In 54% of patients an organ response was recorded: 47% of patients with a cardiac involvement achieved a cardiac response and 77% had a reduction of NTproBNP ≥ 30% (which was at least 300 pg/ml), while 60% of patients with a kidney involvement achieved an organ response. Three patients received high dose melphalan with autologous stem cell transplant (HDM-ASCT) after they had completed 6 cycles of BD, 2 while in CR and one in PR. All these 3 patients had achieved organ responses before ASCT. The median follow up for all patients is 31 months. Thirteen patients (54%) have died; most of them due to complications of cardiac amyloidosis and the median survival is estimated to exceed 36 months (patients who underwent ASCT were censored at the time of HDM). Baseline NT-proBNP was the most significant factor independently associated with survival. There were no differences in the baseline characteristics of patients who achieved CR compared to those who achieved a PR as best hematologic response. The median follow up for patients who achieved a CR is 31 months (range 2–55 months). One patient died early due to complications of cardiac amyloidosis, while she had achieved a CR. Among the rest of the patients who achieved a CR but did not receive HDM, all remain alive and without progression for a median of 32 months. Similarly none of the patients who received HDM has relapsed. Among patients who achieved a PR as their best response, 4 (50%) have relapsed and the median progression free survival (PFS) for these patients is 9 months and their median survival is 34 months. In conclusion, BD induces high rates of CRs, in unselected, patients with previously untreated AL amyloidosis, most of whom had features of advanced disease and elevated cardiobiomarkers. i.e. patients that may be excluded form clinical trials. The severity of cardiac involvement remains the most important prognostic factor despite the rapid responses and the high rates of hematologic CRs. It is also of interest to note that CRs may persist even in patients who did not receive any alkylating agents or consolidation with high dose melphalan. A CR is associated with improved survival and should be the primary goal of treatment in patients with AL. Our data indicate that primary treatment with bortezomib based regimens should be evaluated in a phase III trial. Disclosures: Dimopoulos: Ortho-Biotech: Honoraria; Celgene: Honoraria; Millennium: Honoraria.