Botezomib Containing Regimens Provide a Rapid Hematological and Cardiac Response in Patients with AL Amyloidosis
Authors: Jimenez-Zepeda Victor H , Reece Donna , Trudel Suzanne , Chen Christine I. , Tiedemann Rodger E. , Kukreti Vishal 
Published: October 2019

Abstract
Abstract 4064
The spectrum and severity of organ involvement, especially cardiac involvement, usually dictate early outcome, with cardiac biomarkers such as cTnT, NT-ProBNP, and serum uric acid; median survival is only 5.8 months in patients (pts) with high-stage cardiac biomarkers. Since novel therapies have been now been tried in AL amyloidosis, we performed a retrospective review of two different treatment approaches to explore whether the more rapid hematological (HR) that can result from novel therapy produces improved cardiac responses (CardR) and organ responsse (OR) and translates into a greater benefit for pts with poor cardiac reserve.

Methods:
Pts with documented symptomatic AL with cardiac involvement based on functional studies and/or serum biomarkers who received treatment with bortezomib–containing (Bor) regimens or melphalan and dexamethasone (MD) were identified from our institutional amyloidosis database. TnI and BNP values at baseline, 3, 6 and 12 months were recorded. HR, CardR and OR were assessed according to the more recent validation of the criteria response (Leukemia, 2012).

Results:
Thirty-eight pts meeting inclusion criteria were identified, with 25 pts treated with Bor and 13 pts treated with MD from 12/2005 to 10/2011. Clinical characteristics are shown in Table 1. Bor was given as upfront therapy in 9 pts, as second-line in 13 pts and third-line in 3. After a median of 7 cycles of Bor regimens (1–56) and 6 cycles of MD (1–9), a HR was seen in 23 cases (92%) and 13 cases (100%), including: CR in 32% and 31%, VGPR in 56% and 54% and PR in 4% and 15%, respectively, (p=0.491). Pts treated with Bor achieved HR at a median of 6 weeks compared to 10 weeks for MD (p=0.001); 16 patients treated with Bor had already achieved ≥PR at 6 weeks. OR at 6 months was documented in 20 cases treated with Bor (80%) and 3 cases with MD (23%). With respect to cardiac response, a ≥50% decrease of Troponin-I was seen in 9 of 13 and 4 of 11 evaluable patients treated with Bor and MD respectively, while a decrease of BNP of ≥50% was observed in 11 of 13 evaluable cases treated with Bor and 10 of 13 treated with MD at a median of 6 and 5 months in the Bor group and 12 and 12 months in the MD group, respectively (p=0.001). In the Bor group, 23 patients remained progression-free, versus 7 patients in the MD group (p=0.01).
In conclusion, Bor is a safe and well-tolerated therapy for AL patients and shows faster HR and cardiac responses assessed by BNP and TnI than MD. Although this retrospective study has the limitations of selection bias, small numbers, variable entry criteria, and slight differences in treatment regimen, we show that the overall HR and OR rates are similar with both Bor and MD regimens but, importantly, the rapidity of response is better with bortezomib therapy. This is meaningful for patients with poor cardiac reserve in whom a fast response is needed to avoid cardiac complications/early death. Further prospective comparative studies are required with a focus on longer-term outcomes such as overall survival.

Disclosures:
Jimenez-Zepeda: MMRF: Research Funding; Janssen Ortho: Honoraria. Reece:Otsuka: Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Bristol Myers Squibb: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Millinneum Pharmaceuticals: Research Funding; Merck: Consultancy, Honoraria, Research Funding. Chen:Roche: Honoraria; Johnson & Johnson, Lundbeck, Celgene: Consultancy; Johnson & Johnson, Celgene, GlaxoSmithKline: Research Funding. Tiedemann:Janssen: Honoraria; Celgene: Honoraria. Kukreti:Roche: Honoraria.