Botezomib Containing Regimens Provide a Rapid Hematological and Cardiac Response in Patients with AL Amyloidosis
Bibliographic record
Abstract
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.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".