Minimal Residual Disease (MRD) Assessed By Flow Cytometry in Patients with AL Amyloidosis Treated with Cyclophosphamide, Bortezomib and Dexamethasone (CyBorD)
Bibliographic record
Abstract
Introduction In the field of multiple myeloma (MM), the clinical utility of minimal residual disease (MRD) has been an area of extensive research. The use of MRD assessment in AL amyloid patients is an emerging area of interest. In the present study, we aimed to describe the rate of MRD negativity for patients treated with CyBorD at our Institution. Methods All consecutive AL amyloid patients treated with CyBorD at Tom Baker Cancer Center from 01/13 to 04/17 were evaluated. MRD was assessed by multiparameter flow cytometry as per Euroflow consensus guidelines in patients with confirmed complete response. A p value of Results 41 consecutive patients with newly diagnosed (n=35) and relapsed AL (n=6) who had received CyBorD at our Institution over the defined period were evaluated. 5 patients were excluded due to lack of follow-up or enrolment in clinical trials. Clinical characteristics are shown in Table 1 for the remaining cases (n=36). CyBorD was administered with bortezomib at 1.3-1.5 mg/m 2 SC or IV for 3-4 weeks on a weekly basis in 34 cases and biweekly in 2 patients, cyclophosphamide was given at 300 mg/m 2 on days 1, 8, 15 and 22 and dexamethasone at 20-40 mg/PO on days 1, 8, 15 and 22. After a median of 5 cycles, ORR was seen in 91.6% of cases with a PR of 36.1%, VGPR of 27.8% and CR of 27.8%. MRD negativity was observed in 5/10 cases with complete response. MRD negativity rate of 13.8% was reported for the whole group of patients. Organ and cardiac responses were observed in 36.1% and 27.3%, respectively. Median OS was similar between MRD positive and negative cases (NR vs NR, p=0.1) ( Fig 1a ). However, none of the MRD negative cases has died or progressed. A trend towards better PFS was observed in the MRD negative cases (p=0.06) ( Fig1b ). In conclusion , MRD negativity was observed in ~15% cases of AL patients treated with CyBorD after a median of 5 cycles. Further studies to assess the impact of MRD negativity on clinical outcomes and its role for guided therapy are required. Disclosures Jimenez-Zepeda: Takeda: Honoraria; Janssen: Honoraria; Celgene: Honoraria; Amgen: Honoraria. Neri: Celgene: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding. Bahlis: Amgen: Consultancy, Honoraria, Membership on an entity9s Board of Directors or advisory committees, Research Funding, Speakers Bureau; Takeda: Consultancy, Honoraria, Membership on an entity9s Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Membership on an entity9s Board of Directors or advisory committees, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Membership on an entity9s Board of Directors or advisory committees, Research Funding, Speakers Bureau.
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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 | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 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".