Influence of Cytogenetics in Patients with Relapsed and Refractory Multiple Myeloma (MM) Treated with Carfilzomib (CFZ).
Bibliographic record
Abstract
Abstract Abstract 1827 Poster Board I-853 Background It is now well established that cytogenetic abnormalities can affect the responses to therapies in multiple myeloma (MM) patients. Bortezomib, used alone or in combination with other agents, has been shown to overcome the adverse impact of several common unfavorable cytogenetic features. More recently, responses with lenalidomide and dexamethasone have been reported in patients with some types of unfavorable cytogenetics. Carfilzomib (CFZ) is a novel proteasome inhibitor that has demonstrated single agent activity in relapsed and/or refractory MM patients. The objective of this analysis was to provide the first preliminary information on the influence of cytogenetics in patients (pts) with relapsed and/or refractory MM treated with CFZ. Methods We evaluated 79 pts treated on two single agent CFZ studies (PX-171-003 and PX-171-004) in relapsed and/or refractory myeloma in which metaphase cytogenetics and/or FISH analysis for del 13q, t(4:14), and t(14;16) chromosomal abnormalities were available. Metaphase cytogenetics was conducted for all pts in the analysis; fluorescence in situ hybridization (FISH) results were available for 28 of the 79 pts. Twenty-one pts with relapsed and refratory MM (PX-171-003) and 58 pts with relapsed or refractory MM (PX-171-004) received CFZ at 20 mg/m2 IV on days 1, 2, 8, 9, 15, and 16 in a 28-day cycle for up to 12 cycles. For this analysis, responders were defined as pts who achieved at least a Minor Response (MR) [MR + Partial Response (PR) + Very Good Partial Response (VGPR) + Complete Response (CR)] by IMWG and EBMT criteria. Results The median age of analysed pts was 63 yrs and 100% of pts were relapsed, with 70% refractory to their last therapy. Analysis of their histories demonstrated prior thalidomide treatment in 75% of pts, prior lenalidomide treatment in 57%, prior bortezomib treatment in 55%, and prior stem cell transplantation in 84%. The response rate (≥MR) for the entire group of patients was 40.5%. Twenty three of 79 pts had at least one of the abnormalities. The presence of del 13q, t(4;14), or t(14;16) did not significantly change the response rates, with 43.5% of pts with one or more abnormalities responding compared to 39.3% with none. The median time to progression (TTP) for all patients in this analysis was 203 days. The TTP for pts with one or more of the abnormalities was 195 days and was not significantly different from the TTP of 208 days for pts with none of the abnormalities (Figure; P > 0.05). Conclusion In this preliminary analysis, CFZ showed comparable activity in relapsed and relapsed/refractory MM with del 13q and/or t(4:14), and/or t(14;16) versus none of these abnormalities, with ≥MR in 43.5% vs. 39.3% of patients, and a TTP of 195 vs. 208 days, respectively. Updated efficacy data and TTP data will be presented at the meeting. Disclosures Jakubowiak: Millennium: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Centocor Ortho Biotech: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Exelixis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers-Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Wang:Proteolix, Inc.: Research Funding. Jagannath:Millennium: Honoraria, Membership on an entity's Board of Directors or advisory committees; Merck: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees. Siegel:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Millennium: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Stewart:Takeda-Millenium, Celgene, Novartis, Amgen: Consultancy; Takeda, Millenium: Research Funding; Genzyme, Celgene, Millenium, Proteolix: Honoraria. Kukreti:Celgene: Honoraria. Lonial:Celgene: Consultancy; Millennium: Consultancy, Research Funding; BMS: Consultancy; Novartis: Consultancy; Gloucester: Research Funding. McDonagh:Proteolix: Research Funding. Vallone:Proteolix, Inc.: Employment. Kauffman:Proteolix, Inc.: Employment. Vij:Proteolix: Research Funding.
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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 | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 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".