Once weekly selinexor, carfilzomib, and dexamethasone (XKd) in carfilzomib nonrefractory multiple myeloma (MM) patients.
Bibliographic record
Abstract
8038 Background: Exportin 1 (XPO1) mediates the nuclear export and functional inactivation of tumor suppressor proteins (TSPs), is associated with poor prognosis in MM, and contributes to proteasome inhibitor (PI) and immunomodulatory drug (IMiD) resistance. Selinexor (SEL) is a novel, oral, first-in-class selective inhibitor of nuclear export (SINE) compound that blocks XPO1, forcing the nuclear retention and activation of TSPs. SEL in combination with low dose dexamethasone (dex) ± bortezomib (BOR) is FDA approved for previously treated MM. The synergy of SEL with the PI BOR has been confirmed in the phase 3 BOSTON study in MM patients (pts) with 1-3 prior therapies; once weekly (QW) SEL, QW BOR, and dex (XVd) significantly increased progression-free survival (PFS), time to next therapy, and overall response rate (ORR) as compared to standard twice weekly BOR/dex (Vd), despite XVd using 40% less BOR and 25% less dex than standard Vd. We hypothesized that the addition of QW SEL to the PI carfilzomib (CAR)-dex (XKd) would be an active and tolerable regimen in pts with heavily pretreated MM. Methods: In the XKd arm of the multi-arm Phase 1b/2 STOMP study, SEL at 80 or 100 mg QW was evaluated in combination with CAR at 56 or 70 mg/m2 QW plus dex at 40 mg QW in pts with heavily pretreated MM not refractory to CAR. Study objectives were to determine the maximum tolerated dose and recommended phase 2 dose (RP2D) and assess the safety and activity of the XKd regimen. Results: As of 4Jan2021, 27 pts were enrolled: 18 (67%) were male, median age 71 years (range 50-76), and median of 4 (range 1-8) prior lines of therapy. All 27 pts were previously treated with BOR, 26 (96%) lenalidomide (LEN), 19 (70%) pomalidomide (POM), 18 (67%) daratumumab (dara). The majority (67%) of pts were triple-class pretreated (PI, IMiD, and anti-CD38 mAb), and 44% had triple-class refractory MM. Nine pts (33%) had MM quad-refractory to BOR, LEN, POM, and dara. Common hematologic treatment-related adverse events (TRAEs) (total, grade ≥3) included thrombocytopenia (74%, 56%), anemia (59%, 19%), and neutropenia (30%, 7%). Non-hematologic TRAEs included nausea (67%, 4%), fatigue (52%, 7%), and anorexia (52%, 4%). RP2D was identified as SEL 80 mg QW, CAR 56 mg/m2 QW, and dex 40 mg QW. As of 3Feb2021, ORR was 78% (21/27) with 5 pts reaching CR (19%), 8 VGPR (30%), and 8 PR (30%). Median PFS was 23.7 months. Among 18 pts pretreated with dara, ORR was 67% and median PFS 23.7 months. In 9 pts whose MM was refractory to BOR, LEN, POM, and dara, ORR was 67% with 4 VGPR (44%). Conclusions: In pts with heavily pretreated MM, weekly XKd is highly active with an ORR of 78% and deep responses (≥VGPR 48%) with an overall PFS of 23 months. All AEs including grade 3/4 thrombocytopenia can be managed with appropriate supportive care and dose modifications. These data support further investigation of XKd in pts with previously treated MM including those previously treated with dara.
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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 | 0.000 |
| 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".