Selinexor containing regimens in patients with multiple myeloma (MM) previously treated with anti-CD38 monoclonal antibodies (αCD38 mAbs).
Bibliographic record
Abstract
e20020 Background: Exportin 1 (XPO1) mediates the nuclear export and functional inactivation of tumor suppressor proteins, is required for MM growth, is associated with poor prognosis in MM and mediates resistance to standard MM therapies. Selinexor (SEL) is a first-in-class, oral selective inhibitor of nuclear export (SINE) compound approved in combination with dexamethasone (dex) ± bortezomib for patients (pts) with previously treated MM. Once MM becomes refractory to αCD38 mAb, pts have limited effective treatment options and poor prognosis. Overall response rate (ORR) to the first regimen after refractoriness to an αCD38 mAb is 31%, median progression-free survival (mPFS) is 3.4 months (m), and median overall survival (mOS) is 8.6 m. The doublet SEL-dex (Xd) has shown ORR ̃26% in triple-class (IMID, PI, αCD38 mAb) refractory MM; SEL-based triplets could be more effective in this population. Methods: STOMP (Selinexor and Backbone Treatments of Multiple Myeloma Patients) is a multi-arm, open-label, Phase 1b/2 study evaluating SEL in various triplet combinations. Here, we retrospectively analyzed the efficacy and safety of SEL-containing triplets in pts previously treated with αCD38 mAbs. Pts received SEL-dex (Xd) plus pomalidomide (XPd, n = 19), bortezomib (XVd, n = 4), lenalidomide (XRd, n = 4), daratumumab (XDd, n = 2) or carfilzomib (XKd, n = 18). ORR, mOS, mPFS and adverse events (AEs) were analyzed. Results: Among the 47 pts, median age 64 yrs, female 53%, median time from diagnosis 5.1 yrs, median number of prior regimens 5 (range, 2–11). Prior daratumumab (96%), isatuximab (4%); 96% had MM refractory to aCD38 mAb, 81% had triple-class refractory MM, 74% and 47% were quad- and penta-exposed, 43% and 15% had quad- and penta-refractory MM. αCD38 mAb was included in the immediate prior regimen of 57% of pts and median duration from end of most recent aCD38 mAb therapy to first dose of study treatment was 6.9 weeks (range, 2.6-114.9). ORR was 51% among the 45 evaluable pts, 59% in the XPd arm (n = 17; 2 pts were not efficacy evaluable) and 67% in the XKd arm. ORR was 47% (9/19) among pts with quad-refractory MM and evaluable efficacy. Among all evaluable pts mPFS was 8.8 m (95% CI: 4.9, NE) and mOS was 20.4 m (95% CI: 9.6, NE). Among the 25 pts with αCD38 mAb in their immediate prior regimen, efficacy was similar to that regimen: ORR 52% vs. 45%, mPFS 8.8 vs. 9.3 m. The most common treatment emergent AEs were nausea (72%), anemia (64%), thrombocytopenia (60%), fatigue (57%), which were managed with standard supportive care and dose modifications. Conclusions: SEL-containing triplets in pts with MM previously treated with αCD38 mAbs, most of whom had triple-class refractory MM, exhibit tolerability and comparable effectiveness to their most recent αCD38 mAb-containing regimens. Compared to historical control, mOS was much higher among these patients. Further investigation is warranted. Clinical trial information: NCT02343042.
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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 | 0.000 |
| 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) | 0.001 | 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".