Table 1.
Phase II/III Clinical Trials of XPO1 Inhibitors in Hematologic Malignancies.
| Study/ID | Phase | Disease entity | Regimen | Key outcomes/findings | Reference |
|---|---|---|---|---|---|
| STORM (Part 2) | IIb | RRMM (penta-exposed, triple class RRMM) | Selinexor + dexamethasone | ORR 26%, mDOR 4.4 mo; FDA approval for RRMM | (9) |
| BOSTON | III | RRMM (≥1 prior line) | Selinexor + bortezomib + dexamethasone | mPFS 13.9 (XVd) vs. 9.5 mo (Vd) (HR 0.70; p = 0.0075), ORR 76% (XVd) vs. 62% (Vd) (p = 0.0012); weekly dosing improved tolerability | (40) |
| MARCH | II | RRMM (refractory to PI and IMiDs) | Selinexor + dexamethasone | ORR 29% (25% in triple-class RRMM), mDOR 4.7 mo, mPFS 3.7 mo, mOS 13.2 mo | (42) |
| SADAL | IIb | RR DLBCL (≥2 prior lines) | Selinexor monotherapy | ORR 28%, CR 12%, mDOR 9.3 mo; safety profile manageable in a heavily treated elderly population | (10) |
| SENTRY XPORT-MF-034 | I/III | Myelofibrosis (JAKi-naïve) | Selinexor + ruxolitinib | Ongoing: double-blind, placebo-controlled; evaluate SVR35 and TSS50; Phase 1 data showed 79% and 58%, respectively | (41) |
| NCT02228525 | II | High-risk MDS/AML refractory to HMA | Selinexor monotherapy | ORR 26%, SD 39%, mDOR 6.3 mo, mOS 8.7 mo; selinexor showing response to HMA-refractory MDS/AML | NA |
| NCT05918055 | I/II | High-risk MDS | Eltanexor + decitabine-cedazuridine | Ongoing: determine ORR of eltanexor + HMA combination therapy | NA |
| NA | Ib/II | Newly diagnosed MDS-EB-1/2 | Selinexor + azacitidine | ORR 94%, CR 39% (TP53-mutated, ORR 100%, CR 47%), mPFS 24.2 mo, 2-y OS 84%, 2-y PFS 50% | (43) |
| NCT05736965 | II | Newly diagnosed unfit AML | Selinexor + azacitidine + venetoclax | ORR 90%, CRc 80%, (ELN 2022 classification: adverse risk, ORR 89%, CRc 83%), MRD-negativity, 49% | (44) |
| NA | II | Newly diagnosed AML/MDS | Selinexor + azacitidine + venetoclax | CR/CRi 69%, PR 24% | (45) |
| NCT07437170 | II | Pediatric NUP98-r AML (aged 1–18 y) | Selinexor + intensive chemotherapy | Ongoing | NA |
| SELHEM-2 NCT03071276 | I/II | RR AML (aged ≤24 y) | Selinexor, fludarabine, cytarabine | ORR 54%, CR/CRi 50% | NA |
AML: acute myeloid leukemia; CR: complete response; CRi: complete remission with incomplete hematologic recovery; CRc: composite complete remission; FDA: Food and Drug Administration; ELN: European LeukemiaNet; HMA: hypomethylating agent; HR: hazard ratio; IMiDs: immunomodulatory drugs; JAKi: Janus kinase inhibitor; mDOR: median duration of response; MDS: myelodysplastic syndromes; MDS-EB: myelodysplastic syndromes with excess blasts; mOS: median overall survival; mPFS: median progression-free survival; MRD: minimal residual disease; NA: not available/applicable; NUP98-r: NUP98-rearrangement; ORR: objective response rate; PI: proteasome inhibitor; PR: partial response; RR DLBCL: relapsed/refractory diffuse large B-cell lymphoma; RRMM: relapsed/refractory multiple myeloma; SD: stable disease; SVR35: spleen volume reduction ≥35%; TSS50: total symptom score ≥50%; Vd: bortezomib + dexamethasone; XPO1: exportin-1; XVd: selinexor + bortezomib + dexamethasone.