Combination Therapies with Selinexor for Multiple Myeloma

(STOMP Trial)

Recruiting in Palo Alto (17 mi)

+14 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: Karyopharm Therapeutics Inc

Must not be taking: CYP3A4 modulators

Disqualifiers: Amyloidosis, Plasma cell leukemia, HIV, others

No Placebo Group

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This study will independently assess the efficacy and safety of 11 combination therapies in 12 arms, in dose-escalation/-evaluation and expansion phases, for the treatment of patients with relapsed/refractory multiple myeloma (RRMM) and newly diagnosed multiple myeloma (NDMM). The combinations to be evaluated are: * Arm 1: Selinexor + dexamethasone + pomalidomide (SPd); enrollment complete * Arm 2: Selinexor + dexamethasone + bortezomib (SVd); enrollment complete * Arm 3: Selinexor + dexamethasone + lenalidomide (SRd) in RRMM; enrollment complete * Arm 4: Selinexor + dexamethasone + pomalidomide + bortezomib (SPVd); enrollment complete * Arm 5: Selinexor + dexamethasone + daratumumab (SDd); enrollment complete * Arm 6: Selinexor + dexamethasone + carfilzomib (SKd); enrollment complete * Arm 7: Selinexor + dexamethasone + lenalidomide (SRd) in NDMM; enrollment complete * Arm 8: Selinexor + dexamethasone + ixazomib (SNd); enrollment complete * Arm 9: Selinexor + dexamethasone + pomalidomide + elotuzumab (SPEd); enrollment complete * Arm 10: Selinexor + dexamethasone + belantamab mafodotin (SBd); enrollment complete * Arm 11: Selinexor + dexamethasone + pomalidomide + daratumumab (SDPd); enrollment complete * Arm 12: Selinexor + dexamethasone + mezigdomide (SMd); actively recruiting Selinexor pharmacokinetics: * PK Run-in (Days 1-14): Starting in protocol version 8.0, patients enrolled to any arm in the Dose Escalation Phase (i.e., Arm 4 \[SPVd\], Arm 6 \[SKd\], Arm 8 \[SNd\], Arm 9 \[SPEd\], Arm 10 \[SBd\], and Arm 11 \[SDPd\]) will also first be enrolled to a pharmacokinetics (PK) Run-in period until 9 patients have been enrolled to this period to evaluate the PK of selinexor before and after co-administration with a strong CYP3A4 inhibitor. This run-in period does not apply to Arm 12 (SMd).

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are taking strong CYP3A4 inhibitors or inducers, you may need to stop them before participating in the PK Run-in period for certain trial arms.

What data supports the effectiveness of the drug Selinexor for treating multiple myeloma?

Selinexor, when combined with dexamethasone, has shown encouraging effectiveness in treating multiple myeloma, especially in patients who have already tried other treatments. In a study, the combination of Selinexor with bortezomib and dexamethasone resulted in a 63% overall response rate, indicating it can be effective even for those with resistant forms of the disease.

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What safety data exists for Selinexor and Belantamab Mafodotin in treating multiple myeloma?

Belantamab Mafodotin has been associated with eye-related side effects, such as keratopathy (eye damage) and changes in vision, which can lead to treatment discontinuation. Selinexor's common side effects include low blood platelet counts (thrombocytopenia), low sodium levels (hyponatremia), and other blood-related issues. Both drugs require careful monitoring and may need dose adjustments if side effects become severe.

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What makes the drug combination therapy with Selinexor unique for treating multiple myeloma?

The combination therapy with Selinexor is unique because it includes a first-in-class drug that inhibits exportin-1, enhancing the effectiveness of proteasome inhibitors like bortezomib and carfilzomib. This regimen has shown to prolong progression-free survival with a manageable safety profile and lower incidence of peripheral neuropathy compared to standard treatments.

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Eligibility Criteria

Adults over 18 with symptomatic multiple myeloma, either newly diagnosed or relapsed/refractory, can join. They must have measurable disease and be in good enough health to swallow pills and handle treatment side effects. Pregnant women, those with severe liver/kidney issues, recent major surgery patients, or individuals with certain infections or heart problems cannot participate.

Inclusion Criteria

Written informed consent signed in accordance with federal, local, and institutional guidelines

I am 18 years old or older.

My liver is functioning well, as tested within the last 28 days.

Exclusion Criteria

I have been diagnosed with active systemic light chain amyloidosis.

I haven't had blood transfusions or growth factors in the last 14 days.

My multiple myeloma does not produce M-protein or light chains.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

PK Run-in

Selinexor pharmacokinetics run-in period to evaluate PK before and after co-administration with a strong CYP3A4 inhibitor

2 weeks

Multiple blood sample collections on Days 1 and 8

Dose-Escalation

Patients undergo dose-escalation to determine the maximum tolerated dose and recommended phase-2 dose

12 months

Regular visits for dosing and monitoring

Expansion

Phase 2 expansion to assess efficacy and safety of combination therapies

12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Participant Groups

The trial is testing Selinexor combined with other drugs like dexamethasone and chemotherapy agents in different mixtures across 11 groups for treating multiple myeloma. Some groups are closed to new participants. The study includes initial phases to determine safe dosages followed by expansions to assess effectiveness.

Group I: 9: Selinexor, Low-dose DEX, Pomalidomide and Elotuzumab (SPEd) Experimental Treatment 4 Interventions

PK Run-in Period: Selinexor and Clarithromycin: * For the first 9 patients enrolled into this dose escalation arm * 14 day run-in period after which patient will proceed to Dose-Escalation Phase C1D1 Selinexor 40 mg will be dosed on Days 1 and 8. Clarithromycin 500 mg will be dosed twice daily on Days 2-8. PK samples will be collected on Days 1 and 8 at 1, 1.5, 2, 3, 4, 5, 6, 8, and 24 hours post dose. Dose-Escalation Phase: * All patients enrolled into this Arm * Each cycle is of 28 days Cohort 9.1: SEL 20/40/60 mg PO once weekly; DEX 28/20 mg PO twice weekly; POM 4 mg PO QD Days 1-21; Elotuzumab (ELO) 10/20 mg/kg IV will be given once weekly on Days 1,8, 15 and 22 of Cycles 1-2. Starting on Cycle 3 and continuing for future cycles, elotuzumab will be dosed at 20 mg/kg on Day 1 of each cycle only. Cohort 9.3: Selinexor, Dexamethasone, Pomalidomide and Elotuzumab will be dosed at RP2D-9.

Group II: 8: Selinexor, Low-dose dexamethasone, and Ixazomib (SNd) Experimental Treatment 4 Interventions

PK Run-in Period: Selinexor \& Clarithromycin: * For the first 9 patients enrolled into this dose escalation arm * 14 day run-in period after which patient will proceed to Dose-Escalation Phase C1D1 Selinexor 40 mg will be dosed on Days 1 and 8. Clarithromycin 500 mg will be dosed twice daily on Days 2-8. PK samples will be collected on Days 1 and 8 at 1, 1.5, 2, 3, 4, 5, 6, 8, and 24 hours post dose. Dose-Escalation Phase: * All patients enrolled into this Arm * Each cycle is of 28 days Cohort 8.1: SEL 40/60/80/100 mg PO once weekly; DEX 20 mg PO twice weekly; IXA 3/4 mg PO once weekly. Cohort 8.3: Selinexor, Dexamethasone and Ixazomib will be dosed at RP2D-8.

Group III: 7: Selinexor, Low-dose DEX and Lenalidomide (SRd) in NDMM Experimental Treatment 3 Interventions

Each cycle is of 28 days Cohort 7.1: SEL 40/60/80 mg PO once weekly; DEX 40 mg PO once weekly; LEN 25 mg PO Days 1-21. Cohort 7.3: Selinexor, Dexamethasone and Lenalidomide will be dosed at RP2D-7.

Group IV: 6: Selinexor, Low-dose dexamethasone, and Carfilzomib (SKd) Experimental Treatment 4 Interventions

PK Run-in Period: Selinexor and Clarithromycin: * For the first 9 patients enrolled into this dose escalation arm * 14 day run-in period after which patient will proceed to Dose-Escalation Phase C1D1 Selinexor 40 mg will be dosed on Days 1 and 8. Clarithromycin 500 mg will be dosed twice daily on Days 2-8. PK samples will be collected on Days 1 and 8 at 1, 1.5, 2, 3, 4, 5, 6, 8, and 24 hours post dose. Dose-Escalation Phase: * All patients enrolled into this Arm * Each cycle is of 28 days Cohort 6.1: SEL 40/60/80/100 mg PO once weekly on days 1, 8, 15, and 22; DEX 40 mg IV or PO once weekly; Carfilzomib (CAR) 56 or 70 mg/m\^2 IV infusion once weekly on days 1, 8, and 15. Cohort 6.2: SEL 60/80/100 mg PO once weekly on days 1, 8, and 15; DEX 40 mg IV or PO once weekly; CAR 56 or 70 mg/m\^2 IV infusion once weekly on days 1, 8, and 15. Cohort 6.3: Selinexor, Dexamethasone and Carfilzomib will be dosed at RP2D-6.

Group V: 5: Selinexor, Low-dose dexamethasone, and Daratumumab (SDd) Experimental Treatment 3 Interventions

Each cycle is of 28 days Cohort 5.1: SEL 80/100 mg PO once weekly; DEX 40 mg once weekly (IV or PO); DARA: 16 mg/kg IV infusion Cycle 1-2: Once weekly, Cycle 3-6: Every other week, Cycle 6 and greater: Once a month. Cohort 5.2: SEL: 60 mg PO twice weekly; DEX: 40 mg weekly (IV or PO); DARA: 16 milligram per kilogram (mg/kg) IV infusion Cycle 1-2: Once. weekly, Cycle 3-6: Every other week, Cycle 6 and greater: Once a month. Cohort 5.3: Selinexor, Dexamethasone and Daratumumab will be dosed at RP2D-5.

Group VI: 4:Selinexor, Low-dose dexamethasone, Pomalidomide, Velcade (SPVd) Experimental Treatment 5 Interventions

PK Run-in Period: Selinexor and Clarithromycin: * For the first 9 patients enrolled into this dose escalation arm * 14 day run-in period after which patients will proceed to Dose-Escalation Phase C1D1 Selinexor 40 mg will be dosed on Days 1 and 8. Clarithromycin 500 mg will be dosed twice daily on Days 2-8. PK samples will be collected on Days 1 and 8 at 1, 1.5, 2, 3, 4, 5, 6, 8, and 24 hours post dose. Dose-escalation Phase: * All patients enrolled into this Arm * Each cycle is of 28 days. Cohort 4.1: SEL 40/60 mg PO once weekly; DEX 40 mg PO once weekly; POM 4 mg PO Days 1-21; BOR 1.3 mg/m\^2 subcutaneous (SC) once weekly. Cohort 4.3: Selinexor, Dexamethasone, Pomalidomide, Velcade (Bortezomib) will be dosed at RP2D-4.

Group VII: 3: Selinexor, Low-dose DEX, and Lenalidomide (SRd) in RRMM Experimental Treatment 3 Interventions

Each cycle is of 28 days Cohort 3.1: SEL 40/60/80/100 mg PO once weekly; DEX 40 mg PO once weekly; Lenalidomide (LEN) 15/25 mg PO Days 1-21. Cohort 3.2: SEL 40/60/80 mg PO twice weekly; DEX 20 mg PO twice weekly; LEN 15/25 mg PO Days 1-21. Cohort 3.3: Selinexor, Dexamethasone and Lenalidomide will be dosed at RP2D-3.

Group VIII: 2: Selinexor, Low-dose Dexamethasone and Bortezomib (SVd) Experimental Treatment 3 Interventions

Each cycle is of 35 days Cohort 2.1: SEL 60/80/100 mg PO once weekly; DEX 40 mg PO once weekly; Bortezomib (BOR) 1.3 milligram per meter square (mg/m\^2) subcutaneous (SC) once weekly. Cohort 2.2: SEL 40/60/80 mg PO twice weekly; DEX 20 mg PO twice weekly; BOR 1.3 mg/m\^2 subcutaneous (SC) once weekly. Cohort 2.3: Selinexor, Dexamethasone and Bortezomib will be dosed at RP2D-2.

Group IX: 1: Selinexor, Low-dose Dexamethasone and Pomalidomide (SPd) Experimental Treatment 3 Interventions

Each cycle is of 28 days Cohort 1.1: Selinexor (SEL) 60/80/100 mg orally (PO) once weekly (QW); Dexamethasone (DEX) 40 mg PO once weekly; Pomalidomide (POM) 2/3/4 mg PO Days 1-21. Cohort 1.2: SEL 40/60/80 mg PO twice weekly (BIW); DEX 20 mg PO twice weekly; POM 3/4 mg PO Days 1-21. Cohort 1.3: Selinexor, Dexamethasone and Pomalidomide will be dosed at RP2D-1. Cohort 1.4: SEL 40 mg PO QW; DEX 40 mg PO QW; POM 4mg PO once daily (QD) Days 1-21.

Group X: 12. Selinexor + dexamethasone + mezigdomide (SMd) Experimental Treatment 3 Interventions

The dose of selinexor will be formally escalated from 40 mg QW to 60 mg QW in combination with mezigdomide 0.6 mg daily. Mezigdomide dosing may be de-escalated as per 3+3 criteria to 0.3 mg or escalated to 1.0 mg. The dose level that passes DLT evaluation will be considered the MTD for the cohort.

Group XI: 11. Selinexor, Dexamethasone, Pomalidomide, and Daratumumab (SDPd) Experimental Treatment 4 Interventions

Each Cycle is of 28 days Cohort 11.1 SEL 40/60 mg PO once weekly on Days 1, 8, and 15; DEX total 40 mg weekly (IV or PO) single or divided doses on Days 1, 8, 15, and 22; POM 4 mg PO QW Days 1-21; DARA 16 mg/kg IV or SC QW on Days 1, 8, 15 and 22 of Cycles 1-2 and on Days 1 and 15 of Cycles 3-6, Day 1 of every Cycle greater than (\>6). Cohort 11.3 Selinexor, Dexamethasone, Pomalidomide, and Daratumumab will be dosed at RP2D-11.

Group XII: 10. Selinexor, Dexamethasone, and Belantamab Mafodotin (SBd) Experimental Treatment 3 Interventions

Each cycle is of 21 days Cohort 10.1: SEL 40/60/80 mg PO once weekly on Days 1, 8, and 15; DEX 40 mg PO QW on Days 1, 8, and 15; Belantamab Mafodotin (BEL) 2.5 mg/kg IV infusion every 3 weeks (Q3W) Day 1 of each cycle. Cohort 10.3: Selinexor, Dexamethasone, and Belantamab Mafodotin will be dosed at RP2D-10.

Belantamab Mafodotin is already approved in European Union, United States for the following indications:

🇪🇺 Approved in European Union as Blenrep for:

• Relapsed or refractory multiple myeloma

🇺🇸 Approved in United States as Blenrep for:

• Relapsed or refractory multiple myeloma

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Weill Cornell Medicine / NewYork Presbyterian Hospital New York, NY

Vancouver General Hospital Vancouver,, Canada

Banner MD Anderson Cancer Center Gilbert, AZ

Jonnsson Comprehensive Cancer Center / University of Los Angeles Los Angeles, CA

More Trial Locations

Who Is Running the Clinical Trial?

Karyopharm Therapeutics Inc Lead Sponsor

Bristol-Myers Squibb Industry Sponsor

References

1. England pubmed.ncbi.nlm.nih.gov

Selinexor for the treatment of patients with previously treated multiple myeloma. [2022] Multiple myeloma (MM) is an increasingly treatable but still incurable hematologic malignancy. Prognosis has improved significantly over recent years, although further advances remain urgently needed, especially for patients with heavily pre-treated and resistant disease for whom there are limited options. Selinexor is a first-in-class, oral, selective inhibitor of nuclear export (SINE) compound that triggers apoptosis in malignant cells by inducing nuclear retention of oncogene messenger RNAs (mRNAs) and reactivation of tumor suppressor proteins (TSPs). In clinical studies of patients with relapsed and/or refractory MM, selinexor has demonstrated both manageable toxicity and encouraging efficacy.

2. United States pubmed.ncbi.nlm.nih.gov

Selinexor plus low-dose bortezomib and dexamethasone for patients with relapsed or refractory multiple myeloma. [2021] Selinexor is an oral inhibitor of the nuclear export protein exportin 1. Preclinical studies demonstrated synergistic antimyeloma activity between selinexor and proteasome inhibitors (PI) through suppression of NF-κB signaling and nuclear retention of tumor suppressor proteins. We tested selinexor in combination with low-dose bortezomib and dexamethasone (SVd) for the treatment of relapsed or refractory multiple myeloma (MM). The primary objectives of this study were to determine the safety profile, overall response rate (ORR), and a recommended phase 2 dose (RP2D) of SVd. We enrolled 42 patients to receive selinexor (60, 80, or 100 mg orally) plus bortezomib (1.3 mg/m2 subcutaneously) and dexamethasone (20 mg orally) once or twice weekly in 21- or 35-day cycles. Patients had a median of 3 (range 1-11) prior lines of therapy, and 50% were refractory to a PI. Treatment-related grade 3 or 4 adverse events reported in ≥10% of patients were thrombocytopenia (45%), neutropenia (24%), fatigue (14%), and anemia (12%). Incidence (4 patients, 10%) and grade (≤2) of peripheral neuropathy were low. The ORR for the entire population was 63%: 84% ORR for PI nonrefractory and 43% for PI-refractory patients. The median progression-free survival for all patients was 9.0 months; 17.8 months for PI nonrefractory, and 6.1 months for PI refractory. SVd treatment produced high response rates in patients with relapsed or refractory MM, including borezomib-refractory MM, with no unexpected side effects. The RP2D is selinexor (100 mg once weekly), bortezomib (1.3 mg/m2 once weekly for 4 weeks), and dexamethasone (40 mg once weekly) per 35-day cycle. This trial was registered at www.clinicaltrials.gov as #NCT02343042.

3. England pubmed.ncbi.nlm.nih.gov

Selinexor for the treatment of multiple myeloma. [2023] Introduction: Despite unprecedented advances in the treatment of multiple myeloma (MM), almost all patients develop a disease that is resistant to the five most commonly used and active anti-MM agents. The prognosis for this patient population is particularly poor resulting in an unmet need for additional therapeutic options. Exportin-1 (XPO-1) is a major nuclear export protein of macromolecular cargo frequently overexpressed in MM. Selinexor is a first-in-class, oral Selective-Inhibitor-of-Nuclear-Export (SINE) compound that impedes XPO-1. Based on results of the STORM-trial, selinexor in combination with dexamethasone was granted accelerated FDA approval for patients with penta-refractory MM in July 2019.Areas covered: This article summarizes our up-to-date knowledge on the pathophysiologic role of XPO-1 in MM. Furthermore, it reviews the most recent clinical data on selinexor in combination with dexamethasone and other anti-MM agents; and discusses its safety profile, management strategies; and potential future developments.Expert opinion: Selinexor represents a next-generation-novel agent with an innovative mechanism of action that marks a significant advance in the treatment of heavily pretreated MM patients. Ongoing studies investigate its therapeutic potential also in earlier lines of therapy. Additional data is needed to confirm that selinexor and other SINE compounds are a valuable addition to our current therapeutic armamentarium.

4. United States pubmed.ncbi.nlm.nih.gov

Selinexor therapy for multiple myeloma and non-Hodgkin lymphomas. [2023] In this review we highlight the most recent studies furthering the clinical development of selinexor, a novel exportin-1 inhibitor, for the treatment of multiple myeloma and non-Hodgkin lymphomas.

5. United States pubmed.ncbi.nlm.nih.gov

Real World Efficacy and Toxicity of Selinexor: Importance of Patient Characteristics, Dose Intensity and Post Progression Outcomes. [2023] Selinexor is an orally available selective inhibitor of exportin-1 that has offered a new treatment option in relapsed or refractory myeloma (RRMM) either in combination with dexamethasone (Sd) or with bortezomib and dexamethasone (SVd).

6. Switzerland pubmed.ncbi.nlm.nih.gov

Belantamab Mafodotin in Patients with Relapsed/Refractory Multiple Myeloma: Results of the Compassionate Use or the Expanded Access Program in Spain. [2023] Belantamab-mafodotin (belamaf) is a novel antibody-drug conjugate targeting B-cell maturation antigen that showed anti-myeloma activity in patients with relapsed and refractory multiple myeloma (RRMM). We performed an observational, retrospective, and multicenter study aimed to assess the efficacy and safety of single-agent belamaf in 156 Spanish patients with RRMM. The median number of prior therapy lines was 5 (range, 1-10), and 88% of patients were triple-class refractory. Median follow-up was 10.9 months (range, 1-28.6). The overall response rate was 41.8% (≥CR 13.5%, VGPR 9%, PR 17.3%, MR 2%). The median progression-free survival was 3.61 months (95% CI, 2.1-5.1) and 14.47 months (95% CI, 7.91-21.04) in patients achieving at least MR (p < 0.001). Median overall survival in the entire cohort and in patients with MR or better was 11.05 months (95% CI, 8.7-13.3) and 23.35 (NA-NA) months, respectively (p < 0.001). Corneal events (87.9%; grade ≥ 3, 33.7%) were the most commonly adverse events, while thrombocytopenia and infections occurred in 15.4% and 15% of patients, respectively. Two (1.3%) patients discontinued treatment permanently due to ocular toxicity. Belamaf showed a noticeably anti-myeloma activity in this real-life series of patients, particularly among those achieving MR or better. The safety profile was manageable and consistent with prior studies.

7. United States pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Belantamab Mafodotin for Patients with Relapsed or Refractory Multiple Myeloma. [2023] On August 5, 2020, the FDA granted accelerated approval to belantamab mafodotin-blmf (BLENREP; GlaxoSmithKline) for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least four prior therapies including an anti-CD38 monoclonal antibody, a proteasome inhibitor, and an immunomodulatory agent. Substantial evidence of effectiveness was obtained from the phase II, multicenter DREAMM-2 trial. Patients received belantamab mafodotin 2.5 or 3.4 mg/kg intravenously once every 3 weeks until disease progression or unacceptable toxicity. The trial demonstrated an overall response rate of 31% in the 2.5 mg/kg cohort and 34% in the 3.4 mg/kg cohort. Keratopathy was the most frequent adverse event, occurring in 71% and 77% of patients, respectively. Other ocular toxicities included changes in visual acuity, blurred vision, and dry eye. The U.S. prescribing information for belantamab mafodotin includes a boxed warning for ocular toxicity, and belantamab mafodotin is available only through a restricted program under a Risk Evaluation and Mitigation Strategy. This article summarizes the data and the FDA review process supporting accelerated approval of belantamab mafodotin 2.5 mg/kg intravenously once every 3 weeks. This approval may be contingent upon verification and description of clinical benefit in confirmatory trial(s).

8. England pubmed.ncbi.nlm.nih.gov

Corneal Epithelial Findings in Patients with Multiple Myeloma Treated with Antibody-Drug Conjugate Belantamab Mafodotin in the Pivotal, Randomized, DREAMM-2 Study. [2020] Patients with relapsed or refractory multiple myeloma (RRMM) represent an unmet clinical need. Belantamab mafodotin (belamaf; GSK2857916) is a first-in-class antibody-drug conjugate (ADC; or immunoconjugate) that delivers a cytotoxic payload, monomethyl auristatin F (MMAF), to myeloma cells. In the phase II DREAMM-2 study (NCT03525678), single-agent belamaf (2.5 mg/kg) demonstrated clinically meaningful anti-myeloma activity (overall response rate 32%) in patients with heavily pretreated disease. Microcyst-like epithelial changes (MECs) were common, consistent with reports from other MMAF-containing ADCs.

9. Switzerland pubmed.ncbi.nlm.nih.gov

Efficacy and safety of belantamab-mafodotin in triple-refractory multiple myeloma patients: A multicentric real-life experience. [2022] Belantamab-mafodotin is an innovative and selective treatment for multi-refractory/relapsed multiple myeloma (MM) patients; however, available real-life experiences on efficacy and safety are limited. In this real-world multicentric retrospective study, we enrolled 28 MM patients treated in four Hematology units of Campania region, Italy, who received a median of six treatment lines prior to belantamab-mafodotin. The overall response rate (ORR) was 40% (complete remission, CR, 11%; very good partial remission, VGPR, 11%; and partial remission, PR, 18%), with a median progression-free survival (PFS) and overall survival (OS) of 3 and 8 months, respectively. One of the most frequent drug-related adverse events was keratopathy observed in nine (32%) patients, leading to therapy discontinuation in only three (11%) of them. Moreover, 22 out of 28 total patients who were treated with at least two administrations achieved an ORR of 50% (CR, 14%; VGPR, 14%; and PR, 22%) with a median PFS and OS of 5 and 11 months, respectively. In conclusion, our multicentric study confirmed efficacy and safety of belantamab-mafodotin in triple-refractory MM patients even in the real-life setting.

10. New Zealand pubmed.ncbi.nlm.nih.gov

Profile and Management of Toxicity of Selinexor and Belantamab Mafodotin for the Treatment of Triple Class Refractory Multiple Myeloma. [2021] Treatment options are limited for multiple myeloma patients who have developed four/five drug-refractory disease. Selinexor (Sel) and belantamab mafodotin (belamaf) were recently approved by the US FDA for treatment of RRMM. The toxicity profile of these drugs is a concern since these agents are used in patients who have already undergone multiple lines of treatment. In this review, we discuss the toxicity profile and strategies for the management of toxicities of Sel and belamaf for the treatment of RRMM. We conducted a comprehensive literature search on PubMed, Embase, Cochrane, and Clinicaltrials.gov using the terms "selinexor", "belantamab", "belamaf", and "multiple myeloma" without applying any limitations based on the date of the study, language, or country of origin. The most common hematological toxicity associated with these two drugs is thrombocytopenia. Cytopenias, constitutional symptoms, gastrointestinal effects, and hyponatremia are the major toxicities of Sel. Keratopathy and anemia are the major toxicities of belamaf. Treatment modifications and dose interruption are usually needed when side effects are more than grade II. As these are newer drugs with limited data, continuous surveillance and monitoring are warranted during the treatment course with early mitigation strategies.

11. France pubmed.ncbi.nlm.nih.gov

Selinexor-Bortezomib-Dexamethasone: A Review in Previously Treated Multiple Myeloma. [2023] Selinexor [Nexpovio® (EU); Xpovio® (USA)] is a first-in-class, selective exportin-1 inhibitor. Oral selinexor once weekly in combination with subcutaneous bortezomib once weekly and oral dexamethasone twice weekly (selinexor-bortezomib-dexamethasone) is approved in the EU and USA for the treatment of adult patients with multiple myeloma who have received at least one prior therapy. In the open-label, randomized, phase 3 BOSTON trial, this regimen significantly prolonged progression-free survival (PFS) compared with the standard bortezomib-dexamethasone regimen in patients with previously treated multiple myeloma. Selinexor-bortezomib-dexamethasone had a generally manageable tolerability profile and an acceptable safety profile in BOSTON, with a lower incidence of peripheral neuropathy (a bortezomib-induced toxicity) compared with bortezomib-dexamethasone. The triplet regimen uses less bortezomib and dexamethasone during the first 24 weeks of treatment. The efficacy and safety profiles of selinexor-bortezomib-dexamethasone, combined with its once-weekly administration of selinexor and bortezomib, make it a useful additional triplet therapy option for previously treated multiple myeloma.

12. England pubmed.ncbi.nlm.nih.gov

Phase 1 study of selinexor plus carfilzomib and dexamethasone for the treatment of relapsed/refractory multiple myeloma. [2023] Selinexor, an oral Selective Inhibitor of Nuclear Export, targets Exportin 1 (XPO1, also termed CRM1). Non-clinical studies support combining selinexor with proteasome inhibitors (PIs) and corticosteroids to overcome resistance in relapsed/refractory multiple myeloma (RRMM). We conducted a phase I dose-escalation trial of twice-weekly selinexor in combination with carfilzomib and dexamethasone (SKd) to determine maximum tolerated dose in patients with RRMM (N = 21), with an expansion cohort to assess activity in carfilzomib-refractory disease and identify a recommended phase II dose (RP2D). During dose escalation, there was one dose-limiting toxicity (cardiac failure). The RP2D of twice-weekly SKd was selinexor 60 mg, carfilzomib 20/27 mg/m2 and dexamethasone 20 mg. The most common grade 3/4 treatment-emergent adverse events included thrombocytopenia (71%), anaemia (33%), lymphopenia (33%), neutropenia (33%) and infections (24%). Rates of ≥minimal response, ≥partial response and very good partial response were 71%, 48% and 14%, respectively; similar response outcomes were observed for dual-class refractory (PI and immunomodulatory drug)/quad-exposed (carfilzomib, bortezomib, lenalidomide and pomalidomide) patients (n = 17), and patients refractory to carfilzomib in last line of therapy (n = 13). Median progression-free survival was 3·7 months, and overall survival was 22·4 months in the overall population. SKd was tolerable and re-established disease control in RRMM patients, including carfilzomib-refractory patients. Registered at ClinicalTrials.gov (NCT02199665).

13. England pubmed.ncbi.nlm.nih.gov

Once weekly selinexor, carfilzomib and dexamethasone in carfilzomib non-refractory multiple myeloma patients. [2022] Proteasome inhibitors (PIs), including carfilzomib, potentiate the activity of selinexor, a novel, first-in-class, oral selective inhibitor of nuclear export (SINE) compound, in preclinical models of multiple myeloma (MM).