GSK's Blenrep-Based Quadruplet Regimen Shows Promising Efficacy and Favorable Safety in Newly Diagnosed Multiple Myeloma: DREAMM-9 Phase I Data

December 21, 2021 /BioValleyBIOON/ --GlaxoSmithKline PLC.(GSK) recently announced new data from the DREAMM-9 Phase I trial. This study is evaluating the efficacy and safety of Blenrep (belantamab mafodotin) in combination with standard-of-care therapies for the early treatment of multiple myeloma (MM). Overall, the trial data indicates thatBy optimizing dosage, schedule, and combination therapy, corneal events associated with Blenrep may be reduced in patients receiving early treatment.. These data will help further research and evaluate the potential of Blenrep in a broader patient population.

Blenrep is an antibody-drug conjugate (ADC) targeting B-cell maturation antigen (BCMA), which has been approved in the United States and the European Union for the indication: as a monotherapy for the treatment of adult patients with relapsed or refractory multiple myeloma (MM) who have previously received at least four types of therapies (including an anti-CD38 antibody, a proteasome inhibitor, and an immunomodulatory agent).

It is worth mentioning that,Blenrep is the world's first approved BCMA-targeted therapy., a first-in-class humanized anti-BCMA therapy, is applicable to patients whose condition progresses despite receiving current standard care. Blenrep employs a multi-faceted mechanism of action targeting BCMA, a cell surface protein that plays a crucial role in plasma cell survival and is expressed on multiple myeloma cells.

GSKTumorGlobal Head of Development Hesham Abdullah stated, "We remain committed to addressing unmet needs by evaluating Blenrep in combination with standard-of-care therapies in earlier treatment lines, as well as assessing different dosing regimens to optimize efficacy and safety in these settings. These promising data highlight the potential of exploring Blenrep as part of a combination regimen to improve outcomes for patients with multiple myeloma."

Mechanism of Action of Belantamab Mafodotin

DREAMM-9 Trial: This Phase I trial is being conducted in newly diagnosed multiple myeloma patients (n=36) who are ineligible for transplant, evaluating a four-drug regimen consisting of Blenrep and standard of care (bortezomib + lenalidomide + dexamethasone [VRd]). Preliminary results show that in the cohort using an extended dosing schedule and low dose, the incidence of corneal events was low while maintaining a very high overall response rate (ORR).

The doses varied across the five cohorts in the DREAMM-9 trial. Cohort 1 received 1.9 mg/kg Q3/4W; Cohort 2 received 1.4 mg/kg Q6/8W; Cohort 3 received 1.9 mg/kg Q6/8W; Cohort 4 received 1.0 mg/kg Q3/4W, and Cohort 5 received 1.4 mg/kg Q3/4W.The ORR observed in Cohort 1 (n=12), Cohort 3, and Cohort 5 (n=6) was 100%., inThe ORR observed in Cohort 2 and Cohort 4 was 83%.(n=5/6). At least 50% of patients in each cohort achieved a very good partial response (VGPR) or better, with the highest rates observed in Cohort 1 and Cohort 5 (100% for each cohort). In Cohort 1, 7 out of 9 patients achieved minimal residual disease (MRD) negative status at the first assessment after reaching VGPR.

In the DREAMM-9 trial, no new adverse events (AEs) related to Blenrep were reported. The majority of patients experienced treatment-related adverse events, which were generally resolved through dose adjustments. The most common adverse events leading to dose modifications were thrombocytopenia, neutropenia, and corneal events. All patients experiencing corneal events continued to receive Blenrep treatment.

DREAMM-9 Chief Investigator, Dr. Saad Z. Usmani, Director of the Myeloma Division at Memorial Sloan Kettering Cancer Center, stated: "For newlyDiagnosisNon-complianceStem CellsFor transplant-eligible multiple myeloma patients, exploring new first-line combination therapies is crucial to improving survival. We believe these preliminary results from the DREAMM-9 trial demonstrate the potential of the Blenrep combination regimen, with many patients achieving very good partial responses or better, while showing consistent safety outcomes. This underscores the potential of this regimen to become an important treatment option for these patients."

BCMA-targeted MM immunotherapies under investigation (Source: PMID: 31277554)

Multiple Myeloma (MM) is the second most common hematological malignancy after non-Hodgkin lymphoma.TumorIn recent years, despite significant advances in chemotherapy, proteasome inhibitors, immunomodulatory thalidomide derivatives, and CD38-targeted antibodies, almost all patients eventually relapse. Therefore, there is an urgent need for new treatment options. The MM market was close to 14 billion USD in 2017 and is expected to reach nearly 29 billion USD by 2027.

BCMA is an extremely important B cellBiomarker, widely present on the surface of MM cells, has become a target in MM and other hematologic malignancies in recent years.TumorA very popular immunotherapy target. Currently,Immunotherapy targeting BCMAMore than 20 types, mainly divided into 3 categories:Chimeric Antigen Receptor T-Cell Therapy (CAR-T, Bristol-Myers Squibb/Bluebird Bio,NovartisRepresentatives), bispecific antibodies (BsAb, represented by Amgen), antibody-drug conjugates (ADC,GlaxoSmithKline PLC.As a representative).

Blenrep is a novel humanized Fc-engineered anti-BCMA monoclonal antibody conjugated to the cytotoxic agent MMAF (monomethyl auristatin-F) via a non-cleavable linker (drug-linker technology from Seattle).GeneticsADC drugs conjugated with authorization. Blenrep binds to BCMA on the surface of MM cells through anti-BCMA monoclonal antibodies, and is rapidly internalized by MM cells, where it is degraded in lysosomes and releases the non-permeable MMAF within the MM cells to take effect. MMAF is a mitotic inhibitor, an anti-tubulin compound that inhibits cell division by blocking microtubule polymerization, which can cause...TumorCells arrest at G/M phase and induce caspase-3-dependentApoptosisIn addition, Blenrep can also induce NK cell-mediated ADCC (antibody-dependent cell-mediated cytotoxicity), while inducing macrophage-mediated ADCP (antibody-dependent cell-mediated phagocytosis).

Blenrep selectively targets MM cells through multiple cytotoxic mechanisms of action, offering a highly promising next-generation immunotherapy option for this type of cancer.. Currently, Blenrep is also being developed for other advanced hematologic malignancies expressing BCMA.TumorPatient. (Bioon.com)

Source of the original text:New data presented at ASH 2021 highlight potential of Blenrep (belantamab mafodotin-blmf) in combination with standard of care therapies in earlier lines of multiple myeloma treatment