scholarly journals The role of belantamab mafodotin for patients with relapsed and/or refractory multiple myeloma

2020 ◽  
Vol 11 ◽  
pp. 204062072097981
Author(s):  
Melody R. Becnel ◽  
Hans C. Lee
Keyword(s):  
Multiple Myeloma ◽  
Adverse Events ◽  
Unmet Need ◽  
Regulatory Approval ◽  
Mitigation Strategies ◽  
Antibody Drug Conjugate ◽  
Refractory Multiple Myeloma ◽  
B Cell Maturation ◽  
Immunomodulatory Drug

Belantamab mafodotin (belamaf) is a first-in-class anti-B-cell maturation antigen (BCMA) antibody–drug conjugate (ADC) that recently gained regulatory approval for the treatment of relapsed and/or refractory multiple myeloma (RRMM) patients who have received at least four prior therapies including an anti-CD38 monoclonal antibody (mAb), a proteasome inhibitor (PI), and an immunomodulatory drug (IMiD). As the first BCMA-targeted therapy to be approved in multiple myeloma along with its “off-the-shelf” outpatient administration, belamaf addresses a significant unmet need in RRMM that is refractory to IMiD, PI, and anti-CD38 mAb therapy, otherwise known as triple-class refractory myeloma. Belamaf is also associated with frequent corneal ocular adverse events, which represents a unique toxicity in multiple myeloma therapeutics, and its administration requires a multidisciplinary approach with oncologists and eye care specialists to safely and effectively manage patients on belamaf therapy. In this review, we discuss the preclinical and clinical data leading to the regulatory approval of belamaf, the monitoring and mitigation strategies of corneal ocular adverse events, and its current and future role in the RRMM treatment landscape.

Belantamab mafodotin in the treatment of relapsed or refractory multiple myeloma

2020 ◽  
Vol 16 (34) ◽  
pp. 2783-2798 ◽  
Author(s):  
Semira Sheikh ◽  
Eyal Lebel ◽  
Suzanne Trudel
Keyword(s):  
Multiple Myeloma ◽  
B Cell ◽  
Plasma Cells ◽  
Safety Data ◽  
Unmet Need ◽  
Cell Maturation ◽  
Antibody Drug Conjugate ◽  
Refractory Multiple Myeloma ◽  
B Cell Maturation ◽  
B Cell Maturation Antigen

Multiple myeloma remains an incurable disease, with a large proportion of patients in the relapsed/refractory setting often unable to achieve durable responses. Novel, well-tolerated and highly effective therapies in this patient population represent an unmet need. Preclinical studies have shown that B-cell maturation antigen is nearly exclusively expressed on normal and malignant plasma cells, thereby identifying it as a highly selective target for immunotherapeutic approaches. Belantamab mafodotin (GSK2857916, belamaf) is a first-in-class antibody–drug conjugate directed at B-cell maturation antigen and has shown promising activity in clinical trials. In this review, we provide an overview of belantamab mafodotin as a compound and present the available clinical efficacy and safety data in the treatment of relapsed/refractory multiple myeloma.

scholarly journals How I treat relapsed and/or refractory multiple myeloma

2020 ◽  
Vol 12 (s1) ◽  
Author(s):  
Hans C. Lee ◽  
Claudio Cerchione
Keyword(s):  
Multiple Myeloma ◽  
Nuclear Export ◽  
Histone Deacetylase Inhibitors ◽  
Alkylating Agents ◽  
Treatment Options ◽  
Unmet Need ◽  
Proteasome Inhibitors ◽  
Antibody Drug Conjugate ◽  
Refractory Multiple Myeloma ◽  
Therapeutic Landscape

The expanding therapeutic landscape of relapsed and/or refractory multiple myeloma (RRMM) has contributed to significant improvements in patient outcomes. These have included combinations of proteasome inhibitors (PIs), immunomodulatory drugs (IMiDs), monoclonal antibodies (mAbs), histone deacetylase inhibitors, and/or alkylating agents. More recently, the approval of the first-in-class nuclear export inhibitor selinexor and the first-in-class B-cell maturation antigen (BCMA) antibody-drug conjugate (ADC) belantamab mafodotin has helped address the current unmet need in patients refractory to PI, IMiD, and anti-CD38 mAb directed therapy, otherwise known as triple class refractory myeloma. With the growing number of treatment options in the RRMM therapeutic landscape, the choice and sequencing of drugs and combinations has become increasingly complex. In this review we discuss our approach and considerations in the treatment of both early and late RRRM based on best available data and our clinical experience.

PP455 Cost-effectiveness Of Ixazomib-Based Regimen Compared With Bortezomib-Based Regimen In Chinese Patients With Relapsed/Refractory Multiple Myeloma: A Retrospective Study

2020 ◽  
Vol 36 (S1) ◽  
pp. 36-37
Author(s):  
Pei Wang ◽  
Jing Li ◽  
Yang Yang ◽  
Peng Liu
Keyword(s):  
Multiple Myeloma ◽  
Adverse Events ◽  
Staging System ◽  
Chinese Patients ◽  
Disease Stage ◽  
Control Group ◽  
Therapeutic Effects ◽  
Lower Grade ◽  
Refractory Multiple Myeloma ◽  
Grade 3

IntroductionThe treatment of relapsed/refractory multiple myeloma (RRMM), a common hematological malignancy, remains a great challenge in China, partially due to the limited accessibility to novel agents and inadequate public health insurance coverage. Ixazomib, a novel oral proteasome inhibitor (PI), was approved by the China Food and Drug Administration (CFDA) for RRMM in 2018. While bortezomib, a traditional PI, is the recommended agent in the clinical guideline for MM. Here, we compared their costs and effectiveness.MethodsRRMM patients who has received an ixazomib-based regimen (at least 2 cycles) were analyzed. Using a propensity score matching method, we generated a control group of RRMM patients who received the bortezomib-based regimen. The criteria included the number of treatment lines, age, and the revised international staging system stage (R-ISS) which representing the disease stage for myeloma, and paired at a ratio of 1:2 (allowing one control to match multiples). The difference in hospitalization stay, grade 3/4 adverse events rates, overall response rate (ORR), mortality during treatment, and treatment costs was then compared.ResultsNineteen patients received ixazomib and twenty-seven that received bortezomib were included. The ixazomib-group demonstrated a shorter hospital stay (9 days versus 27 days, p < 0.001), lower grade 3–4 adverse events rates (42.1% versus 55.6%, p < 0.001), higher ORR (63.2% versus 48.1%, p = 0.228), and lower mortality rate during treatment (0% versus 7.4%, p = 0.169) than that of bortezomib-group. The ixazomib group had lower total costs (127,620CNY versus 156,424CNY [18,033USD versus 22,103USD], p > 0.05), lower drug costs (98,376CNY versus 103,307CNY [13,901USD versus 14,598USD], p > 0.05), and the lower costs of supportive treatment (5,507CNY versus 14,701 CNY [778USD versus 2,077USD], p < 0.001). Only in terms of self-funded costs, the bortezomib-based regimen was significantly lower (37,127CNY versus 11,521CNY [5,246USD versus 1,628USD], p < 0.001).ConclusionsCompared with the bortezomib-based regimen, the ixazomib-based regimen has better therapeutic effects on MM patients while saving costs. Hence, it may be preferable for use in the treatment of RRMM in China.

scholarly journals Role of Histone Deacetylase Inhibitors in Relapsed Refractory Multiple Myeloma: A Focus on Vorinostat and Panobinostat

2015 ◽  
Vol 35 (12) ◽  
pp. 1173-1188 ◽  
Author(s):  
Salma Afifi ◽  
Angela Michael ◽  
Mahshid Azimi ◽  
Mabel Rodriguez ◽  
Nikoletta Lendvai ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Histone Deacetylase ◽  
Histone Deacetylase Inhibitors ◽  
Refractory Multiple Myeloma

scholarly journals Evaluation of B cell maturation antigen as a target for antibody drug conjugate mediated cytotoxicity in multiple myeloma

2016 ◽  
Vol 174 (6) ◽  
pp. 911-922 ◽  
Author(s):  
Lydia Lee ◽  
Danton Bounds ◽  
Jennifer Paterson ◽  
Gaelle Herledan ◽  
Katherine Sully ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
B Cell ◽  
Cell Maturation ◽  
Antibody Drug Conjugate ◽  
Drug Conjugate ◽  
B Cell Maturation ◽  
B Cell Maturation Antigen ◽  
Antibody Drug

scholarly journals Single-agent belantamab mafodotin for relapsed/refractory multiple myeloma: analysis of the lyophilised presentation cohort from the pivotal DREAMM-2 study

2020 ◽  
Vol 10 (10) ◽  
Author(s):  
Paul G. Richardson ◽  
Hans C. Lee ◽  
Al-Ola Abdallah ◽  
Adam D. Cohen ◽  
Prashant Kapoor ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Single Agent ◽  
Pathological Finding ◽  
Progression Free Survival ◽  
Antibody Drug Conjugate ◽  
Open Label ◽  
Blurred Vision ◽  
Refractory Multiple Myeloma ◽  
Open Label Phase ◽  
Duration Of Response

Abstract DREAMM-2 (NCT03525678) is an ongoing global, open-label, phase 2 study of single-agent belantamab mafodotin (belamaf; GSK2857916), a B-cell maturation antigen-targeting antibody-drug conjugate, in a frozen-liquid presentation in patients with relapsed/refractory multiple myeloma (RRMM). Alongside the main study, following identical inclusion/exclusion criteria, a separate patient cohort was enrolled to receive belamaf in a lyophilised presentation (3.4 mg/kg, every 3 weeks) until disease progression/unacceptable toxicity. Primary outcome was independent review committee-assessed overall response rate (ORR). Twenty-five patients were enrolled; 24 received ≥1 dose of belamaf. As of 31 January 2020, ORR was 52% (95% CI: 31.3–72.2); 24% of patients achieved very good partial response. Median duration of response was 9.0 months (2.8–not reached [NR]); median progression-free survival was 5.7 months (2.2–9.7); median overall survival was not reached (8.7 months–NR). Most common grade 3/4 adverse events were keratopathy (microcyst-like corneal epithelial changes, a pathological finding seen on eye examination [75%]), thrombocytopenia (21%), anaemia (17%), hypercalcaemia and hypophosphatemia (both 13%), neutropenia and blurred vision (both 8%). Pharmacokinetics supported comparability of frozen-liquid and lyophilised presentations. Single-agent belamaf in a lyophilised presentation (intended for future use) showed a deep and durable clinical response and acceptable safety profile in patients with heavily pre-treated RRMM.

Update on Risk Stratification Model of Smoldering Multiple Myeloma: A Systematic Review

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5512-5512
Author(s):  
Saad Ullah Malik ◽  
Ahmad Abu-Hashyeh ◽  
Muhammad Sardar ◽  
Mohammad M Alhousani ◽  
Emilia Cindy Leigh ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Plasma Cells ◽  
Cell Maturation ◽  
B Cell Maturation ◽  
Smoldering Multiple Myeloma ◽  
Pet Ct ◽  
M Proteins ◽  
Pet Ct Scan ◽  
Bence Jones Proteins

Background: Smoldering multiple myeloma (SMM) was stratified into risk classes based on several models including Mayo clinic and Spanish myeloma working group models. After the revision of diagnostic criteria for multiple myeloma (MM) in 2014, the ultra-high risk SMM patients (>80% clonal plasma cells at two years) were re-classified as active MM patients. Thus, predictors of progression in patients currently diagnosed as SMM are unknown and reassessment of existing models is required. We aim to identify the risk factors associated with progression in SMM patients classified according to updated guidelines. Methods We performed a literature search following PRISMA guidelines and used following bibliographic databases: MEDLINE (Ovid and PubMed), EMBASE, The Cochrane Library and Cochrane Central Register of Controlled Trials (CENTRAL), as well as annual meetings abstracts from inception till 1st,August 2019. We used MeSH and Emtree terms as well as performed open search for "smoldering multiple myeloma", "smoldering myeloma", and "asymptomatic multiple myeloma". Two independent reviewers screened the literature. We used snowballing technique to screen abstracts and reference within articles to include titles. Cochrane collaboration tool was used to asses risk of bias among included studies Results Our search retrieved 419 titles. After going through the titles and abstracts 38 articles were selected for full text review. Final review led to inclusion of 11 articles. Levels of serum M proteins, percentage of bone marrow plasma cells (BMPCs), serum free light chain ratio (FLCr) and PET/CT scan findings of whole body were most consistently and reliably indicated the progression of SMM to MM (Table 1). New studies are suggesting that B-cell maturation levels (BCMA), evolving M-proteins (eMP) and evolving hemoglobin levels (eHb) are also an accurate measure of SMM progression and should be incorporated in the risk stratification models. A study by Gonsalves WI et al. also suggested that levels of circulating clonal plasma cells with a cutoff of 150 was an important prognostic marker in their study. Immunoparesis status and role of Bence Jones proteins in reliably predicting the progression of SMM was debatable because they were significant in univariate analysis but were not significant in multivariate analysis (Table 1). Conclusion Serum M protein levels (2 g/dL), percentage of BMPCs (20%), serum FLCr (20) and PET/CT scan were reliable in predicting the prognosis of smoldering MM. New techniques like B-cell maturation levels(74.4 ng/mL), evolving M-proteins and evolving hemoglobin levels can play a significant role in proposing future risk predictive models of SMM. Role of immunoparesis and Bence Jones proteins is debatable. Table 1 Disclosures Anwer: Seattle Genetics: Membership on an entity's Board of Directors or advisory committees; In-Cyte: Speakers Bureau.

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