Breakthrough Clinical Results
Health Canada has approved Blenrep (belantamab mafodotin) in combination with bortezomib and dexamethasone, or with pomalidomide and dexamethasone, for adult patients with relapsed or refractory multiple myeloma who have received at least one prior line of therapy. This approval is based on superior efficacy results from the DREAMM-7 and DREAMM-8 phase III trials, showing statistically significant improvements in progression-free survival and overall survival compared to standard of care. Blenrep is the first and only anti-BCMA antibody-drug conjugate approved for multiple myeloma in Canada, offering a differentiated mechanism of action and convenient administration. The most common side effects were eye-related, but manageable.
Key Highlights
- Health Canada approved Blenrep (belantamab mafodotin) in combination with bortezomib/dexamethasone or pomalidomide/dexamethasone for relapsed/refractory multiple myeloma.
- Superior efficacy demonstrated in DREAMM-7 and DREAMM-8 phase III trials, including improved overall survival.
- Blenrep is the first and only anti-BCMA antibody-drug conjugate approved for multiple myeloma in Canada.
- Treatment is convenient, without complex pre-administration or hospitalization.
Incidence and Prevalence
Global Incidence and Prevalence of Multiple Myeloma
According to the most recent data from 2020, multiple myeloma accounted for 176,404 cases globally, representing 14% of 1,278,362 incidence cases of leukemia, lymphoma, and multiple myeloma worldwide.
The global age-standardized rate (ASR) of multiple myeloma incidence was 1.78 (95% UI 1.69-1.87) per 100,000 people in 2020, while the global mortality rate was 1.14 (95% UI 1.07-1.21) per 100,000 people.
Geographical distribution shows significant variation in incidence rates. The highest incidence rates were observed in: - Australia and New Zealand (ASR 4.86 [4.66-5.07]) - Northern America (4.74 [4.69-4.79]) - Northern Europe (3.82 [3.71-3.93])
In contrast, the lowest incidence rates were found in: - Western Africa (0.81 [0.39-1.66]) - Melanesia (0.87 [0.55-1.37]) - Southeastern Asia (0.96 [0.73-1.27])
Gender disparities are evident, with men (1.41 [1.29-1.53]) experiencing higher mortality rates than women (0.93 [0.85-1.02]). Multiple myeloma incidence rates vary from 1.5 to 4.5/100,000/year, depending on the country, with a median age of 69 and a sex ratio of 1.1.
Racial disparities are particularly pronounced in the United States, where Non-Hispanic Black individuals exhibit the highest incidence rates (14.20 [95% CI 12.93, 15.55] per 100,000 population by 2020). Among American Black people, multiple myeloma incidence is more than twice that among Whites, representing one of the highest racial disparities of any cancer.
There is an increasing trend in multiple myeloma incidence globally, particularly affecting: - Men - People aged 50 years or older - Those from high-income countries
Countries with the highest incidence increase in men older than 50 years include Germany (AAPC 6.71 [95% CI 0.75-13.02]), Denmark (3.93 [2.44-5.45]), and South Korea (3.25 [0.69-5.88]).
Several risk factors are associated with increased incidence and mortality, including higher human development index, higher gross domestic product, prevalence of physical inactivity, overweight and obesity, and diabetes.
Despite the rising incidence, there is a decreasing trend for multiple myeloma mortality globally, with this trend being more evident in women.
Socioeconomic status (SES) also plays a significant role in survival outcomes. Patients with high SES had a median overall survival of 62.8 months compared to 53.7 months and 48.6 months for middle and low SES, respectively. After controlling for various factors, patients with low SES had a 54% increase in mortality rate relative to patients with high SES.
Compared to multiple myeloma, Waldenström's macroglobulinemia is 3-4 times less frequent, whereas monoclonal gammopathy of unknown significance (MGUS) is much more common.
Study Design Parameters
Multiple Myeloma Study Design Parameters and Endpoints
Study Designs
Multiple myeloma clinical trials employ various methodological approaches to evaluate treatment efficacy:
- Randomized controlled trials represent the predominant design for evaluating treatment efficacy
- Retrospective analyses have been used to evaluate bortezomib as first-line therapy in newly diagnosed patients
- Meta-analysis approaches have examined survival data according to socioeconomic status
- Mathematical modeling has been applied to analyze tumor response data from randomized controlled trials
- Integrated proteomic and metabonomic analyses have been conducted on plasma samples to evaluate treatment responses
- Systematic reviews have been performed to assess outcomes related to high-risk cytogenetic abnormalities
Primary Endpoints
Key primary endpoints in multiple myeloma trials include:
- Overall response rate serves as a primary endpoint in several studies
- Progression-free survival (PFS) is commonly used as either a primary or secondary endpoint
- Overall survival (OS) is frequently assessed as a key endpoint
- Minimal residual disease (MRD) detection has emerged as an important endpoint, with meta-analyses showing MRD negativity correlates with longer PFS and OS
- The 2016 updated IMWG response criteria incorporate MRD as the deepest level of treatment response
Secondary Endpoints
Multiple myeloma trials often assess:
- Renal response parameters
- Safety and toxicity profiles, particularly bortezomib-induced peripheral neuropathy
- Time to first renal response
- Biomarker identification for treatment resistance
- Cytogenetic abnormalities as prognostic indicators
Patient Populations
Clinical trials typically focus on specific patient subgroups:
- Newly diagnosed multiple myeloma (NDMM) patients
- Relapsed/refractory multiple myeloma (RRMM) patients
- Patients stratified by socioeconomic status
- Patients with renal impairment
- Patients with varying cytogenetic risk profiles
Assessment Methods
Multiple myeloma trials employ various techniques:
- Multiparameter flow cytometry for detecting clonal plasma cells
- Immunohistochemistry for plasma cell detection
- Fluorescence in situ hybridization studies, particularly CD138+ sorted FISH
- Circulating cell-free DNA detection as a non-invasive method
- Imaging techniques combined with molecular tests
Specific Trial Examples
The IKEMA Phase III study (NCT03275285): * Evaluated isatuximab plus carfilzomib and low-dose dexamethasone versus carfilzomib/dexamethasone in RRMM * Used progression-free survival as the primary endpoint * Responses were determined by an independent review committee using 2016 IMWG criteria * Enrolled 302 randomized patients between November 2017 and March 2019
Maintenance therapy trials have shown: * Lenalidomide is superior to thalidomide due to reduced neurotoxicity * Bortezomib-based maintenance shows evidence for OS benefit in high-risk MM and renal dysfunction
Novel immunotherapies are being incorporated into the treatment landscape, with current approved immunotherapeutic agents like CAR-T cells limited to patients with at least 3-4 prior lines of treatment.
Drug used in other indications
Clinical Trials of Blenrep Combination Therapy Beyond Multiple Myeloma
Based on a thorough review of the available information, there is no data indicating that Blenrep (belantamab mafodotin) in combination with bortezomib and dexamethasone is currently being trialed for any indications other than multiple myeloma.
The existing clinical research appears to focus on various treatment combinations for multiple myeloma, including therapies with daratumumab, elotuzumab, ixazomib, and bortezomib in different combinations. However, specific trials investigating Blenrep (belantamab mafodotin) - either alone or in the requested combination with bortezomib and dexamethasone - for non-multiple myeloma indications are not documented in the available information.
Without confirmed clinical trials for other indications, there is consequently no information available regarding the intervention models that might be employed in such trials.
For patients or healthcare professionals interested in the latest developments regarding Blenrep combination therapies, consulting current clinical trial registries or specialized oncology resources would provide the most up-to-date information on any emerging research in this area.