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Development of target-specific treatments in multiple myeloma.

ABSTRACT: In the last decade, the novel agents lenalidomide, bortezomib, and thalidomide have dramatically improved outcomes for patients with multiple myeloma (MM). A number of new therapies with precise targets involved in MM cell growth and replication are now in development and have the potential for further improvements. Second-generation proteasome inhibitors and thalidomide derivatives may offer increased efficacy and safety. Investigational therapies with rationally selected targets in MM include inhibitors of histone deacetylase, heat shock protein 90, mammalian target of rapamycin, BCL2, Akt, mitogen-activated protein kinase, and telomerase. In addition, monoclonal antibodies directed against several targets have been developed and many are showing promise in initial clinical trials in MM. Interest in the ancient remedy of arsenic trioxide has been revived because of its proapoptotic effects on mitochondria, despite its established toxicities. In general, combination regimens are proving the most efficacious, which is to be expected given the multiple overlapping pathways responsible for MM growth and progression.

SUBMITTER: Chanan-Khan AA

PROVIDER: S-EPMC3698607 | biostudies-other | 2010 Oct

REPOSITORIES: biostudies-other

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Development of target-specific treatments in multiple myeloma.

Chanan-Khan Asher A AA Borrello Ivan I Lee Kelvin P KP Reece Donna E DE

British journal of haematology 20100707 1

In the last decade, the novel agents lenalidomide, bortezomib, and thalidomide have dramatically improved outcomes for patients with multiple myeloma (MM). A number of new therapies with precise targets involved in MM cell growth and replication are now in development and have the potential for further improvements. Second-generation proteasome inhibitors and thalidomide derivatives may offer increased efficacy and safety. Investigational therapies with rationally selected targets in MM include ...[more]

PMID: 20618339

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Project description:Background: Investigational and marketed drugs for the treatment of multiple myeloma (MM) are associated with a range of characteristics and uncertainties regarding long term side-effects and efficacy. This raises questions about what matters most to patients living with this disease. This study aimed to understand which characteristics MM patients find most important, and hence should be included as attributes and levels in a subsequent quantitative preference survey among MM patients. Methods: This qualitative study involved: (i) a scoping literature review, (ii) discussions with MM patients (n = 24) in Belgium, Finland, Romania, and Spain using Nominal Group Technique, (iii) a qualitative thematic analysis including multi-stakeholder discussions. Results: MM patients voiced significant expectations and hopes that treatments would extend their lives and reduce their cancer signs and symptoms. Participants however raised concerns about life-threatening side-effects that could cause permanent organ damage. Bone fractures and debilitating neuropathic effects (such as chronic tingling sensations) were highlighted as major issues reducing patients' independence and mobility. Patients discussed the negative impact of the following symptoms and side-effects on their daily activities: thinking problems, increased susceptibility to infections, reduced energy, pain, emotional problems, and vision problems. MM patients were concerned with uncertainties regarding the durability of positive treatment outcomes, and the cause, severity, and duration of their symptoms and side-effects. Patients feared short-term positive treatment responses complicated by permanent, severe side-effects and symptoms. Conclusions: This study gained an in-depth understanding of the treatment and disease-related characteristics and types of attribute levels (severity, duration) that are most important to MM patients. Results from this study argue in favor of MM drug development and individual treatment decision-making that focuses not only on extending patients' lives but also on addressing those symptoms and side-effects that significantly impact MM patients' quality of life. This study underscores a need for transparent communication toward MM patients about MM treatment outcomes and uncertainties regarding their long-term efficacy and safety. Finally, this study may help drug developers and decision-makers understand which treatment outcomes and uncertainties are most important to MM patients and therefore should be incorporated in MM drug development, evaluation, and clinical practice.

Dataset Information

Development of target-specific treatments in multiple myeloma.

Publications

Development of target-specific treatments in multiple myeloma.

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