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Proteasome Inhibitors in the Treatment of Multiple Myeloma and AL Amyloidosis

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Resistance to Proteasome Inhibitors in Cancer

Part of the book series: Resistance to Targeted Anti-Cancer Therapeutics ((RTACT))

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Abstract

Therapeutic advances in the last decade have led to improved outcomes for people diagnosed with multiple myeloma (MM) and primary systemic (AL) amyloidosis. Foremost among these advances is the incorporation of proteasome inhibitors (PIs) and immunomodulatory drugs (IMiDs) into treatment regimens. Induction regimens for MM which incorporate one or both of these drug classes are associated with response rates ranging from 80 to 100 % in various studies. Myeloma remains a generally incurable disease with most patients relapsing within 5 years of initial therapy. Specific “high-risk” cytogenetic abnormalities in the malignant clone predict particularly short disease control. Results of therapy for relapsed disease are typically inferior to initial treatment, both in terms of likelihood and duration of response. Thus, resistance to proteasome inhibitor-based therapies, both inherent and acquired, remains a problem in the therapy of clonal plasma cell disorders. This chapter will provide a general overview of the use of PIs in myeloma and AL amyloidosis, with particular emphasis on the limitations of such therapy.

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Abbreviations

AL:

Amyloidosis

ASCT:

Autologous stem cell transplant

BTZ:

Bortezomib

CFZ:

Carfilzomib

CR:

Complete response

DEX:

Dexamethasone

DLZ:

Delanzomib, CEP-18770

IMiDs:

Immunomodulatory drugs

IV:

Intravenously

IXZ:

Ixazomib, MLN-9708

LEN:

Lenalidomide

MEL:

Melphalan

MM:

Multiple myeloma

MRZ:

Marizomib, NPI-0052, salinosporamide A

OPZ:

Oprozomib, ONX-0912, PR-047

PAD:

BTZ + doxorubicin + DEX

PIs:

Proteasome inhibitors

PN:

Peripheral neuropathy

PR:

Partial response

SC:

Subcutaneously

UPS:

Ubiquitin-proteasome system

VAD:

Vincristine-adriamycin [doxorubicin]-dexamethasone

VGPR:

Very good partial response

VMP:

BTZ + MEL + PRED

VRD:

BTZ + LEN + DEX

VTD:

BTZ + THAL + DEX

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  1. Departments of Oncology and Medicine, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI, USA

    Jeffrey A. Zonder M.D.

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  1. Wayne State University, Detroit, Michigan, USA

    Q. Ping Dou

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Zonder, J.A. (2014). Proteasome Inhibitors in the Treatment of Multiple Myeloma and AL Amyloidosis. In: Dou, Q. (eds) Resistance to Proteasome Inhibitors in Cancer. Resistance to Targeted Anti-Cancer Therapeutics. Springer, Cham. https://doi.org/10.1007/978-3-319-06752-0_4

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