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Review
. 2017 Apr;92(4):578-598.
doi: 10.1016/j.mayocp.2017.01.003. Epub 2017 Mar 11.

Therapy for Relapsed Multiple Myeloma: Guidelines From the Mayo Stratification for Myeloma and Risk-Adapted Therapy

David Dingli  1 , Sikander Ailawadhi  2 , P Leif Bergsagel  3 , Francis K Buadi  4 , Angela Dispenzieri  4 , Rafael Fonseca  3 , Morie A Gertz  4 , Wilson I Gonsalves  4 , Susan R Hayman  4 , Prashant Kapoor  4 , Taxiarchis Kourelis  4 , Shaji K Kumar  4 , Robert A Kyle  4 , Martha Q Lacy  4 , Nelson Leung  5 , Yi Lin  4 , John A Lust  4 , Joseph R Mikhael  3 , Craig B Reeder  3 , Vivek Roy  2 , Stephen J Russell  4 , Taimur Sher  2 , A Keith Stewart  3 , Rahma Warsame  4 , Stephen R Zeldenrust  4 , S Vincent Rajkumar  4 , Asher A Chanan Khan  2
Affiliations
Review

Therapy for Relapsed Multiple Myeloma: Guidelines From the Mayo Stratification for Myeloma and Risk-Adapted Therapy

David Dingli et al. Mayo Clin Proc. 2017 Apr.

Abstract

Life expectancy in patients with multiple myeloma is increasing because of the availability of an increasing number of novel agents with various mechanisms of action against the disease. However, the disease remains incurable in most patients because of the emergence of resistant clones, leading to repeated relapses of the disease. In 2015, 5 novel agents were approved for therapy for relapsed multiple myeloma. This surfeit of novel agents renders management of relapsed multiple myeloma more complex because of the occurrence of multiple relapses, the risk of cumulative and emergent toxicity from previous therapies, as well as evolution of the disease during therapy. A group of physicians at Mayo Clinic with expertise in the care of patients with multiple myeloma regularly evaluates the evolving literature on the biology and therapy for multiple myeloma and issues guidelines on the optimal care of patients with this disease. In this article, the latest recommendations on the diagnostic evaluation of relapsed multiple myeloma and decision trees on how to treat patients at various stages of their relapse (off study) are provided together with the evidence to support them.

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Conflict of interest statement

Potential Competing Interests: Dr Dingli has received research funding from Amgen, Millenium/Takeda, and Karyopharm. Dr Ailawadhi has received grants and other support from Pharmacyclics, Takeda Oncology, and Amgen, outside the submitted work. Dr Bergsagel has received personal fees from Janssen, Incyte, Juno, and Kesios; grants from Novartis; and nonfinancial support from Millenium, Amgen, Celgene, and E. R. Squibb & Sons, outside the submitted work. Dr Dispenzieri has received grants from Pfizer, Celgene, Takeda, and Alnylam and nonfinancial support from Janssen and Prothena, outside the submitted work. Dr Gertz has received grants from IONIS, Prothena Therapeutics, Annexon Biosciences, Novartis, and Alnylam Pharmaceuticals; personal fees from Celgene, Research To Practice, Med Learning Group, National Cancer Institute at Frederick, Sandoz Inc. (a Novartis Company), GlaxoSmithK-line, outside the submitted work. Dr Kapoor has received research funding from Takeda, Celgene, and Amgen. Dr Kumar has received consultancy fees from Merck, Millennium/Takeda, Celgene, Sanofi/Genzyme, Amgen, Janssen and Glycomimetics; speakers’ bureaus fees from Skyline Diagnostics, Noxxon, and Kesios. Dr Lacy has received grants from Celgene, outside the submitted work.

Figures

FIGURE 1
FIGURE 1
MSMART risk stratification in relapsed multiple myeloma. ASCT = autologous stem cell transplant; FISH = fluorescence in situ hybridization; GEP = gene expression profiling; MSMART = Mayo Stratification for Myeloma and Risk-Adapted Therapy.
FIGURE 2
FIGURE 2
Therapy for multiple myeloma at first relapse. The approach depends on the biology of the relapse (indolent vs aggressive), the performance status of the patient, molecular features of the disease, and the therapeutic history. ASCT = autologous stem cell transplant; DRd = dar-atumumab, lenalidomide, and dexamethasone; DVd = daratumumab, bortezomib, and dexamethasone; ERd = elotuzumab, lenalidomide, and dexamethasone; ICd = ixazomib, cyclophosphamide, and dexamethasone; IRd = ixazomib, lenalidomide, and dexamethasone; KPd = carfilzomib, pomalidomide, and dexamethasone; KRd = carfilzomib, lenalidomide, and dexamethasone.
FIGURE 3
FIGURE 3
Therapy for second or subsequent relapse of multiple myeloma. The decision on which agents to use depends on the therapeutic history and response to previous agents. Triple combination therapy is preferred. ASCT = autologous stem cell transplant; DPCd = daratumumab, pomalidomide, cyclophosphamide, and dexamethasone; DPd = daratumumab, pomalidomide, and dexamethasone; DRd = daratumumab, lenalidomide, and dexamethasone; DVd = daratumumab, bortezomib, and dexamethasone; IMiD = immunomodulatory drug; KPd = carfilzomib, pomalidomide, and dexamethasone; KRd = carfilzomib, lenalidomide, and dexamethasone; PI = proteasome inhibitor.
FIGURE 4
FIGURE 4
Patients with quadruple refractory disease have limited treatment options. If eligible, patients should be considered for ASCT. ASCT = autologous stem cell transplant; VDT-PACE = bortezomib, dexamethasone, thalidomide, cisplatin, doxorubicin, cyclophosphamide, and etoposide.
FIGURE 5
FIGURE 5
Therapy for secondary plasma cell leukemia or extramedullary multiple myeloma. Fit patients should receive intensive chemotherapy and consolidation by ASCT. Frail patients can be considered for an anthracycline- or daratumumab-based regimen. ASCT = autologous stem cell transplant; CVAD = cyclophosphamide, vincristine, doxorubicin, and dexamethasone; VDT-PACE = bortezomib, dexamethasone, thalidomide, cisplatin, doxorubicin, cyclophosphamide, and etoposide.
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References

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