Abstract
This article presents a practical overview of the treatment of younger, newly diagnosed multiple myeloma patients, focusing on novel treatment strategies. With the introduction of effective new agents, multiple myeloma is one of the most active and changing fields in clinical oncology. In addition, monitoring technology has become reliable and practical. Achieving and sustaining minimal residual disease negativity (MRD– ), such as multiparameter flow cytometry (MFC) < 10−5, is one of the goals of therapy. MRD– is significantly associated with prolonged progression-free survival, whereas MRD persistence (MRD +) is an independent factor for poor progression-free survival. Evidence from several recent studies evaluating modern therapy has further supported the positive correlation between depth of response and outcomes. Multiple myeloma can become a chronic illness with sustained MRD– in a significant number of patients. Our ultimate hope is to leverage tumoricidal-immunomodulatory sequential therapies and to cure a subset of our patients.
Similar content being viewed by others
References
Suzuki K. Current therapeutic strategy for Multiple myeloma. J Clin Oncol. 2013;43:116–24.
Kim K, Lee JH, Kim JS, Min CK, Yoon SS, Shimizu K, et al. Clinical profiles of multiple myeloma in Asia–an Asian Myeloma Network study. Am J Hematol. 2014;89:751–6.
Barlogie B. Toward a cure for multiple myeloma? N Engl J Med. 1991;325:1304–6.
Barlogie B, Mitchell A, van Rhee F, Epstein J, Morgan GJ, Crowley J. Curing myeloma at last: defining criteria and providing the evidence. Blood. 2014;124:3043–51.
Katodritou E, Papadaki S, Konstantinidou P, Terpos E. Is it possible to cure myeloma without allogeneic transplantation? Transfus Apheres Sci. 2016;54:63–70.
Davies FE. Is molecular remission the goal of multiple myeloma therapy? ASH Educ Book. 2017;1:205–11.
Usmani SZ, Hoering A, Cavo M, Miguel JS, Goldschimdt H, Hajek R, et al. Clinical predictors of long-term survival in newly diagnosed transplant eligible multiple myeloma—an IMWG Research Project. Blood Cancer J. 2018;8:123–30.
Ravi P, Shaji K, Kumar SK, Cerhan JR, Maurer MJ, Dingli D, et al. Defining cure in multiple myeloma: a comparative study of outcomes of young individuals with myeloma and curable hematologic malignancies. Blood Cancer J. 2018;8:26–33.
Choudhry P, Galligan D, Wiita AP. Seeking convergence and cure with new myeloma therapies. Trends Cancer. 2018;4:567–82.
Durie BGM, Hoering A, Abidi MH, Rajkumar SV, Epstein J, Kahanic SP, et al. Bortezomib with lenalidomide and dexamethasone versus lenalidomide and dexamethasone alone in patients with newly diagnosed myeloma without intent for immediate autologous stem-cell transplant (SWOG S0777): a randomised, open-label, phase 3 trial. Lancet. 2017;389:519–27.
Attal M, Lauwers-Cances V, Hulin C, Leleu X, Caillot D, Escoffre M, et al. IFM 2009 Study: Lenalidomide, Bortezomib, and Dexamethasone with transplantation for Myeloma. N Engl J Med. 2017;376:1311–20.
Miyazaki K, Suzuki K. Poor mobilizer and its countermeasures. Transfus Apher Sci. 2018;57:623–7.
Dhakal B, Szabo A, Chhabra S, Hamadani M, D'Souza A, Usmani SZ, et al. Autologous transplantation for newly diagnosed multiple myeloma in the era of novel agent induction: a systematic review and meta-analysis. JAMA Oncol. 2018;4:343–50.
Cook G, Royle KL, O'Connor S, Cairns DA, Ashcroft AJ, Williams CD, et al. National Cancer Research Institute Haemato-oncology Clinical Studies Group: the effect of salvage autologous stem-cell transplantation on overall survival in patients with relapsed multiple myeloma (final results from BSBMT/UKMF Myeloma X Relapse [Intensive]): a randomised, open-label, phase 3 trial. Lancet Haematol. 2016;3:340–51.
Botta et al. Best of ASH. Monday, December 3, 2018 San Diego, Blood Cancer in press 2018.
Lokhorst HM, Plesner T, Laubach JP, Nahi H, Gimsing P, Hansson M, et al. Targeting CD38 with daratumumab monotherapy in multiple myeloma. N Engl J Med. 2015;373:1207–19.
Palumbo A, Chanan-Khan A, Weisel K, Nooka AK, Masszi T, Beksac M, et al. Daratumumab, bortezomib, and dexamethasone for multiple myeloma. N Engl J Med. 2016;375:754–66.
Dimopoulos MA, Oriol A, Nahi H, San-Miguel J, Bahlis NJ, Usmani SZ, et al. Daratumumab, lenalidomide, and dexamethasone for multiple myeloma. N Engl J Med. 2016;375:1319–31.
Suzuki K, Dimopoulos MA, Takezako N, Okamoto S, Shinagawa A, Matsumoto M, et al. Daratumumab, lenalidomide, and dexamethasone in East Asian patients with relapsed or refractory multiple myeloma: subgroup analyses of the phase 3 POLLUX study. Blood Cancer J. 2018;8:41.
Martin T, Baz R, Benson DM, et al. A phase 1b study of isatuximab plus lenalidomide and dexamethasone for relapsed/refractory multiple myeloma. Blood. 2017;129:3294–303.
Mikhael J, Richardson PG, Usmani SZ, Raje N, Bensinger W, Karanes C, et al. A phase 1b study of Isatuximab plus pomalidomide/dexamethasone in relapsed/refractory multiple myeloma. Blood. 2019;134:123–33.
Siegel DS, Dimopoulos MA, Ludwig H, Facon T, Goldschmidt H, Jakubowiak A, et al. Improvement in overall survival with carfilzomib, lenalidomide, and dexamethasone in patients with relapsed or refractory multiple myeloma. J Clin Oncol. 2018;36:728–34.
Moreau P, Mateos MV, Berenson JR, Weisel K, Lazzaro A, Song K, et al. Once weekly versus twice weekly carfilzomib dosing in patients with relapsed and refractory multiple myeloma (A.R.R.O.W): interim analysis results of a randomized, phase 3 study. Lancet Oncol. 2018;19:953–64.
Suzuki K, Ri M, Chou T, Sugiura I, Takezako N, Sunami K, et al. Carfilzomib, lenalidomide and dexamethasone in patients with heavily pretreated multiple myeloma: a phase 1 study in Japan. Cancer Sci. 2017;108:461–8.
Kikuchi J, Hori M, Iha H, Toyama-Sorimachi N, Hagiwara S, Kuroda Y, et al. Soluble SLAMF7 promotes the growth of myeloma cells via homophilic interaction with surface SLAMF7. Leukemia. 2020;34:180–95.
Lonial S, Dimopoulos M, Palumbo A, White D, Grosicki S, Spicka I, et al. Elotuzumab therapy for relapsed or refractory multiple myeloma. N Engl J Med. 2015;373:621–31.
Suzuki K, Sunami K, Ohashi K, Iida S, Mori T, Handa H, et al. Randomized phase 3 study of elotuzumab for relapsed or refractory multiple myeloma: ELOQUENT-2 Japanese patient subanalysis. Blood Cancer J. 2017;7:e540.
Dimopoulos MA, Lonial S, Betts KA, Chen C, Zichlin ML, Brun A, et al. Elotuzumab plus lenalidomide and dexamethasone in relapsed/refractory multiple myeloma: extended 4-year follow-up and analysis of relative progression-free survival from the randomized ELOQUENT-2 trial. Cancer. 2018;124:4032–43.
Dimopoulos MA, Dytfeld D, Grosicki S, Moreau P, Takezako N, Hori M, et al. Elotuzumab plus Pomalidomide and Dexamethasone for Multiple Myeloma. N Engl J Med. 2018;379:1811–22.
Moreau P, Masszi T, Grzasko N, Bahlis NJ, Hansson M, Pour L, et al. Oral ixazomib, lenalidomide, and dexamethasone for multiple myeloma. N Engl J Med. 2017;374:1621–34.
Suzuki K, Handa H, Chou T, Ishizawa K, Takubo T, Kase Y, et al. Phase 1 study of ixazomib alone or combined with lenalidomide-dexamethasone in Japanese patients with relapsed/refractory multiple myeloma. Int J Hematol. 2017;105:445–52.
Dimopoulos MA, Gay F, Schjesvold F, Beksac M, Hajek R, Weisel KC, et al. Oral ixazomib maintenance following autologous stem cell transplantation (TOURMALINE-MM3): a double-blind, randomized, placebo-controlled phase 3 trial. Lancet. 2019;393:253–64.
Avet-Loiseau H, Bahlis NJ, Chng WJ, Masszi T, Viterbo L, Pour L, et al. Ixazomib significantly prolongs progression-free survival in high-risk relapsed/refractory myeloma patients. Blood. 2017;130:2610–8.
Suzuki K, Matsue K, Sunami K. Pomalidomide + Bortezomib + Low-Dose Dexamethasone (PVd) in Japanese Patients Enrolled in OPTIMISMM. In: The 81th annual meeting of the JSH. 2019; OS1-70-4.
Garderet L, Kuhnowski F, Berge B, Roussel M, Escoffre-Barbe M, Lafon I, et al. Pomalidomide, cyclophosphamide, and dexamethasone for relapsed multiple myeloma. Blood. 2018;132:2555–633.
Richardson PG, Siegel DS, Vij R, Hofmeister CC, Baz R, Jagannath S, et al. Pomalidomide alone or in combination with low-dose dexamethasone in relapsed and refractory multiple myeloma: a randomized phase 2 study. Blood. 2014;123:1826–32.
Miguel JS, Weisel K, Moreau P, Lacy M, Song K, Delforge M, et al. Pomalidomide plus low-dose dexamethasone versus high dose dexamethasone alone for patients with relapsed and refractory multiple myeloma (MM-003): a randomized, open-label, phase 3 trial. Lancet Oncol. 2013;14:1055–66.
Moreau P, Attal M, Hulin C, Arnulf B, Belhadj K, Benboubker L, et al. Bortezomib, thalidomide, and dexamethasone with or without daratumumab before and after autologous stem-cell transplantation for newly diagnosed multiple myeloma (CASSIOPEIA): a randomized, open-label, phase 3 study. Lancet. 2019;10192:29–38.
Peter MV, Cesar R, Brandi R, Nitya N, Luciano JC, Yana L, et al. Efficacy and updated safety analysis of a safety run-in cohort from griffin, a phase 2 randomized study of Daratumumab (Dara), Bortezomib (V), Lenalidomide (R), and Dexamethasone (D; Dara‐Vrd) Vs. Vrd in patients (Pts) with Newly Diagnosed (ND) Multiple Myeloma (MM) Eligible for High-Dose Therapy (HDT) and Autologous Stem Cell Transplantation (ASCT). Blood. 2018;132:151.
Raje N, Berdeja J, Lin Y, Siegel D, Jagannath S, Madduri D, et al. Anti-BCMA CAR T-cell therapy bb2121 in relapsed or refractory multiple myeloma. N Engl J Med. 2019;380:1726–37.
Lakshman A, Singh PP, Rajkumar SV, Dispenzieri A, Lacy MQ, Gertz MA, et al. Efficacy of VDT PACE-like regimens in treatment of relapsed/refractory multiple myeloma. Am J Hematol. 2018;93:179–86.
Dhakal B, Vesole DH, Hari PN. Allogeneic stem cell transplantation for multiple myeloma: is there a future? Bone Marrow Transplant. 2016;51:492–500.
Kawamura K, Tsukada N, Kanda Y, Ishida T, Suzuki K, Ikeda T, et al. The role of allogeneic transplantation for multiple myeloma in the era of novel agents: a study from the Japanese Society of Myeloma. Biol Blood Marrow Transplant. 2018;24:1392–8.
Evens AM, Jovanovic BD, Su YC, Raisch DW, Ganger D, Belknap SM, et al. Rituximab associated hepatitis B virus (HBV) reactivation in lymphoproliferative diseases: meta-analysis and examination of FDA safety reports. Ann Oncol. 2011;22:1170–80.
Johnsrud AJ, Johnsrud JJ, Susanibar SA, Kamimoto JJ, Kothari A, Burgess M, et al. Infectious and immunological sequelae of daratumumab in multiple myeloma. Br J Haematol. 2019;185:187–9.
Siddiqui M, Rajkumar SV. The high cost of cancer drugs and what we can do about it. Mayo Clin Proc. 2012;87:935–43.
Ramsey S, Blough D, Kirchhoff A, Kreizenbeck K, Fedorenko C, Snell K, et al. Washington State cancer patients found to be at greater risk for bankruptcy than people without a cancer diagnosis. Health Affairs (Project Hope). 2013;32:1143–52.
Usmani SZ, Cavenagh JD, Belch AR, Hulin C, Basu S, White D, et al. Cost-effectiveness of lenalidomide plus dexamethasone versus bortezomib plus melphalan and prednisone in transplant-ineligible US patients with newly diagnosed multiple myeloma. J Med Econ. 2016;19:243–58.
MacEwan JP, Batt K, Yin W, Peneva D, Sison S, Vine S, et al. Economic burden of multiple myeloma among patients in successive lines of therapy in the United States. Leuk Lymphoma. 2018;59:941–9.
Fonseca R, Abouzaid S, Bonafede M, Cai Q, Parikh K, Cosler L, et al. Trends in overall survival and costs of multiple myeloma, 2000–2014. Leukemia. 2017;31:1915–21.
Walker BA, Mavrommatis K, Wardell CP, Ashby TC, Bauer M, Davies FE, et al. Identification of novel mutational drivers reveals oncogene dependencies in multiple myeloma. Blood. 2018;132:587–97.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
K. Suzuki received honoraria from Celgene, Takeda, ONO, Amgen, Novartis, Sanofi, Bristol-Myers Squibb, AbbVie and Janssen, and consulted for Amgen, Janssen, Takeda, and Celgene; received research funding from Bristol-Myers Squibb, Celgene and Amgen.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
About this article
Cite this article
Suzuki, K. Latest treatment strategies aiming for a cure in transplant-eligible multiple myeloma patients: how I cure younger MM patients with lower cost. Int J Hematol 111, 512–518 (2020). https://doi.org/10.1007/s12185-020-02841-w
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12185-020-02841-w