A myeloma multiplex kezelése az elmúlt évtizedben óriásit változott. Mind a kemoterápiás protokollok, mind a szupportív kezelés nagy fejlődésen ment át, amióta a legutóbbi magyar ajánlás megjelent. A betegek egyre nagyobb része ér el tartós választ, és mind többük számára van talán esély a gyógyulásra is. Az összefoglaló célja, hogy az utóbbi évek eredményeit is beépítve, az érvényes nemzetközi ajánlásokat a magyar viszonyok sajátosságaihoz adaptálva segítse a betegek leghatékonyabb kezelését. Orv. Hetil., 2016, 157(4), 123–137.
Engelhardt, M., Terpos, E., Kleber, M., et al.: European Myeloma Network recommendations on the evaluation and treatment of newly diagnosed patients with multiple myeloma. Haematologica, 2014, 99(2), 232–242.
Radványi, G., Mikala, G., Masszi, T., et al.: Diagnosis and treatment of multiple myeloma (MM). In: Lehoczky, D. (ed.): Current treatment of hematologic diseases. Treatment guideline of the Hungarian Professional Board of Transfusion and Hematology. [A myeloma multiplex (MM) diagnózisa és kezelése. In: Lehoczky, D. (szerk.): Hematológiai betegségek korszerű kezelése. A Magyar Transzfuziológiai és Hematológiai Szakmai Kollégium és a Tudományos Társaság kezelési irányelvei.] Zafír Press, Budapest, 2014. [Hungarian]
Rajkumar, S. V., Dimopoulos, M. A., Palumbo, A., et al.: International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol., 2014, 15(12), e538–e548.
Kyle, R. A., Gertz, M. A., Witzig, T. E., et al.: Review of 1027 patients with newly diagnosed multiple myeloma. Mayo Clin. Proc., 2003, 78(1), 21–33.
Fonseca, R., Bergsagel, P. L., Drach J., et al.: International Myeloma Working Group molecular classification of multiple myeloma: spotlight review. Leukemia, 2009, 23(12), 2210–2221.
Klein, B., Seckinger, A., Moehler, T., et al.: Molecular pathogenesis of multiple myeloma: chromosomal aberrations, changes in gene expression, cytokine networks and the bone marrow microenvironment. Recent Results Cancer Res., 2011, 183, 39–86.
Bergsagel, P. L., Kuehl, W. M., Zhan, F., et al.: Cyclin D dysregulation: an early and unifying pathogenic event in multiple myeloma. Blood, 2005, 106(1), 296–303.
Chapman, M. A., Lawrence, M. S., Keats, J. J., et al.: Initial genome sequencing and analysis of multiple myeloma. Nature, 2011, 471(7339), 467–472.
Lohr, J. G., Stojanov, P., Carter, S. L., et al.: Widespread genomic heterogeneity in multiple myeloma: implications for targeted therapy. Cancer Cell, 2014, 25(1), 91–101.
Egan, J. B., Shi, C. X., Tembe, W., et al.: Whole genome sequencing of multiple myeloma from diagnosis to plasma cell leukemia reveals genomic initiating events, evolution and clonal tides. Blood, 2012, 120(5), 1060–1066.
Broyl, A., Hose, D., Lokhorst, H., et al.: Gene expression profiling for molecular classification of multiple myeloma in newly diagnosed patients. Blood, 2010, 116(14), 2543–2553.
Walker, B. A., Boyle, E. M., Wardell, C. P., et al.: Mutational spectrum, copy number changes, and outcome: Results of a sequencing study of patients with newly diagnosed myeloma. J. Clin. Oncol., 2015, 33(33), 3911–3920.
Lionetti, M., Barbieri, M., Todoerti K., et al.: Molecular spectrum of BRAF, NRAS and KRAS gene mutations in plasma cell dyscrasias: implication of MEK-ERK pathway activation. Oncotarget, 2015, 6(27), 24205–24217.
Seckinger, A., Hose, D.: Dissecting the clonal architecture of multiple myeloma. 20th Congress of the European Hematology Association, Vienna, Austria. Haematologica, 2015, 9, 173–179.
Walker, B. A., Wardell, C. P., Melchor, L., et al.: Intraclonal heterogeneity is a critical early event in the development of myeloma and precedes the development of clinical symptoms. Leukemia, 2014, 28(2), 384–390.
Keats, J. J., Chesi, M., Egan, J. B., et al.: Clonal competition with alternating dominance in multiple myeloma. Blood, 2012, 120(5), 1067–1076.
Melchor, L., Brioli, A., Wardell, C. P., et al.: Single-cell genetic analysis reveals the composition of initiating clones and phylogenetic patterns of branching and parallel evolution in myeloma. Leukemia, 2014, 28(8), 1705–1715.
Morgan, G. J., Walker, B. A., Davies, F. E., et al.: The genetic architecture of multiple myeloma. Nat. Rev. Cancer, 2012, 12(5), 335–348.
Bianchi, G., Ghobrial, I. M.: Biological and clinical implications of clonal heterogeneity and clonal evolution in multiple myeloma. Curr. Cancer Ther. Rev., 2014, 10(2), 70–79.
Kyle, R. A., Rajkumar, S. V.: Multiple myeloma. N. Engl. J. Med., 2004, 351(18), 1860–1873.
Raja, K. R., Kovarova, L., Hajek, R.: Review of phenotypic markers used in flow cytometric analysis of MGUS and MM and applicability of flow cytometry in other plasma cell disorders. Br. J. Haematol., 2010, 149(3), 334–351.
Fonseca, R., Monge, J., Dimopoulos, M. A.: Staging and prognostication of multiple myeloma. Expert Rev. Hematol., 2014, 7(1), 21–31.
Jenner, E.: Serum free light chains in clinical laboratory diagnostics. Clin. Chim. Acta, 2014, 427, 15–20.
Palumbo, A., Avet-Loiseau, H., Oliva, S., et al.: Revised International Staging System for multiple myeloma: A report from International Myeloma Working Group. J. Clin. Oncol., 2015, 33(26), 2863–2869.
Derlin, T., Bannas, P.: Imaging of multiple myeloma: current concepts. World J. Orthop., 2014, 5(3), 272–282.
Gleeson, T. G., Moriarty, J., Shortt, C. P., et al.: Accuracy of whole-body low-dose multidetector CT (WBLDCT) versus skeletal survey in the detection of myelomatous lesions and correlation of disease distribution with whole body MRI (WBMRI). Skeletal Radiol., 2009, 38(3), 225–236.
Hanrahan, C. J., Christensen, C. R., Crim, J. R.: Current concepts in the evaluation of multiple myeloma with MR imaging and FDG PET/CT. Radiographics, 2010, 30(1), 127–142.
Mikala, G., Jákó, J., Vályi-Nagy, I.: The role of thalidomide in the treatment of multiple myeloma. [A thalidomid szerepe a myeloma multiplex gyógykezelésében.] Orv. Hetil., 2001, 142(33), 1789–1798. [Hungarian]
Mikala, G., Jákó, J., Vályi-Nagy, I.: Proteasome inhibition: a new therapeutic approach for the treatment of multiple myeloma. [Proteaszómagátlás: új terápiás lehetőség myeloma multiplex kezelésére.] Orv. Hetil., 2004, 145(2), 67–74. [Hungarian]
Varga, G., Mikala, G., Andrikovics, H., et al.:NFKB1 -94ins/delATTG polymorphism is a novel prognostic marker in first linetreated multiple myeloma. Br. J. Haematol., 2015, 168(5), 679–688.
Moreau, P., Pylypenko, H., Grosicki, S., et al.: Subcutaneous versus intravenous administration of bortezomib in patients with relapsed multiple myeloma: a randomised, phase 3, non-inferiority study. Lancet Oncol., 2011, 12(5), 431–440.
Mikala, G., Bátai, Á., Ceglédi, A., et al.: Our experience with bortezomib-based therapy of multiple myeloma based on the first 60 patients. [A myeloma multiplex bortezomibalapú kezelése – Hazai tapasztalatok az első 60 beteg adatainak tükrében.] LAM, 2007, 17(1), 26–34. [Hungarian]
Zimmerman, T. M., Griffith, K. A., Jasielec, J.: Phase II MMRC trial of extended treatment with carfilzomib, lenalidomide, and dexamethasone plus autologous stem cell transplantation in newly diagnosed multiple myeloma. J. Clin. Oncol., 2015, 33(Suppl.), abstr. 8510.
Lokhorst, H. M., Laubach, J., Nahi, H.: Dose-dependent efficacy of daratumumab (DARA) as monotherapy in patients with relapsed or refractory multiple myeloma (RR MM). J. Clin. Oncol., 2014, 32(Suppl.), abstr. 8513.
Lonial, S., Dimopoulos, M. A., Palumbo, A.: ELOQUENT-2: A phase III, randomized, open-label study of lenalidomide/dexamethasone with/without elotuzumab in patients with relapsed/refractory multiple myeloma. J. Clin. Oncol., 2015, 33(Suppl.), abstr. 8508.
Gorgun, G., Samur, M. K., Cowens, K. B., et al.: Lenalidomide enhances immune checkpoint blockade induced immune response in multiple myeloma. Clin. Cancer Res., 2015, 21(20), 4607–4618.
Rosiñol, L., Oriol, A., Teruel, A. I.: Superiority of bortezomib, thalidomide, and dexamethasone (VTD) as induction pretransplantation therapy in multiple myeloma: a randomized phase 3 PETHEMA/GEM study. Blood, 2012, 120(8), 1589–1596.
Reeder, C. B., Reece, D. E., Kukreti, V., et al.: Cyclophosphamide, bortezomib and dexamethasone induction for newly diagnosed multiple myeloma: high response rates in a phase II clinical trial. Leukemia, 2009, 23(7), 1337–1341.
Sonneveld, P., Schmidt-Wolf, I. G., van der Holt, B., et al.: Bortezomib induction and maintenance treatment in patients with newly diagnosed multiple myeloma: results of the randomized phase III HOVON-65/GMMG-HD4 trial. J. Clin. Oncol., 2012, 30(24), 2946–2955.
Leiba, M., Kedmi, M., Duek, A., et al.: Bortezomib-cyclophosphamide-dexamethasone (VCD) versus bortezomib-thalidomide-dexamethasone (VTD) -based regimens as induction therapies in newly diagnosed transplant eligible patients with multiple myeloma: a meta-analysis. Br. J. Haematol., 2014, 166(5), 702–710.
Painuly, U., Kumar, S.: Efficacy of bortezomib as first-line treatment for patients with multiple myeloma. Clin. Med. Insights Oncol., 2013, 7, 53–73.
Palumbo, A., Bringhen, S., Mateos, M. V., et al.: Geriatric assessment predicts survival and toxicities in elderly myeloma patients: an International Myeloma Working Group report. Blood, 2015, 125(13), 2068–2074.
Rajkumar, S. V., Jacobus, S., Callander N. S., et al.: Lenalidomide plus high-dose dexamethasone versus lenalidomide plus low-dose dexamethasone as initial therapy for newly diagnosed multiple myeloma: an open-label randomised controlled trial. Lancet Oncol., 2010, 11(1), 29–37.
Richardson, P. G., Weller, E., Lonial, S., et al.: Lenalidomide, bortezomib, and dexamethasone combination therapy in patients with newly diagnosed multiple myeloma. Blood, 2010, 116(5), 679–686.
San Miguel, J. F., Schlag, R., Khuageva, N. K., et al.: Bortezomib plus melphalan and prednisone for initial treatment of multiple myeloma. N. Engl. J. Med., 2008, 359(9), 906–917.
Morgan, G. J., Davies, F. E., Gregory, W. M., et al.: Long-term follow-up of MRC Myeloma IX trial: Survival outcomes with bisphosphonate and thalidomide treatment. Clin. Cancer Res., 2013, 19(21), 6030–6038.
Facon, T., Mary, J. Y., Hulin, C., et al.: Melphalan and prednisone plus thalidomide versus melphalan and prednisone alone or reduced-intensity autologous stem cell transplantation in elderly patients with multiple myeloma (IFM 99-06): a randomised trial. Lancet, 2007, 370(9594), 1209–1218.
Grey-Davies, E., Bosworth, J. L., Boyd, K. D., et al.: Bendamustine, thalidomide and dexamethasone is an effective salvage regimen for advanced stage multiple myeloma. Br. J. Haematol., 2012, 156(4), 552–555.
Lentzsch, S., O’Sullivan, A., Kennedy, R. C.: Combination of bendamustine, lenalidomide, and dexamethasone (BLD) in patients with relapsed or refractory multiple myeloma is feasible and highly effective: results of phase 1/2 open-label, dose escalation study. Blood, 2012, 119(20), 4608–4613.
Bringhen, S., Petrucci, M. T., Larocca, A., et al.: Carfilzomib, cyclophosphamide, and dexamethasone in patients with newly diagnosed multiple myeloma: a multicenter, phase 2 study. Blood, 2014, 124(1), 63–69.
Stewart, A. K., Rajkumar, S. V., Dimopoulos, M. A., et al.: Carfilzomib, lenalidomide, and dexamethasone for relapsed multiple myeloma. N. Engl. J. Med., 2015, 372(2), 142–152.
Kumar, S. K., Berdeja, J. G., Niesvizky, R., et al.: Safety and tolerability of ixazomib, an oral proteasome inhibitor, in combination with lenalidomide and dexamethasone in patients with previously untreated multiple myeloma: an open-label phase 1/2 study. Lancet Oncol., 2014, 15(13), 1503–1512.
Richardson, P. G., Siegel, D. S., Vij, R., 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(12), 1826–1832.
Barlogie, B., Velasquez, W. S., Alexanian, R., et al.: Etoposide, dexamethasone, cytarabine and cisplatin in vincristine, doxorubicin and dexamethasone-refractory myeloma. J. Clin. Oncol., 1989, 7(10), 1514–1517.
Barlogie, B., Anaissie, E., van Rhee, F., et al.: Incorporating bortezomib into upfront treatment for multiple myeloma: early results of total therapy 3. Br. J. Haematol., 2007, 138(2), 176–185.
Pozzi, S., Marcheselli, L., Bari, A., et al.: Survival of multiple myeloma patients in the era of novel therapies confirms the improvement in patients younger than 75 years: a population-based analysis. Br. J. Haematol., 2013, 163(1), 40–46.
Mikhael, J. R., Dingli, D., Roy, V., et al.: Management of newly diagnosed symptomatic multiple myeloma: updated Mayo Stratification of Myeloma and Risk-Adapted Therapy (mSMART) consensus guidelines 2013. Mayo Clin. Proc., 2013, 88(4), 360–376.
Varga, G., Reményi, P., Mikala, G., et al.: Single center experience with early versus late autologous stem cell transplantation in multiple myeloma. Haematologica, 2015, 100, 652.
Masszi, T.: Hemopoietic stem cell transplantation in Hungary: activity and indications. [Hemopoietikus őssejt-transzplantáció Magyarországon: aktivitás és indikációk.] Transzfúzió, 2000, 33(2), 67–71. [Hungarian]
Cook, G., Williams, C., Brown, J. M., et al.: High-dose chemotherapy plus autologous stem-cell transplantation as consolidation therapy in patients with relapsed multiple myeloma after previous autologous stem-cell transplantation (NCRI Myeloma X Relapse [Intensive trial]): a randomised, open-label, phase 3 trial. Lancet Oncol., 2014, 15(8), 874–885.
Vesole, D. H., Zhang, L., Flomenberg, N., et al.: A phase II trial of autologous stem cell transplantation followed by mini-allogeneic stem cell transplantation for the treatment of multiple myeloma: an analysis of Eastern Cooperative Oncology Group ECOG E4A98 and E1A97. Biol. Blood Marrow Transplant., 2009, 15(1), 83–91.
Rajkumar, S. V., Harousseau, J. L., Durie, B., et al.: Consensus recommendations for the uniform reporting of clinical trials: report of the International Myeloma Workshop Consensus Panel 1. Blood, 2011, 117(18), 4691–4695.
Chen, C. I., Masih-Khan, E., Jiang, H., et al.: Central nervous system involvement with multiple myeloma: long term survival can be achieved with radiation, intrathecal chemotherapy, and immunomodulatory agents. Br. J. Haematol., 2013, 162(4), 483–488.
Ashley, C., Dunleavey, A. (eds.): The renal drug handbook. Radcliffe Publishing, London, 2014.
Sinkó, J., Cser, V., Konkoly Thege, M., et al.: Gram-negative bacteremia in neutropenic patients with hematologic disorders. Experiences with prophylactic use of fluoroquinolones. [Gram-negatív bacteriaemia neutropeniás hematológiai betegekben. Tapasztalatok fluorokinolonprofilaxis alkalmazása kapcsán.] Orv. Hetil., 2011, 152(27), 1063–1067. [Hungarian]
Snowden, J. A., Ahmedzai, S. H., Ashcroft, J., et al.: Guidelines for supportive care in multiple myeloma 2011. Br. J. Haematol., 2011, 154(1), 76–103.