Rezidivtherapie des Multiplen Myeloms – Individualisierte Konzepte aus dem Arsenal vielfältiger Optionen

Abstract

The prognosis of patients with multiple myeloma has improved significantly over the past 20 years. However, the patient population in the relapse situation is very heterogeneous due to increasing age and the previous course of the disease and therapy. In particular, the approval of new targeted substances offers numerous treatment options that can be adapted to the individual situation.

In relapsed multiple myeloma, disease- and patient-specific factors must be considered for an individually adapted therapy. Suitable patients can also receive an autologous stem cell transplant (ASCT) or, in the case of early relapse after ASCT, an allogenic stem cell transplant, if possible as part clinical studies. Proteasome or immunomodulator-based triple combinations are the standard in recurrence. In frail patients, a combination of two can also be used. The new substances also offer very good therapeutic options for high-risk cytogenetics or renal insufficiency. The monoclonal antibodies Daratumumab and Elotuzumab are well tolerated except for infusion reactions and are highly effective in various combinations, even in high-risk cytogenetics.

Die Prognose von Patienten mit Multiplem Myelom hat sich in den letzten 20 Jahren deutlich verbessert. Das Patientenkollektiv in der Rezidivsituation ist jedoch aufgrund des zunehmenden Alters und des vorangegangenen Krankheits- und Therapieverlaufs sehr heterogen. Insbesondere durch die Zulassung neuer zielgerichteter Substanzen bieten sich zahlreiche Therapieoptionen, die an die individuelle Situation angepasst werden können.

Schlüsselwörter

Rückfall - patientenspezifische Faktoren - Hochrisiko-Zytogenetik - 3-fach-Kombinationen - monoklonale Antikörper

Key words

relapse - patient-specific factors - high-risk cytogenetics - triple combinations - monoclonal antibodies

Publication History

Article published online:
17 June 2020

• Literatur

• 1 Larocca A, Dold SM, Zweegman S. et al Patient-centered practice in elderly myeloma patients: An overview and consensus from the European Myeloma Network (EMN). Leukemia 2018; 32: 1697-1712 . doi:10.1038/s41375-018-0142-9
• 2 Wörmann B, Driessen C, Einsele H. et al Onkopedia Leitlinie Multiples Myelom. Stand: Mai 2018. Im Internet: https://www.onkopedia.com/de/onkopedia/guidelines/multiples-myelom/@@guideline/html/index.html
• 3 Moreau P, San Miguel J, Sonneveld P. et al Multiple myeloma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2017; 28 (Suppl. 04) iv52-iv61 . doi:10.1093/annonc/mdx096
• 4 Kumar SK, Callander NS, Alsina M. et al NCCN Guidelines Insights: Multiple Myeloma, Version 3.2018. J Natl Compr Canc Netw 2018; 16: 11-20 . doi:10.6004/jnccn.2018.0002
• 5 Einsele H, Schafer HJ, Hebart H. et al Follow-up of patients with progressive multiple myeloma undergoing allografts after reduced-intensity conditioning. Br J Haematol 2003; 121: 411-418 . doi:10.1046/j.1365-2141.2003.04299
• 6 Sonneveld P, Avet-Loiseau H, Lonial S. et al Treatment of multiple myeloma with high-risk cytogenetics: a consensus of the International Myeloma Working Group. Blood 2016; 127: 2955-2962 . doi:10.1182/blood-2016-01-631200
• 7 Stewart AK, Rajkumar SV, Dimopoulos MA. et al Carfilzomib, lenalidomide, and dexamethasone for relapsed multiple myeloma. N Engl J Med 2015; 372: 142-152 . doi:10.1056/NEJMoa1411321
• 8 Dimopoulos MA, Moreau P, Palumbo A. et al Carfilzomib and dexamethasone versus bortezomib and dexamethasone for patients with relapsed or refractory multiple myeloma (ENDEAVOR): a randomised, phase 3, open-label, multicentre study. Lancet Oncol 2016; 17: 27-38 . doi:10.1016/S1470-2045(15)00464-7
• 9 Moreau P, Masszi T, Grzasko N. et al Oral Ixazomib, Lenalidomide, and Dexamethasone for Multiple Myeloma. N Engl J Med 2016; 374: 1621-1634 . doi:10.1056/NEJMoa1516282
• 10 Miguel JS, Weisel K, Moreau P. et al 2. Pomalidomide plus low-dose dexamethasone versus high-dose dexamethasone alone for patients with relapsed and refractory multiple myeloma (MM-003): a randomised, open-label, phase 3 trial. Lancet Oncol 2013; 14: 1055-1066 . doi:10.1016/S1470-2045(13)70380-2
• 11 Richardson PG, Oriol A, Beksac M. et al Pomalidomide, bortezomib, and dexamethasone for patients with relapsed or refractory multiple myeloma previously treated with lenalidomide (OPTIMISMM): a randomised, open-label, phase 3 trial. Lancet Oncol 2019; 20: 781-794 . doi:10.1016/S1470-2045(19)30152-4
• 12 San-Miguel JF, Hungria VT, Yoon SS. et al Panobinostat plus bortezomib and dexamethasone versus placebo plus bortezomib and dexamethasone in patients with relapsed or relapsed and refractory multiple myeloma: a multicentre, randomised, double-blind phase 3 trial. Lancet Oncol 2014; 15: 1195-1206 . doi:10.1016/S1470-2045(14)70440-1
• 13 Richardson PG, Hungria VT, Yoon SS. et al Panobinostat plus bortezomib and dexamethasone in previously treated multiple myeloma: outcomes by prior treatment. Blood 2016; 127: 713-721 . doi:10.1182/blood-2015-09-665018
• 14 Palumbo A, Chanan-Khan A, Weisel K. et al Daratumumab, Bortezomib, and Dexamethasone for Multiple Myeloma. N Engl J Med 2016; 375: 754-766 . doi:10.1056/NEJMoa1606038
• 15 Dimopoulos MA, Oriol A, Nahi H. et al Daratumumab, Lenalidomide, and Dexamethasone for Multiple Myeloma. N Engl J Med 2016; 375: 1319-1331
• 16 Usmani SZ, Quach H, Mateos MV. et al Carfilzomib, Dexamethasone, and Daratumumab Versus Carfilzomib and Dexamethasone for the Treatment of Patients with Relapsed or Refractory Multiple Myeloma (RRMM). Blood 2019; 134 (Suppl. 02) LBA-6 . doi:10.1182/blood-2019-132629
• 17 Lonial S, Dimopoulos M, Palumbo A. et al Elotuzumab Therapy for Relapsed or Refractory Multiple Myeloma. N Engl J Med 2015; 373: 621-631 . doi:10.1056/NEJMoa1505654
• 18 Dimopoulos MA, Dytfeld D, Grosicki S. et al Elotuzumab plus Pomalidomide and Dexamethasone for Multiple Myeloma. N Engl J Med 2018; 379: 1811-1822 . doi:10.1056/NEJMoa1805762
• 19 Ghosh A, Mailankody S, Giralt SA. et al CAR T cell therapy for multiple myeloma: where are we now and where are we headed?. Leuk Lymphoma 2018; 59: 2056-2067 . doi:10.1080/10428194.2017.1393668
• 20 Lonial S, Amatangelo M, Popat R. et al Translational and Clinical Evidence of a Differentiated Profile for the Novel CELMoD, Iberdomide (CC-220). Blood 2019; 134 (Suppl. 01) 3119 . doi:10.1182/blood-2019-124298
• 21 Attal M, Richardson PG, Rajkumar SV. et al Isatuximab plus pomalidomide and low-dose dexamethasone versus pomalidomide and low-dose dexamethasone in patients with relapsed and refractory multiple myeloma (ICARIA-MM). Lancet 2019; 394: 2096-2107 . doi:10.1016/S0140-6736(19)32556-5
• 22 Chari A, Vogl DT, Gavriatopoulou M. et al Oral Selinexor-Dexamethasone for Triple-Class Refractory Multiple Myeloma. N Engl J Med 2019; 381: 727-738 . doi:10.1056/NEJMoa1903455