Management der Polyneuropathie beim Multiplen Myelom unter der Therapie mit Bortezomib: Empfehlungen aus klinischen Erfahrungen

Zusammenfassung

Die bortezomibinduzierte periphere Neuropathie (PNP) beim Multiplen Myelom (MM) kann sich schnell entwickeln und fortschreiten. Durch rasches therapeutisches Eingreifen kann das Auftreten neuropathischer Schmerzen und die Weiterentwicklung zu höhergradigen Formen der PNP möglicherweise vermieden werden. Eine Expertenrunde aus Hämatologen und Neurologen gibt diesbezüglich Empfehlungen basierend auf ihren Erfahrungen. Als Basisuntersuchung für eine Verlaufsbeurteilung des Schweregrades einer PNP sind Erhebungen des neurologischen Ausgangsbefundes und neurologische Untersuchungen während der Bortezomibtherapie erforderlich. Diese können vom Hämatologen selbst durchgeführt werden, wobei ein Selbstauskunftsbogen des Patienten als wichtiges Instrument angesehen werden kann. Tritt eine bortezomibassoziierte PNP auf, ist die Therapie zu modifizieren. Internationale Experten benutzen hierzu unterschiedliche Schemata, evidenz-basierte Daten sind spärlich. Bei Polyneuropathien, die durch Komorbiditäten verursacht werden, kann schon vor Therapiebeginn eine Reduktion der Dosis überlegt werden. Die Behandlung der PNP selbst wird in diesem Manuskript erörtert. Medikamentöse und nicht medikamentöse Optionen können häufig zu einer deutlichen Symptomerleichterung oder -kupierung der PNP-Beschwerden führen.

Abstract

Bortezomib-induced peripheral neuropathy (PNP) in multiple myeloma (MM) can develop and progress rapidly. Rapid therapeutic intervention can possibly avoid the occurrence of neuropathic pain and the progression to higher grades of PNP. A group of experts consisting of haematologists and neurologists is issuing practice recommendations based on their experiences. The initial neurological assessment and neurological examinations during Bortezomib-therapy provide a basis for monitoring the patient. These examinations can be carried out by the haematologist. An important instrument is a questionnaire for the patients. If additional diagnostic workup is needed, consultation of a neurologist may be advantageous to fully evaluate the severity and type of PNP. If PNP develops, the therapy with Bortezomib has to be modified. International experts use different schemes, however, evidence based studies comparing these schemes are rare. In case of polyneuropathies caused by comorbidities, the possibility of dose reduction should be checked already prior to treatment initiation. Treatment of the PNP itself is discussed in the manuscript. Drug based as well as non-drug based therapies can often lead to significant improvement or even resolution of PNP symptoms.

Schlüsselwörter

Bortezomib - multiples Myelom - periphere Neuropathie - Polyneuropathie - PNP - Nerven - Prävention

Key words

Bortezomib - multiple myeloma - nerve damage - peripheral neuropathy - polyneuropathy

Literatur

• 1 Richardson P G, Xie W, Mitsiades C et al. Single-Agent Bortezomib in Previously Untreated Multiple Myeloma: Efficacy, Characterization of Peripheral Neuropathy, and Molecular Correlations With Response and Neuropathy.  J Clin Oncol. 2009;  27 (21) 3518-3525
• 2 San M iguel JF, 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
• 3 Richardson P G, Sonneveld P, Schuster M W et al. Reversibility of symptomatic peripheral neuropathy with bortezomib in the phase III APEX trial in relapsed multiple myeloma: impact of a dose-modification guideline.  Br J Haematol. 2009;  144 (6) 895-903
• 4 Mileshkin L, Stark R, Day B et al. Development of Neuropathy in Patients With Myeloma Treated With Thalidomide: Patterns of Occurrence and the Role of Electrophysiologic Monitoring.  J Clin Oncol. 2006;  24 (27) 4507-4514
• 5 Dispenzieri A, Kyle R A. Neurological aspects of multiple myeloma and related disorders.  Best Practice & Research Clinical Haematology. 2005;  18 (4) 673-688
• 6 Silberman J, Lonial S. Review of peripheral neuropathy in plasma cell disorders.  Hematol Oncol. 2008;  26 (2) 55-65
• 7 Argyriou A A, Iconomou G, Kalofonos H P. Bortezomib-induced peripheral neuropathy in multiple myeloma: a comprehensive review of the literature.  Blood. 2008;  112 1593-1599
• 8 Cata J P, Weng H R, Burton A W et al. Quantitative sensory findings in patients with bortezomib-induced pain.  J Pain. 2007;  8 (4) 296-306
• 9 Mileshkin L, Prince H M. The troublesome toxicity of peripheral neuropathy with thalidomide.  Leuk Lymphoma. 2006;  47 (11) 2276-2279
• 10 Chaudhry V, Cornblath D R, Corse A et al. Thalidomide-induced neuropathy.  Neurology. 2002;  59 (12) 1872-1875
• 11 Richardson P G, Chanan-Khan A, Schlossman R et al. A Multicenter Phase II Trial of Bortezomib in Patients with Previously Untreated Multiple Myeloma: Efficacy with Manageable Toxicity in Patients with Unexpectedly High Rates of Baseline Peripheral Neuropathy.  Blood. 2005;  106 716a
• 12 Koeppen S. Tumortherapie-bedingte Neuropathie.  Onkologe. 2009;  15 142-149
• 13 Mohty B, El-Cheikh J, Yakoub-Agha I et al. Peripheral neuropathy and new treatments for multiple myeloma: background and practical recommendations.  Haematologica. 2010;  95 (2) 311-319
• 14 Calhoun E A, Fishman D A, Roland P Y et al. Validity and selective sensitivity of the FACT/GOG-Ntx.  Proceedings of the American Society of Clinical Oncology. 2000;  19 446a
• 15 FACT/GOG-Ntx .Functional Assessment of Chronic Illness Therapy (FACIT) Measurement System. http://www.facit.org/qview/qlist.aspx 22 – 03 – 2010
• 16 Common Terminology Criteria for Adverse Events v4.0 22.3.2010 http://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.02_2009–09–15_QuickReference_5x7.pdf 22 – 03 – 2010
• 17 Velcade(R) Summary of Product Characteristics. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000539/WC500048471.pdf 11 - 08-2010
• 18 Richardson P G, Sonneveld P, Schuster M W et al. Bortezomib or high-dose dexamethasone for relapsed multiple myeloma.  N Engl J Med. 2005;  352 (24) 2487-2498
• 19 Palumbo A, Bringhen S, Rossi D et al. A Prospective, Randomized, Phase III Study of Bortezomib, Melphalan, Prednisone and Thalidomide (VMPT) Versus Bortezomib, Melphalan and Prednisone (VMP) in Elderly Newly Diagnosed Myeloma Patients.  ASH Annual Meeting Abstracts. 2008;  112 (11) 652
• 20 Mateos M V, Oriol A, Martinez-Lopez J et al. Bortezomib, melphalan, and prednisone versus bortezomib, thalidomide, and prednisone as induction therapy followed by maintenance treatment with bortezomib and thalidomide versus bortezomib and prednisone in elderly patients with untreated multiple myeloma: a randomised trial.  Lancet Oncol. 2010;  11 934-941
• 21 Mateos M, Richardson P, Schlag R et al. Bortezomib Plus Melphalan-Prednisone Continues to Demonstrate a Survival Benefit Vs Melphalan-Prednisone in the Phase III VISTA Trial in Previously Untreated Multiple Myeloma After 3 Years’ Follow-up and Extensive Subsequent Therapy Use.  ASH Annual Meeting Abstracts. 2009;  Abstract 3859
• 22 Palumbo A, Bringhen S, Rossi D et al. Bortezomib, Melphalan, Prednisone and Thalidomide (VMPT) Followed by Maintenance with Bortezomib and Thalidomide for Initial Treatment of Elderly Multiple Myeloma Patients.  ASH Annual Meeting Abstracts. 2009;  114 (22) 128
• 23 Palumbo A, Gay F. How to treat elderly patients with multiple myeloma: combination of therapy or sequencing.  Hematology. 2009;  2009 (1) 566-577
• 24 Gay F, Palumbo A. Management of disease- and treatment-related complications in patients with multiple myeloma.  Medical Oncology. 2010;  27 (0) 43-52
• 25 Baron R. Therapie neuropathischer Schmerzen. In: Diener H C, Putzki N Leitlinien für die Diagnostik und Therapie in der Neurologie.. 4. überarbeitete Aufl. Stuttgart: Georg Thieme Verlag; 2008: 630-640
• 26 Mateos M, Richardson P G. Peripheral Neuropathy with VMP resolves in the majority of patients and shows a rate plateau. 12th International Myeloma Workshop. 2009
• 27 Bringhen S, Larocca A, Rossi D et al. Efficacy and safety of once weekly bortezomib in multiple myeloma patients.  Blood. 2010;  [Epub ahead of print] DOI: 10.1182 /blood-2010-07-294 983