Both İmatinib and Nilotinib Treatment Associated Grade 3-4 Skin Rash, is it Predictable Before Tyrosine Kinase Inhibitor Treatment? A Case Report

Yıl 2018, Cilt: 40 Sayı: 1, 71 - 74, 31.01.2018

İbrahim Vasi Sevda Keleş Taşdüzen Hava Üsküdar Teke , Eren Gündüz Neslihan Andıç Olga Meltem Akay

https://doi.org/10.20515/otd.347085

Öz

Chronic myeloid leukemia (CML), characterized with The Philadelphia (Ph) chromosome,
is a myeloproliferative disorder. Imatinib mesylate, the first selective
tyrosine kinase inhibitor targeting Bcr-Abl protein. Nilotinib and dasatinib
are second-generation tyrosine kinse inhibitörse, that have been approved for
imatinib resistant CML. Most common side effects of these tyrosine kinase
inibitors are myelosuppresion, nausea, vomiting, diarrhea and grade 1-2 skin
rash. Due to imatinib treatment incidence of grade 3-4 skin rash is 3-5% and nilotinib
treatment incidence grade 3-4 skin rash is <1%. Philadelphia(Ph) chromosome
positive chronic phase CML were diagnosed to 50-year-old female patient with
leukocytosis, and started treatment with imatinib. In the third month of
treatment with imatinib was seen itchy, raised skin lesions and skin biopsy was
performed on the identification. It is evaluated as drug eruption associated
imatinib, so imatinib interrupted and then nilotinib treatment 2*400 mg/day was
started. In the third year of nilotinib treatment hyperemic lesions and itching
was detected and nilotinib treatment dose reduced 2*200 mg/day and local
steroid treatment started. In the eighth year of treatment with nilotinib was
seen grade 3-4 rash (figure1) and treatment was delayed and systemic steroid
treatment was added. Because of development grade 3-4 skin rash, nilotinib
could not resumed and was replaced with dasatinib treatment. Both two tyrosine
kinase inhibitör treatment with in our patients with grade 3-4 skin rash, skin
reactions under dasatinib continues to be closely monitored.

Anahtar Kelimeler

skin rash, tyrosine kinase inhibitor

Hem İmatinib Hem de Nilotinib Tedavisi altında Gelişen Grade 3-4 Cilt Döküntüsü, Tirozin Kinaz İnhibitörü Başlamadan Öngörülebilir mi? Olgu sunumu

Öz

Kronik miyeloid lösemi (KML), Philadelphia (Ph) kromozomu pozitifliği ile
karakterize kronik miyeloproliferatif bir hastalıktır. İmatinib mesylate,
BCR-ABL proteinini hedef alan ilk seçici tirozin kinaz inhibitörüdür (TKI).
Nilotinib ve dasatinib ise imatinib dirençli KML tedavisinde kullanılan 2.kuşak
tirozin kinaz inhibitörleridir. Bu tirozin kinaz inhibitörlerinin en sık
görülen yan etkileri miyelosupresyon, bulantı, kusma, ishal ve grade 1-2 cilt
döküntüleridir. İmatinibe bağlı grade 3-4 cilt döküntüsünün görülme olasılığı
%3-5, nilotinibe bağlı grade 3-4 cilt döküntüsünün görülme olasılığı ise
<%1’dir. Olgumuz 50 yaşındaki kadın hastaya lökositoz nedenli Ph kromozomu
pozitif kronik faz KML tanısı konuldu ve imatinib tedavisi başlandı. İmatinib
tedavisinin 3. ayında kaşıntılı, ciltten kabarık lezyonlar saptanması üzerine
cilt biyopsisi yapıldı ve ilaç erupsiyonu olarak değerlendirilerek imatinib
tedavisi kesildi, nilotinib 2*400 mg/gün başlandı. Nilotinib tedavisinin
3.yılında ciltte hiperemik lezyonlar ve kaşıntı saptanması üzerine nilotinib
tedavisi 2*200 mg/gün dozuna düşürüldü ve lokal tedavi başlandı. Nilotinib
tedavisinin 8.yılında grade 3-4 cilt döküntüsü gelişen hastada tedaviye ara
verildi ve sistemik steroid eklendi. Grade 3-4 döküntü gelişmesi nedeni ile
nilotinib tekrar başlanamadı, ve tedavisi dasatinib ile değiştirildi. TKI ile
grade 3-4 cilt döküntüsü gelişen hastamızda, dasatinib altında da cilt
reaksiyonu gelişip-gelişmeyeceği açısından yakın takip devam etmektedir.

Anahtar Kelimeler

cilt döküntüsü, tirozin kinaz inhibitörü

Kaynakça

• 1.Faderl S, Talpaz M, Estrov Z, et al. 1999. The biology of chronic myeloid leukemia. N Engl J Med, 341:164– 72.
• 2.Kantarjian H, Giles F, Wunderle L, et al. 2006. Nilotinib in imatinib-resistant CML and philadelphia chromosome – positive ALL. N Engl J Med, 354:2542–51.
• 3.Giles, F.J, Abruzzese, E, Rosti, G, et al. 2010. Nilotinib is active in chronic and accelerated phase chronic myeloid leukemia following failure of imatinib and dasatinib therapy. Leukemia 24, 1299–1301.
• 4.Schwab C. 2006. Advances in the management of chronic myeloid leukemia with Abl kinase inhibitors. Oncology Briefings, 4:1–3.
• 5.Package insert. Tasigna (nilotinib). East Hanover, NJ: Novartis Pharmaceuticals; 2010.
• 6.Mauro MJ, Deininger MW. Management of drug toxicities in chronic myeloid leukaemia.Best Pract Res Clin Haematol. 2009;22:409–429.
• 7.Kantarjian HM, Giles F, Hochhaus A, et al. Nilotinib in patients with imatinib-resistant or -intolerant chronic myelogenous leukemia in chronic phase (CML-CP): Updated Phase II results. J Clin Oncol. 2008 126:7010.
• 8.Quintas-Cardama A, Kantarjian H, O’Brien S, et al. Pleural effusion in patients with chronic myelogenous leukemia treated with dasatinib after imatinib failure. J Clin Oncol. 2007;25:3908–3914.
• 9.Bolognia JL MD, Jorizzo JL, Schaffer JV. Drug Reactions. Dermatology. 2012;21,335-356
• 10.Natali P.G, Nicotra M.R, Sures I, et al. 1992. Expression of c-kit receptor in normal and transformed human nonlymphoid tissues. Cancer Res. 52, 6139–6143.
• 11.El-Agamy D.S. 2012. Anti-allergic effects of nilotinib on mast cell mediated anaphylaxis like reactions. Eur J Pharmacol. 2012 Apr 5 ;680(1-3):115-21.
• 12.Kantarjian H.M, Giles F.J, Bhalla K.N, et al. 2011. Nilotinib is effective in patients with chronic myeloid leukemia in chronic phase after imatinib resistance or intolerance: 24-month follow-up results. Blood. 2011 Jan 27;117(4):1141-5.
• 13.Rosti G, Palandri F, Castagnetti F, Breccia M, Levato L, Gugliotta G, Capucci A, Cedrone M, Fava C, Intermesoli T, Cambrin GR, Stagno F, Tiribelli M, Amabile M, Luatti S, Poerio A, Soverini S, Testoni N, Martinelli G, Alimena G, Pane F, Saglio G, Baccarani M; GIMEMA CML Working Party.Nilotinib for the frontline treatment of Ph_ chronic myeloid leukemia. Blood. 2009 Dec 3;114(24):4933-8.
• 14.Nicolini FE, Turkina A, Shen ZX, Gallagher N, Jootar S, Powell BL, De Souza C, Zheng M, Szczudlo T, le Coutre P. Expanding Nilotinib Access in Clinical Trials (ENACT): an open-label, multicenter study of oral nilotinib in adult patients with imatinib-resistant or imatinib-intolerant Philadelphia chromosome-positive chronic myeloid leukemia in the chronic phase. Cancer. 2012 Jan 1;118(1):118-26.
• 15.Guilhot F.2004. Indications for imatinib mesylate therapy and clinical management. Oncologist, 9:271-81.