Medical Policy Title: HDC & Autologous ARBenefits Approval: 02/08/2012

Transcription

1 Medical Plicy Title: HDC & Autlgus ARBenefits Apprval: 02/08/2012 Stem&/r Prgenitr Cell Supprt, Germ Cell Tumrs Effective Date: 01/01/2013 Dcument: ARB0416:01 Revisin Date: 10/24/2012 Cde(s): 38230, Bne marrw harvesting fr transplantatin 38240, Bne marrw r bld-derived peripheral stem cell transplantatin; allgenic 38241, Bne marrw r bld-derived peripheral stem cell transplantatin; autlgus 38242, Bne marrw r bld-derived peripheral stem cell transplantatin; allgeneic dnr lymphcyte infusins Public Statement: Administered by: Autlgus stem cell transplant is cvered fr thse patients wh meet criteria, with authrizatin thrugh case management by American Health Hlding at (ptin 2). Medical Plicy Statement: High dse chemtherapy with autlgus bne marrw, stem cell, r prgenitr cell supprt fr the treatment f germ cell tumr f the testicle, vary, mediastinum r retrperitneum is cnsidered medically necessary and is cvered: Fr incmplete remissin fllwing standard chemtherapy: Fr cnslidatin fllwing secnd cmplete remissin induced by standard chemtherapy; Fllwing secnd relapse t standard chemtherapy. Limits: High dse chemtherapy with allgeneic stem and/r prgenitr cell supprt is nt cvered fllwing autlgus stem and/r prgenitr cell transplantatin. Page 1 f 5

2 Tandem high dse chemtherapy with autlgus stem and/r prgenitr cell supprt is nt cvered fr any diseases ther than multiple myelma and Waldenstrm s macrglbulinemia. A secnd r subsequent curse f high dse chemtherapy with allgeneic r autlgus stem cell and/r prgenitr cell supprt fr treatment f relapsed disease is cvered nly fr patients wh have shwn a cmplete respnse t the initial high dse chemtherapy/transplant regimen. Cverage f high dse chemtherapy with allgeneic r autlgus stem and/r prgenitr cell supprt fr a patient with tw active malignant diseases is cvered nly if bth diseases have a specific cverage plicy and the patient meets all criteria fr bth high dse chemtherapy with stem and/r prgenitr cell treatment regimens. Backgrund: Germ cell tumrs cmprise the vast majrity f primary testicular neplasms, althugh germ cell tumrs can arise in the vary and in extragnadal lcatins, such as in the retrperitneum r mediastinum. Germ cell tumrs can be classified accrding t their histlgy, stage, prgnsis, r respnse t chemtherapy. Histlgies include seminma, embrynal carcinma, teratma, chricarcinma, ylk DAC tumr, and mixed germ cell tumrs. Seminmas are the mst cmmn; all ther types f germ cell tumrs may be cllectively referred t as nn-seminmatus germ cell tumrs. The stage is dependent f the lcatin f the tumr. In terms f testicular tumr, Stage I is limited t the testis, Stage II is disease spread t the retrperitneum, and Stage III disease is distant (supradiaphragmatic) disease. Prgnstic classificatins systems take int accunt the site f the primary tumr (testis versus extragnadal), tumr marker levels, and site f visceral disease. Therapy is ften dictated by the prgnsis. Fr example, first line therapy fr gd and intermediate risk patients is usually 3 r 4 cycles f the cmbinatin regimen f cisplatin, blemycin and etpside. Secnd line therapy ften cnsists f cmbined therapy with vinblastine, ifsfamide, and cisplatin. Patients whse tumrs are resistant t cisplatin may prceed t regimens cntaining carbplatin. Chemtherapy is ften fllwed by surgery t remve residual masses. Regimens used fr relapsed disease include cisplatin plus ifsfamide, cmbined either with etpside r vinblastine. The prbability f lng-term cntinuus cmplete respnse diminishes with each successive relapse. The term partial respnse is defined as at least a 50% reductin in tumr burden. Page 2 f 5

3 The term refractry is defined as a less than 50% reductin in tumr burden. Therefre, even thse tumrs that exhibited a 50% reductin in tumr burden, fr example, wuld be cnsidered refractry. Tumr respnse can be measured using serial CT scans, r levels f circulating tumr markers, such as alpha fetprtein. Randmized cntrlled trials have failed shw any benefit f high dse chemtherapy autlgus stem cell supprt versus standard platinum based chemtherapy fr initial treatment f metastatic germ cell tumr. Single cycle high dse chemtherapy autlgus stem cell supprt versus standard salvage chemtherapy als failed t shw any benefit as salvage therapy fr patients failing first-line platinum chemtherapy fr advanced germ cell tumrs. Despite the findings in the latter study, a large retrspective case series f patients wh failed first line therapy did demnstrate significant imprved survival fllwing 2-cycle high dse chemtherapy - stem cell supprt. Agarwal and clleagues reprted their experience at Stanfrd in treating 37 cnsecutive patients wh received high-dse chemtherapy and autlgus HSCT between 1995 and 2005 fr relapsed germ-cell tumrs (Agarwal, 2009). The median patient age was 28 years, with 34 males and 3 females. Primary tumr sites included 24 testes/adnexal, 10 chest/neck/retrperitneal, and 3 central nervus system. Twenty-nine f the patients had received prir standard salvage chemtherapy. Three year verall survival was 57% and 3 year prgressin-free survival was 49%. In 2005, Pic and clleagues reprted n a randmized trial cmparing 4 cycles f cnventinal-dse chemtherapy t 3 cycles f the same regimen fllwed by carbplatin-based high-dse chemtherapy plus autlgus HSCT in 280 patients wh had relapsed after a cmplete r partial remissin fllwing first-line therapy with a cisplatin-based regimen (Pic, 2005). Hwever, high-dse chemtherapy in the experimental arm fllwed 3 cycles f cnventinal-dse chemtherapy, which differs frm mst current practice in the U.S., where a single cycle is used prir t high-dse chemtherapy. As a cnsequence, 38 f 135 (28%) randmized t the high-dse chemtherapy arm did nt receive high-dse chemtherapy because f prgressin, txicity, r withdrawal f cnsent. Natinal Cmprehensive Cancer Netwrk (NCCN) Guidelines The 2010 (v ) NCCN guidelines fr the treatment f testicular cancer state that if a patient with favrable prgnstic factrs (defined as testicular primary site, prir cmplete respnse t first line therapy, lw levels f serum markers and lw vlume disease), experiences an incmplete respnse t cnventinal-dse salvage chemtherapy therapy r relapses after salvage chemtherapy, high-dse chemtherapy with autlgus stem cell supprt is the preferred ptin. Patients with unfavrable prgnstic factrs fr cnventinal-dse salvage therapy (e.g. an incmplete respnse t first line therapy) and patients requiring third-line salvage therapy are cnsidered fr treatment with high-dse chemtherapy plus autlgus stem cell supprt (categry 2B). The guidelines d nt address the use f tandem r sequential HSCT in the treatment f testicular tumrs. Page 3 f 5

4 References: Agarwal R, Dvrak CC, Stckerl-Gldstein KE et al.(2009) High-dse chemtherapy fllwed by stem cell rescue fr high-risk germ cell tumrs: the Standard experience. Bne Marrw Transplant 2009; 43(7): Beyer J, Kingreen D, Krause M, et al.(1997) Lng-term survival f patients with recurrent r refractry germ cell tumrs after high dse chemtherapy. Cancer 1997; 79: Bkemeyer C, Harstrick A, Beyer J, et al.(1998) The use f dse-intensified chemtherapy in the treatment f metastatic nnseminmatus testicular germ cell tumrs. German Testicular Cancer Study Grup. Semin Oncl 1998; 25(2 sup 4):24-32; discussin Drz JP, Kramar A, Birn P et al.(2007) Failure f high-dse cyclphsphamide and etpside cmbined with duble-dse cisplatin and bne marrw supprt in patients with high-vlume metastatic nnseminmatus germ-cell tumurs: mature results f a randmized trial. Eur Url 2007; 51(3): Einhrn LH, Williams SD, Chamness A, et al.(2007) High-dse chemtherapy and stem-cell rescue fr metastatic germ-cell tumrs. New Engl J Med, 2007; 357: Germ-cell tumrs. Letters t the editr. N Engl J Med 2007; 357(17): Gdwin A, Gurney H, Gttlieb D.(2007) Allgeneic bne marrw transplant fr refractry mediastinal germ cell tumur: pssible evidence f graft-versus-tumur effect. Intern Med J 2007; 37(2): High-dse chemtherapy plus allgeneic stem cells t treat chrnic lymphcytic leukemia r small lymphcytic lymphma Blue Crss Blue Shield Assciatin Technlgy Evaluatin Center Assessment. Internatinal Germ Cell Cancer Cllabrative Grup.(1997). Internatinal Germ Cell Cnsensus Classificatin: a prgnstic factr-based staging system fr metastatic germ cell cancers. J Clin Oncl 1997; 15(2): Kllmannsberger C, Hartmann JT, Kanz L, et al.(1999) Therapy-related malignancies fllwing treatment f germ-cell cancer. Int J Cancer 1999; 83: Lazarus HM, Stiff PJ, Carreras J et al.(2007) Utility f single versus tandem auttransplants fr advanced testes/germ cell cancer: a Center fr Internatinal Bld and Marrw Transplant Research (CIBMTR) analysis. Bil Bld Marrw Transplant Page 4 f 5

5 2007; 13(7): Lrch A, Kllmannsberger C, Hartmann JT et al.(2007) Single versus sequential highdse chemtherapy in patients with relapsed r refractry germ-cell tumrs: a prspective randmized multicenter trial f the German Testicular Cancer Study Grup. J Clin Oncl 2007; 25(19): Ltz JP, Bui B, Gmez F et al(2005) Sequential high-dse chemtherapy prtcl fr relapsed pr prgnsis germ cell tumrs cmbining tw mbilizatin and cytreductive treatments fllwed by three high-dse chemtherapy regimens supprted by autlgus stem cell transplantatin. Ann Oncl 2005; 16(3): Mandanas RA, Saez RA, Epstein RB, et al.(1998) Lng-term results f autlgus marrw transplantatin fr relapsed r refractry male r female germ cell tumrs. BMT 1998; 21: Mtzer RJ, Nichls CJ, Marglin KA, et al.(2007) Phase III randmized trial f cnventinal-dse chemtherapy with r withut high-dse chemtherapy and autlgus hematpietic stem-cell rescue as first-line treatment fr patients with prprgnsis metastatic germ cell tumrs. J Clin Oncl, 2007; 25: Natinal Cmprehensive Cancer Netwrk. Testicular cancer. Clinical Practice Guidelines in Onclgy. Natinal Cmprehensive Cancer Netwrk. V Available at: Accessed March Pic JL, Rsti G, Kramer A, et al.(2005) A randmized trial f high-dse chemtherapy in the salvage treatment f patients mailing first-line platinum chemtherapy fr advanced germ cell tumrs. Ann Onclgy, 2005; 16: Siegert W, Beyer J.(1998) Germ cell tumrs: dse intensive therapy. Semin Oncl 1998; 25: Sbecks RM, Vgelzang NJ.(1999) High-dse chemtherapy with autlgus stem-cell supprt fr germ cell tumrs: a critical review. Semin Oncl 1999; 26: Applicatin t Prducts This plicy applies t ARBenefits. Cnsult ARBenefits Summary Plan Descriptin (SPD) fr additinal infrmatin. Last mdified by: SCS Date: 10/25/2012 Page 5 f 5