Subject: Venetoclax (Venclexta ) Tablet

Transcription

1 09-J Original Effective Date: 09/15/16 Reviewed: 07/11/18 Revised: 01/15/19 Subject: Venetclax (Venclexta ) Tablet THIS MEDICAL COVERAGE GUIDELINE IS NOT AN AUTHORIZATION, CERTIFICATION, EXPLANATION OF BENEFITS, OR A GUARANTEE OF PAYMENT, NOR DOES IT SUBSTITUTE FOR OR CONSTITUTE MEDICAL ADVICE. ALL MEDICAL DECISIONS ARE SOLELY THE RESPONSIBILITY OF THE PATIENT AND PHYSICIAN. BENEFITS ARE DETERMINED BY THE GROUP CONTRACT, MEMBER BENEFIT BOOKLET, AND/OR INDIVIDUAL SUBSCRIBER CERTIFICATE IN EFFECT AT THE TIME SERVICES WERE RENDERED. THIS MEDICAL COVERAGE GUIDELINE APPLIES TO ALL LINES OF BUSINESS UNLESS OTHERWISE NOTED IN THE PROGRAM EXCEPTIONS SECTION. Dsage/ Administratin Psitin Statement Billing/Cding Reimbursement Prgram Exceptins Definitins Related Guidelines Other References Updates DESCRIPTION: Venetclax (Venclexta) is a selective inhibitr f B-cell lymphma-2 (BCL-2) prtein, an anti-appttic prtein. The verexpressin f BCL-2 in chrnic lymphcytic leukemia (CLL) tumr cells enhances cell survival and is assciated with resistance t chemtherapy. Venetclax was apprved by the FDA in April 2016 fr the treatment f patients with chrnic lymphcytic leukemia (CLL) with 17p deletin, as detected by an FDA apprved test, wh have received at least ne prir therapy. The indicatin was apprved under accelerated apprval based n verall respnse rate (ORR), with cntinued apprval cntingent upn verificatin f clinical benefit in a cnfirmatry trial. In June 2018, cnfirmatry data was submitted t the FDA and venetclax was granted full apprval. In additin, based n the results f the MURANO phase 3 randmized cntrlled trial, the FDA-apprved indicatin was expanded t be the treatment f patients with chrnic lymphcytic leukemia (CLL) r small lymphcytic lymphma (SLL), with r withut 17p deletin, wh have received at least ne prir therapy. Venetclax was previusly granted rphan drug designatin by the FDA fr the treatment f CLL in September In Nvember 2018, the FDA apprved the new indicatin f In cmbinatin with azacitidine r decitabine r lw-dse cytarabine fr the treatment f newly-diagnsed acute myelid leukemia (AML) in adults wh are age 75 years r lder, r wh have cmrbidities that preclude use f intensive inductin chemtherapy. Venetclax was previusly granted rphan drug designatin fr the treatment f AML in February Venetclax, as spnsred by the innvatr drug cmpany, als has rphan drug designatins fr the treatment f multiple myelma (August 2016) and mantle cell lymphma (August 2017). Chrnic lymphcytic leukemia/small lymphcytic lymphma (CLL/SLL) is a mature B-cell lymphma that cmprises apprximately 7% f newly diagnsed cases f Nn-Hdgkin s Lymphma (NHL). CLL and SLL are different manifestatin f the same disease and are managed in much the same way. The main difference is that in CLL the abnrmal lymphcytes are fund in bne marrw and bld, while in SLL

2 they are predminately fund in the lymph ndes and bne marrw. The diagnsis f CLL requires the presence f at least 5,000 clnal B-cells/mcL in the peripheral bld as determined by flw cytmetry quantificatin. Cytgenic abnrmalities that can be detected by flurescence in situ hybridizatin (FISH) testing are present in ver 80% f previusly untreated CLL patients. The 17p chrmsme deletin, del(17p) mutatin, which reflects the lss f the TP53 gene, is assciated with the wrst utcmes and pr respnse t chemtherapy. Abut 7% f newly diagnsed patients have a del(17p) mutatin. The treatment ptins fr CLL have changed drastically in the last several decades. The intrductin f mnclnal antibdies targeting cell surface antigens (e.g., CD20, CD52), immunmdulating agents, and, mst recently, nvel small mlecules inhibiting tyrsine kinases and ther prteins, have led t new and mre effective regimens. Recmmended treatments are based n newly diagnsed vs. refractry disease, and the patient s mutatin status, age, and ther cmrbidities. The safety and efficacy f venetclax leading t initial FDA apprval was established in an pen-label, single-arm, multicenter clinical trial f 106 patients with CLL with del(17p) wh had received at least ne prir therapy. The primary endpint was verall respnse rate (ORR). The median time n treatment at the time f evaluatin was 12.1 mnths (range: 0 t 21.5 mnths). An ORR was bserved in 80.2% (95% CI 71.3 t 87.3%, n=85) f patients, with the majrity achieving partial remissin (69.8%, n=74). Other respnses were as fllws: CR 5.7% (n=6), CRi 1.9% (n=2), and npr 2.38% (n=3). Cnfirmatin f clinical benefit was determined in the randmized MURANO trial f adults with CLL wh had received at least ne line f prir therapy. The cmbinatin f venetclax and rituximab cmpared with bendamustine and rituximab significantly imprved PFS (nt reached vs 17 mnths) and 2-year PFS rate (84.9% vs. 36.3%). The ORR was significantly imprved in the venetclax arm (92.3% vs 72.3%), but the rate f CR plus CRi (8.2% vs 3.6%) was nt. Adverse events were as expected with the fllwing Grade 3 r 4 adverse events in the venetclax and bendamustine arms, respectively; neutrpenia (57.7% vs 38.8%), febrile neutrpenia (3.6% vs 9.6), tumr lysis syndrme (3.1% vs 1.5%), and infusin-related reactin (1.5% vs 5.3%). The Natinal Cmprehensive Cancer Netwrk (NCCN) Guidelines fr CLL/SLL (Versin ) list venetclax in cmbinatin with rituximab (Rituxan) under Preferred regimens fr patients with relapsed r refractry disease with r withut del(17p) mutatin (categry 1 recmmendatins). Fr patients withut a del(17p) mutatin, venetclax mntherapy is listed under Other recmmended regimens as a categry 2A recmmendatin. Fr patients with a del(17p) mutatin, venetclax mntherapy is listed under Preferred regimens as a categry 2A recmmendatin. The NCCN als includes recmmendatins fr tumr lysis syndrme (TLS) prphylaxis and mnitring based n tumr burden when initiating venetclax treatment. The NCCN Guidelines fr B-cell Lymphmas (Versin ) list venetclax mntherapy under Preferred regimen as a categry 2A ptin fr the secnd-line treatment f mantle cell lymphma when there is a shrt respnse duratin t prir chemimmuntherapy (shrter expected median PFS). Venetclax mntherapy is a categry 2A ptin under Other recmmended regimens fr the secnd-line treatment f mantle cell lymphma when there is an extended respnse duratin t prir chemimmuntherapy (lnger expended median PFS). The NCCN Guidelines fr AML (Versin ) list venetclax regimens as categry 2A recmmendatins fr patients 60 years f age r lder in the fllwing scenaris: (1) in cmbinatin with decitabine r azacitidine fr treatment inductin in candidates fr intensive remissin inductin therapy with unfavrable cytgenetic/mlecular markers, antecedent hematlgic disrder, r therapy-related AML; (2) in cmbinatin with decitabine, azacitidine, r lw-dse cytarabine fr treatment inductin when nt a candidate fr intensive remissin inductin therapy r declines intensive therapy, and (3) in cmbinatin with decitabine, azacitidine, r lw-dse cytarabine fr pst-remissin therapy fllwing respnse t previus lwer intensity therapy with the same regimen.

3 POSITION STATEMENT: Cmparative Effectiveness The Fd and Drug Administratin has deemed the drug(s) r bilgical prduct(s) in this cverage plicy t be apprpriate fr self-administratin r administratin by a caregiver (i.e., nt a healthcare prfessinal). Therefre, cverage (i.e., administratin) in a prvider-administered setting such as an utpatient hspital, ambulatry surgical suite, physician ffice, r emergency facility is nt cnsidered medically necessary. Initiatin f venetclax (Venclexta) meets the definitin f medical necessity fr members meeting BOTH f the fllwing criteria ( 1 and 2 ): 1. Venetclax is administered fr an indicatin listed in Table 1, and ALL f the indicatin-specific and maximum-allwable dse criteria are met 2. The member s tumr burden [i.e., abslute lymphcyte cunt (ALC) and lymph nde sizes via CT scan] and ther risk factrs fr tumr lysis syndrme (TLS) have been assessed, and the member will receive apprpriate prphylaxis as necessary Table 1 Indicatins and Specific Criteria Indicatin Specific Criteria Maximum Allwable Dse

4 Acute myelid leukemia (AML) Chrnic lymphcytic leukemia (CLL)/ small lymphcytic lymphma (SLL) Mantle cell lymphma (MCL) EITHER f the fllwing ( 1 r 2 ): 1. BOTH f the fllwing ( a and b ): a. Member is 60 years f age r lder b. ANY f the fllwing ( i, ii, r iii ): i. Venetclax is being used in cmbinatin with decitabine r azacitidine fr treatment inductin in candidates fr intensive remissin inductin therapy with unfavrable cytgenetic/mlecular markers, antecedent hematlgic disrder, r therapy-related AML ii. iii. Venetclax is being used in cmbinatin with decitabine, azacitidine, r lw-dse cytarabine fr treatment inductin when NOT a candidate fr intensive remissin inductin therapy r declines intensive therapy Venetclax is being used in cmbinatin with decitabine, azacitidine, r lw-dse cytarabine fr pst-remissin therapy fllwing respnse t previus lwer intensity therapy with the same regimen 2. BOTH f the fllwing ( a and b ): a. The member has relapsed r refractry disease b. The member has received prir treatment fr their AML with TWO r mre different lines f therapy* ALL f the fllwing ( 1, 2, and 3 ): 1. The member has relapsed r refractry disease 2. The member has received at least ne prir therapy fr treatment f their disease 3. Venetclax will be used as either single-agent treatment r in cmbinatin with rituximab BOTH f the fllwing ( 1 and 2 ): 1. EITHER f the fllwing ( a r b ): a. Venetclax is being used as secnd-line r later therapy fr relapsed r refractry disease b. Member had a partial respnse t inductin therapy and venetclax is being used t achieve a cmplete respnse 2. Venetclax will be used as single-agent treatment Fr pst-remissin therapy r inductin therapy in members 60 years f age r lder: 400 mg daily (if used in cmbinatin with azacitidine r decitabine) 600 mg daily (if used in cmbinatin with lw-dse cytarabine) Fr relapsed r refractry disease: 400 mg daily Dse must be achieved using the fewest number f tablets pssible 400 mg rally nce daily achieved using the fewest number f tablets pssible 400 mg rally nce daily achieved using the fewest number f tablets pssible

5 Multiple myelma (MM) [rphan indicatin] ALL f the fllwing ( 1, 2, 3, and 4 ): 1. The member has relapsed r refractry disease 2. The member has been previusly treated fr MM with at least THREE separate lines f therapy 3. Venetclax will be use in ANY f the fllwing treatment regimens ( a, b, r c ): a. As mntherapy b. In cmbinatin with dexamethasne c. In cmbinatin with bth brtezmib and dexamethasne 4. The member s baseline (i.e., within 90 days prir t initiating treatment with venetclax) serum mnclnal prtein (M-prtein) level, as detected by serum prtein electrphresis (SPEP), is prvided # 800 mg rally nce daily achieved using the fewest number f tablets pssible Duratin f apprval: 6 mnths *Investigatinal drug treatment as part f a registered clinical trial qualifies as an eligible line f therapy. The Natinal Cmprehensive Cancer Netwrk (NCCN) Guidelines fr AML, list enrllment in a clinical trial as the strngly preferred ptin fr patients with relapsed/refractry AML. # If the M-prtein is undetectable by SPEP, baseline serum free light chain (SFLC) levels (kappa and lambda, as detected by serum free light chain assay (SFLCA), must als be prvided Cntinuatin f venetclax meets the definitin f medical necessity fr members meeting ALL f the fllwing criteria ( 1 t 4 ): 1. Authrizatin r reauthrizatin fr venetclax has been previusly apprved by Flrida Blue r anther health plan in the past 2 years fr the treatment f a cnditin listed in Table 1, OR the member previusly met ALL indicatin-specific initiatin criteria. 2. The member has nt had disease prgressin during treatment with venetclax 3. ONE f the fllwing based n the disease being treated: a. Fr AML Fr released r refractry AML - venetclax will be used as a single agent r in a cmbinatin regimen Fr pst-remissin therapy r inductin therapy in members 60 years f age r lder - venetclax will be used in cmbinatin with decitabine, azacitidine, r lw-dse cytarabine b. Fr CLL/SLL venetclax will be used as either a single agent r in cmbinatin with rituximab c. Fr MCL - venetclax will be used as a single agent

6 d. Fr MM venetclax will be used as a single-agent, in cmbinatin with dexamethasne, r in cmbinatin with bth dexamethasne and brtezmib 4. The dsage des nt exceed the fllwing based n the indicatin fr use - the dse must be achieved using the fewest number f tablets pssible: AML Fr released r refractry disease 400 mg daily Fr pst-remissin therapy r inductin therapy in members 60 years f age r lder 400 mg daily (if used in cmbinatin with azacitidine r decitabine) 600 mg daily (if used in cmbinatin with lw-dse cytarabine) CLL/SLL 400 mg daily. If using fr CLL/SLL in cmbinatin with rituximab, venetclax will nt be used fr lnger than 24 mnths frm cycle 1 day 1 f rituximab initiatin. MCL 400 mg daily MM 800 mg daily Duratin f apprval: 1 year DOSAGE/ADMINISTRATION: THIS INFORMATION IS PROVIDED FOR INFORMATIONAL PURPOSES ONLY AND SHOULD NOT BE USED AS A SOURCE FOR MAKING PRESCRIBING OR OTHER MEDICAL DETERMINATIONS. PROVIDERS SHOULD REFER TO THE MANUFACTURER S FULL PRESCRIBING INFORMATION FOR DOSAGE GUIDELINES AND OTHER INFORMATION RELATED TO THIS MEDICATION BEFORE MAKING ANY CLINICAL DECISIONS REGARDING ITS USAGE. FDA-apprved The treatment f adult patients with chrnic lymphcytic leukemia (CLL) r small lymphcytic lymphma (SLL), with r withut17p deletin, wh have received at least ne prir therapy. Initiate therapy at 20 mg nce daily fr 7 days, fllwed by a weekly ramp-up dsing schedule t the recmmended daily dse f 400 mg. If being used in cmbinatin with rituximab, rituximab is started after the patient has cmpleted the 5-week dse ramp-up and has received the 400 mg venetclax dse fr 7 days. Rituximab is given n day 1 f each 28-day cycle fr 6 cycles at a dse f 375 mg/m2 IV fr cycle 1 and then 500 mg/m2 IV fr cycles 2 t 6. Patients cntinue venetclax nce daily fr 24 mnths ttal frm cycle 1 day 1 f rituximab. If given as mntherapy, the prduct labeling recmmends that venetclax be taken until disease prgressin r unacceptable txicity is bserved. Tablets shuld be taken rally nce daily with a meal and water. D nt chew, crush, r break tablets. Week 1 20 mg Week 2 50 mg Week mg Week mg Week 5 and beynd 400 mg

7 Treatment can cause rapid reductin in tumr and thus pses a risk fr tumr lysis syndrme (TLS) in the initial 5-week ramp-up phase. Perfrm prphylaxis fr TLS and mnitring as recmmend in the prduct labeling. In cmbinatin with azacitidine, r decitabine, r lw-dse cytarabine fr the treatment f newlydiagnsed acute myelid leukemia (AML) in adults wh are age 75 years r lder, r wh have cmrbidities that preclude use f intensive inductin chemtherapy. This indicatin is apprved under accelerated apprval based n respnse rates, and cntinued apprval fr this indicatin may be cntingent upn verificatin and descriptin f clinical benefit in cnfirmatry trials. Initiate therapy at 100 mg n Day 1, 200 mg n Day 2, 400 mg n Day 3, and then, fr Days 4 and beynd, 400 mg nce daily (when dsing in cmbinatin with azacitidine r decitabine) r 600 mg nce daily (when dsing in cmbinatin with lw-dse cytarabine). The prduct labeling recmmends that venetclax, in cmbinatin with azacitidine r decitabine r lw-dse cytarabine, be taken until disease prgressin r unacceptable txicity is bserved. Patients treated with venetclax may develp TLS. All AML patients shuld have a white bld cell cunt less than /L prir t initiatin f venetclax. Cytreductin prir t treatment may be required. Perfrm prphylaxis fr TLS and mnitring as recmmend in the prduct labeling. Dse Adjustments Interrupt dsing r reduce dse f venetclax fr txicities. The specific recmmendatins depend n the indicatin fr use, the type and severity f the adverse event, and number f ccurrences. Refer t the prduct labeling fr specific recmmendatins. Dsage mdificatins r avidance f venetclax are recmmended fr cncmitant use with strng r mderate CYP3A inhibitrs r P-gp inhibitrs. The specific recmmendatins depend n the indicatin fr use and the interacting drug. Refer t the prduct labeling fr specific recmmendatins. Hepatic Impairment N dse adjustment is recmmended in patients with mild r mderate hepatic impairment A recmmended dse has nt been determined fr patients with severe hepatic impairment. Renal Impairment: Patients with reduced renal functin (CrCl <80 ml/min) are at increased risk f TLS. These patients may require mre intensive prphylaxis and mnitring. N dse adjustment is needed fr patients with mild r mderate renal impairment (CrCl 30 ml/min) A recmmended dse has nt been determined fr patients with severe renal impairment (CrCl <30 ml/min) r patients n dialysis. Drug Availability 10 mg, 50 mg, and 100 mg film-cated tablets as described belw: Packaging Presentatin Number f Tablets Natinal Drug Cde (NDC)

8 CLL/SLL Starting Pack Each pack cntains fur weekly wallet blister packs: Week 1 (14 x 10 mg tablets) Week 2 (7 x 50 mg tablets) Week 3 (7 x 100 mg tablets) Week 4 (14 x 100 mg tablets) mg Wallet 14 x 10 mg tablets mg Wallet 7 x 50 mg tablets mg Unit Dse 2 x 10 mg tablets mg Unit Dse 1 x 50 mg tablet mg Unit Dse 1 x 100 mg tablet mg Bttle 120 x 100 mg tablets x 100 mg tablets PRECAUTIONS: Bxed Warning Nne Cntraindicatins Cncmitant use f venetclax with strng inhibitrs f CYP3A at initiatin and during ramp-up phase in patients with CLL/SLL due t the ptential fr increased risk f tumr lysis syndrme Precautins/Warnings Tumr Lysis Syndrme (TLS): TLS, including fatal events and renal failure requiring dialysis, has ccurred in previusly treated CLL patients with high tumr burden when treated with venetclax. Anticipate TLS; assess risk in all patients. Premedicate with anti-hyperuricemics and ensure adequate hydratin. Emply mre intensive measures (intravenus hydratin, frequent mnitring, hspitalizatin) as verall risk increases. See the prduct labeling fr specific recmmendatins. Neutrpenia: In patients with CLL, Grade 3 r 4 neutrpenia develped in 64% f patients and Grade 4 neutrpenia develped in 31% f patients treated with venetclax in cmbinatin with rituximab. Grade 3 r 4 neutrpenia develped in 63% f patients and Grade 4 neutrpenia develped in 33% f patients treated with venetclax mntherapy. Febrile neutrpenia ccurred in 4% f patients treated with venetclax in cmbinatin with rituximab and in 6% f patients treated with venetclax mntherapy. Baseline neutrphil cunts wrsened in 97% t 100% f patients

9 treated with venetclax in cmbinatin with azacitidine r decitabine r lw-dse cytarabine. Neutrpenia can recur with subsequent cycles f therapy. Mnitr bld cunts and fr signs f infectin; manage as medically apprpriate. Immunizatin: D nt administer live attenuated vaccines prir t, during, r after venetclax treatment. Embry-Fetal Txicity: May cause embry-fetal harm. Advise females f reprductive ptential f the ptential risk t a fetus and t use effective cntraceptin during treatment. Lactatin: Discntinue breastfeeding. Drug Interactins: If pssible, avid cncmitant use f venetclax with mderate CYP3A inhibitrs, strng r mderate CYP3A inducers, P-gp inhibitrs, r narrw therapeutic index P-gp substrates. Adverse Reactins: The mst cmmn adverse reactins ( 20%) were neutrpenia, diarrhea, nausea, anemia, upper respiratry tract infectin, thrmbcytpenia, and fatigue. BILLING/CODING INFORMATION: The fllwing cdes may be used t describe: HCPCS Cding C9399 Unclassified drugs r bilgicals (Hspital Outpatient Use ONLY) J8999 Prescriptin drug, ral, chemtherapeutic, Nt Otherwise Specified ICD-10 Diagnsis Cdes That Supprt Medical Necessity C C83.09 Small cell B-cell lymphma C C83.19 Mantle cell lymphma C90.00 Multiple myelma nt having achieved remissin C90.02 Multiple myelma in relapse C90.10 Plasma cell leukemia nt having achieved remissin C90.12 Plasma cell leukemia in relapse C90.20 Extramedullary plasmacytma nt having achieved remissin C90.22 Extramedullary plasmacytma in relapse C90.30 Slitary plasmacytma nt having achieved remissin

10 C90.32 Slitary plasmacytma in relapse C91.10 Chrnic lymphcytic leukemia f B-cell type nt having achieved remissin C91.12 Chrnic lymphcytic leukemia f B-cell type in relapse C92.00 Acute myelblastic leukemia, nt having achieved remissin C92.01 Acute myelblastic leukemia, in remissin C92.02 Acute myelblastic leukemia, in relapse C92.50 Acute myelmncytic leukemia, nt having achieved remissin C92.51 Acute myelmncytic leukemia, in remissin C92.52 Acute myelmncytic leukemia, in relapse C92.60 Acute myelid leukemia with 11q23-abnrmality, nt having achieved remissin C92.61 Acute myelid leukemia with 11q23-abnrmality, in remissin C92.62 Acute myelid leukemia with 11q23-abnrmality, in relapse C92.A0 Acute myelid leukemia with multilineage dysplasia, nt having achieved remissin C92.A1 Acute myelid leukemia with multilineage dysplasia, in remissin C92.A2 Acute myelid leukemia with multilineage dysplasia, in relapse REIMBURSEMENT INFORMATION: Refer t sectin entitled POSITION STATEMENT. PROGRAM EXCEPTIONS: Federal Emplyee Prgram (FEP): Fllw FEP guidelines. State Accunt Organizatin (SAO): Fllw SAO guidelines. Medicare Part D: BCBSF has delegated t Prime Therapeutics authrity t make cverage determinatins fr the Medicare Part D services referenced in this guideline.

11 Medicare Advantage: N Natinal Cverage Determinatin (NCD) and/r Lcal Cverage Determinatin (LCD) were fund at the time f guideline creatin. DEFINITIONS: Nne RELATED GUIDELINES: Allgeneic Bne Marrw and Stem Cell Transplantatin, Autlgus Bne Marrw and Stem Cell Transplantatin, Bendamustine HCl (Bendeka, Treanda ) Injectin Ibrutinib (Imbruvica), 09-J Idelalisib (Zydelig) Oral Tablet, 09-J Immune Glbulin Therapy, 09-J Obinutuzumab (Gazyva) Injectin, 09-J Rasburicase (Elitek), 09-J Rituximab (Rituxan), 09-J OTHER: Nne REFERENCES: 1. Aldss I, Yang D, Aribi A, et al. Efficacy f the cmbinatin f venetclax and hypmethylating agents in relapsed/refractry acute myelid leukemia. Haematlgica Mar Besbes S, Pcard M, Mirshahi M, et al. The first MCL-1-selective BH3 mimetics have therapeutic ptential fr chrnic lymphcytic leukemia. Crit Rev Oncl Hematl 2016;100: Clinical Pharmaclgy [Internet]. Tampa (FL): Gld Standard, Inc.; 2018 [cited 2018 Jun 18]. Available frm: 4. Cutre S, Chi M, Furman RR, et al: Venetclax fr patients with chrnic lymphcytic leukemia wh prgressed during r after idelalisib therapy. Bld 2018; 131(15): Davids MS, Hallek M, Wierda W, et al. Cmprehensive Safety Analysis f Venetclax Mntherapy fr Patients with Relapsed/Refractry Chrnic Lymphcytic Leukemia. Clin Cancer Res Jun 12. pii: clincanres DiNard CD, Rausch CR, Bentn C, et al. Clinical experience with the BCL2-inhibitr venetclax in cmbinatin therapy fr relapsed and refractry acute myelid leukemia and related myelid malignancies. Am J Hematl Mar;93(3): DRUGDEX System [Internet]. Greenwd Village (CO): Thmsn Micrmedex; Updated peridically [cited 2018 Jun 18]. Available frm:

12 8. Freise KJ, Jnes AK, Verdug ME, et al. Mving Beynd Maximum Tlerated Dse fr Targeted Onclgy Drugs: Use f Clinical Utility Index t Optimize Venetclax Dsage in Multiple Myelma Patients. Clin Pharmacl Ther Dec;102(6): Hallek M, Chesn BD, Catvsky D, et al. Guidelines fr the diagnsis and treatment f chrnic lymphcytic leukemia: a reprt frm the Internatinal Wrkshp n Chrnic Lymphcytic Leukemia updating the Natinal Cancer Institute-Wrking Grup 1996 guidelines. Bld Jun 15;111(12): Jnes JA, Mat AR, Wierda WG, et al: Venetclax fr chrnic lymphcytic leukaemia prgressing after ibrutinib: an interim analysis f a multicentre, pen-label, phase 2 trial. Lancet Oncl 2018; 19(1): Knpleva M, Pllyea DA, Ptluri J, et al. Efficacy and Bilgical Crrelates f Respnse in a Phase II Study f Venetclax Mntherapy in Patients with Acute Myelgenus Leukemia.b Cancer Discv Oct;6(10): Kumar S, Kaufman JL, Gasparett C, et al. Efficacy f venetclax as targeted therapy fr relapsed/refractry t(11;14) multiple myelma. Bld Nv 30;130(22): Mreau P, Chanan-Khan A, Rberts AW, et al. Prmising efficacy and acceptable safety f venetclax plus brtezmib and dexamethasne in relapsed/refractry MM. Bld Nv 30;130(22): Natinal Cmprehensive Cancer Netwrk. NCCN clinical practice guidelines in nclgy (NCCN Guidelines). Acute Myelid Leukemia (Versin Nvember 30, 2018) [cited 2018 December 7]. Available frm: Natinal Cmprehensive Cancer Netwrk. NCCN clinical practice guidelines in nclgy (NCCN Guidelines). B-cell Lymphmas (Versin May 15, 2018) [cited 2018Jun 20]. Available frm: Natinal Cmprehensive Cancer Netwrk. NCCN clinical practice guidelines in nclgy (NCCN Guidelines). Chrnic Lymphcytic Leukemia/Small Lymphcytic Lymphma (Versin March 26, 2018) [cited 2018 Jun 20]. Available frm: NCCN Drugs & Bilgics Cmpendium [Internet]. Frt Washingtn (PA): Natinal Cmprehensive Cancer Netwrk; 2018 [cited 2018 December 7]. Available frm: Orphan Drug Designatins and Apprval [Internet]. Silver Spring (MD): US Fd and Drug Administratin; 2018 [cited 2018 Jun 18]. Available frm: Rberts AW, Davids MS, Pagel JM, et al: Targeting BCL2 with venetclax in relapsed chrnic lymphcytic leukemia. N Engl J Med 2016; 374(4): Rberts AW, Davids MS, Seymur JF. New Agents t Treat Chrnic Lymphcytic Leukemia. N Engl J Med Jun 2;374 (22): Seymur JF, Kipps TJ, Eichhrst B, et al. Venetclax-Rituximab in Relapsed r Refractry Chrnic Lymphcytic Leukemia. N Engl J Med Mar 22;378(12): April Seymur JF, Ma S, Brander DM, et al. Venetclax plus rituximab in relapsed r refractry chrnic lymphcytic leukaemia: a phase 1b study. Lancet Oncl Feb;18(2): Stilgenbauer S1, Eichhrst B1, Schetelig J, et al. Venetclax fr Patients With Chrnic Lymphcytic Leukemia With 17p Deletin: Results Frm the Full Ppulatin f a Phase II Pivtal Trial. J Clin Oncl May 1:JCO Stilgenbauer S, Eichhrst B, Schetelig J, et al. Venetclax in relapsed r refractry chrnic lymphcytic leukaemia with 17p deletin: a multicentre, pen-label, phase 2 study. Lancet Oncl Jun;17(6):

13 25. Venclexta (venetclax) [package insert]. AbbVie Inc. Nrth Chicag, IL, Nvember COMMITTEE APPROVAL: This Medical Cverage Guideline (MCG) was apprved by the Flrida Blue Pharmacy Plicy Cmmittee n 07/11/18. GUIDELINE UPDATE INFORMATION: 09/15/16 New Medical Cverage Guideline. 12/15/16 Revisin t guideline cnsisting f updating the descriptin sectin, psitin statement, and references based n updated NCCN guidelines fr CLL/SLL. 02/15/17 Revisin t guideline cnsisting f updating the descriptin sectin, psitin statement, billing/cding, and references based n updated NCCN guidelines fr B-cell lymphmas. 06/15/17 Revisin t guideline cnsisting f updating the descriptin sectin, psitin statement, and references based n updated NCCN guideline fr CLL/SLL 08/15/17 Review and revisin t guideline cnsisting f updating the descriptin sectin and references. 03/15/18 Revisin t guideline cnsisting f updating the descriptin sectin and references based n updated NCCN Guidelines fr CLL/SLL. 08/15/18 Review and revisin t guideline cnsisting f updating the descriptin sectin, psitin statement, dsage/administratin, billing/cding, and references. 01/15/19 Revisin t guideline cnsisting f updating the descriptin, psitin statement, dsage/administratin, warnings/precautins, billing/cding infrmatin, and references based n a new FDA-apprved indicatin fr AML and NCCN Guidelines update.