NCCN Flash Updates. 4th Quarter Page 1

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1 The fllwing reprt cntains NCCN Flash Updates relative t the furth quarter f 2017, listed in chrnlgical rder with the mst recent updates first. December 22, 2017 NCCN has published updates t the NCCN Clinical Practice Guidelines in Onclgy (NCCN Guidelines ), the NCCN Drugs & Bilgics Cmpendium (NCCN Cmpendium ), and NCCN Radiatin Therapy Cmpendium fr Hdgkin Lymphma. These NCCN Guidelines are currently available as Versin Classic Hdgkin Lymphma (CHL) Stage IA-IIA Favrable Disease (n bulky disease, <3 sites f disease, ESR <50, and n E-lesins): Deauville 1-4 has been changed t Deauville 1-3 and a treatment pathway fr Deauville 4 (Mderately increased uptake > liver) has been added. (HODG-3) Stage IA-IIA Favrable Disease (n bulky disease): After ABVD x 2 cycles (preference t treat with cmbined mdality therapy), additinal therapy fr Deauville 3-4 has been revised: ABVD x 2 cycles (ttal 4) + ISRT (30 Gy) (preferred fr Deauville 3) r Escalated BEACOPP x 2 cycles + ISRT (30 Gy) (preferred fr Deauville 4-5) (HODG-4) Fllwing this additinal therapy, "Cnsider PET/CT" fllwed by "ISRT (30 Gy)" has been added. (HODG-4) Stage I-II Unfavrable (Nn-Bulky) (HODG-6) After ABVD x 2 cycles and restaging, additinal therapy fr Deauville 1-2 has been revised t AVD x 4 cycles (ttal 6) ± ISRT. Additinal therapy fr Deauville 3-4 has been revised: ABVD x 2 cycles (ttal 4) (preferred fr Deauville 3) r Escalated BEACOPP x 2 cycles (preferred fr Deauville 4) Stage I-II Unfavrable (bulky mediastinal disease r >10 cm adenpathy) (HODG-7) After ABVD x 2 cycles and restaging, Deauville 1-3 has been changed t Deauville 1-2 and Deauville 4 has been changed t Deauville 3-4. Additinal therapy fr Deauville 3-4 has been revised: ABVD x 2 cycles (ttal 4) + ISRT (preferred fr Deauville 3) r Escalated BEACOPP x 2 cycles + ISRT (30 Gy) (preferred fr Deauville 4) r Escalated BEACOPP x 3 cycles Fllwing additinal therapy with ABVD x 2 cycles r Escalated BEACOPP x 2 cycles, "cnsider PET/CT" fllwed by "ISRT (30 Gy)" has been added. Fllwing Escalated BEACOPP x 3 cycles, "PET/CT" fllwed by "Escalated BEACOPP x 1 cycle" has been added. Stage III-IV Disease: Fllwing ABVD x 2 cycles and restaging, ABVD x 2 cycles (4 ttal) has been remved frm the additinal therapy ptins fr Deauville 4-5. (HODG-10) Refractry Disease (HODG-15) Maintenance therapy ptins revised After HDT/ASCR fr thse with Deauville 1-3 prir t HDT/ASCR: "Observe r Cnsider Brentuximab vedtin fr 1 y fr patients with high risk f relapse." After HDT/ASCR fr thse with Deauville 4 prir t HDT/ASCR: "Strngly cnsider Brentuximab vedtin fr 1 y fr patients with high risk f relapse." Ftnte ww has been added regarding brentuximab vedtin maintenance therapy: Patients with 2 r mre f the fllwing risk factrs are cnsidered high risk: Remissin duratin less than Page 1

2 1 year, extrandal invlvement, PET+ respnse at time f transplant, B symptms, and/r >1 salvage/subsequent therapy regimen. The fllwing ftnte has been remved, "The value f brentuximab maintenance fr a patient wh previusly received brentuximab vedtin is nt knwn. It des nt prvide a survival benefit." Fr thse with Deauville 5, "autlgus r allgeneic stem cell transplant if respnse t secndary therapy" has been added as an ptin after additinal therapy. Suspected Relapse (HODG-16) Initial stage IA-IIA (n prir RT with failure in initial sites): The secnd-line therapy recmmendatins have been revised t clarify the recmmendatin fr patients wh received abbreviated chemtherapy (3 4 cycles) withut RT, versus patients wh received full-curse chemtherapy. Ndular Lymphcyte-Predminant Hdgkin Lymphma (NLPHL) Fr CS IIIA, IVA, "bserve" has been added as a primary treatment ptin. (HODG-13) Principles f Systemic Therapy The secnd-line systemic therapy ptins have been revised. (HODG-E, 1 f 3) Brentuximab vedtin (nly fr CHL) alne r in cmbinatin with the ther secnd-line regimens Gemcitabine/bendamustine/vinrelbine has been added. (Santr A, Mazza R, Pulsni A, et al. Bendamustine in cmbinatin with gemcitabine and vinrelbine is an effective regimen as inductin chemtherapy befre autlgus stem-cell transplantatin fr relapsed r refractry Hdgkin lymphma: final results f a multicenter phase II study. J Clin Oncl 2016;34: ) The fllwing regimens have been mved t the list f Subsequent Systemic Therapy Optins (nly fr CHL) C-MOPP (cyclphsphamide, vincristine, prcarbazine, prednisne) (categry 2B) MINE (etpside, ifsfamide, mesna, mitxantrne) Mini-BEAM (carmustine, cytarabine, etpside, melphalan) Indicatins have been revised fr the fllwing subsequent therapy ptins (nly fr CHL) (HODG-E, 1 f 3) Nivlumab (fr patients previusly treated with brentuximab vedtin) (fr relapsed r refractry CHL fllwing HDT/ASCR) Pembrlizumab (fr patients previusly treated with brentuximab vedtin) (fr relapsed r refractry CHL after 3 prir lines f therapy) A new page has been added, titled Checkpint Inhibitrs. (HODG-E, 2 f 3) December 21, 2017 NCCN has published updates t the NCCN Clinical Practice Guidelines in Onclgy (NCCN Guidelines ), the NCCN Drugs & Bilgics Cmpendium (NCCN Cmpendium ), and the NCCN Guidelines with NCCN Evidence Blcks fr Chrnic Myelid Leukemia. These NCCN Guidelines are currently available as Versin Chrnic phase CML: Primary Treatment (CML-2) Bsutinib added as a treatment ptin fr any risk scre. This is a categry 1 recmmendatin. Intermediate- r high-risk scre: Niltinib recmmendatin changed frm a categry 2A t categry 1. Page 2

3 Intermediate- r high-risk scre: Dasatinib recmmendatin changed frm a categry 2A t categry 1. Ftnte d mdified: Lng-term fllw-up data frm the DASISION and ENESTnd trials and preliminary data frm the BFORE trial suggest that patients with an intermediate- r high-risk Skal r Hasfrd scre may preferentially benefit frm secnd generatin TKI (dasatinib, niltinib, r bsutinib). See Discussin fr additinal infrmatin. The Discussin sectin has been updated t reflect the changes in the algrithm. (MS-1) *Fr yur reference, the previus update (Versin ) t the NCCN Guidelines fr Chrnic Myelid Leukemia, published n Octber 19, 2017, is available at the fllwing link: NCCN has published updates t the NCCN Guidelines, NCCN Guidelines with NCCN Evidence Blcks, NCCN Cmpendium, NCCN Radiatin Therapy Cmpendium, and NCCN Imaging Apprpriate Use Criteria (NCCN Imaging AUC ) fr Nn-Small Cell Lung Cancer. These NCCN Guidelines are currently available as Versin The Discussin sectin has been updated t reflect the changes in the algrithm. (MS-1) *Fr yur reference, the previus update (Versin ) t the NCCN Guidelines fr Nn-Small Cell Lung Cancer, published n Nvember 17, 2017, is available at the fllwing link: NCCN has published updates t the fllwing NCCN Guidelines fr Patients : Melanma, Versin 2018 NCCN has published updates t the NCCN Clinical Practice Guidelines in Onclgy (NCCN Guidelines ) fr Palliative Care. These NCCN Guidelines are currently available as Versin High-risk fr persistent cmplex bereavement disrder" is listed under assessment fr Criteria fr Cnsultatin with Palliative Care Specialist with the fllwing crrespnding ftnte: "Persistent cmplex bereavement disrder is a chrnic heightened state f murning that significantly impairs functining." (PAL-8) "Educate patient/family/caregiver n patient's cnditin and risk/benefits f treatment ptins" is listed as an interventin fr patients thrughut the guideline fr all symptms. Page 3

4 Alpha adrenergic blckers and melatnin-receptr agnist are new pharmaclgic therapy ptins fr insmnia. (PAL-22) Assess decisin-making capacity and need fr surrgate decisin-maker is a new recmmendatin fr advance care planning. (PAL-29) First bullet regarding palliative sedatin mdified t include Palliative sedatin t uncnsciusness, in which the intended effect is deep sedatin, remains cntrversial. Crrespnding reference: ten Have H, Welie JV. Palliative sedatin versus euthanasia: an ethical assessment. J Pain Symptm Manage 2014;47(1): (PAL-33) Palliative Care Drug Appendix has been mdified as fllws: Insmnia (PAL-A 4 f 5) Quetiapine, mg PO at bedtime Fr phase shift disrder cnsider ramelten (8 mg 30 minutes befre bedtime) r melatnin (30 minutes befre bedtime; dsage may vary by frmulatin) Restless Legs Syndrme (PAL-A 4 f 5) Rpinirle, 0.25 mg PO 1-3 hurs befre bedtime Pramipexle, starting dse mg PO at bedtime, may require titratin May als cnsider pregabalin, carbidpa-levdpa, r lw-dse methadne with dpamine agnist; hwever, all f these medicatins are ff-label fr RLS *Fr yur reference, the previus update (Versin ) t the NCCN Guidelines fr Palliative Care, published n June 1, 2017, is available at the fllwing link: December 18, 2017 NCCN has published updates t the NCCN Radiatin Therapy Cmpendium based n updates t the fllwing NCCN Clinical Practice Guidelines in Onclgy (NCCN Guidelines ): AIDS-Related Kapsi Sarcma, Versin December 14, 2017 NCCN has published the fllwing NEW NCCN Clinical Practice Guidelines in Onclgy (NCCN Guidelines ) with NCCN Evidence Blcks : T-Cell Lymphmas: Extrandal NK/T-Cell Lymphma, Nasal Type, Versin Page 4

5 NCCN has published updates t the fllwing NCCN Guidelines with NCCN Evidence Blcks : Gastric Cancer, Versin NCCN has published NCCN Chemtherapy Order Templates (NCCN Templates ) fr Acute Lymphblastic Leukemia t reflect the currently published NCCN Guidelines fr Acute Lymphblastic Leukemia, Versin The fllwing NEW NCCN Templates have been published: ALL4a CALGB 8811 Larsn Regimen Curse I Inductin Cyclphsphamide/DAUNOrubicin/VinCRIStine/PredniSONE/Pegaspargase ALL4b CALGB 8811 Larsn Regimen Curse II Early Intensificatin Cyclphsphamide/Mercaptpurine/Cytarabine/VinCRIStine/Pegaspargase ALL4c CALGB 8811 Larsn Regimen Curse III CNS Prphylaxis and Interim Maintenance Cranial Irradiatin/Intrathecal Methtrexate/Mercaptpurine/Methtrexate ALL4d CALGB 8811 Larsn Regimen Curse IV Late Intensificatin DOXOrubicin/VinCRIStine/Dexamethasne/Cyclphsphamide/Thiguanine/Cytarabine ALL4e CALGB 8811 Larsn Regimen Curse V Prlnged Maintenance VinCRIStine/PredniSONE/Methtrexate/Mercaptpurine December 12, 2017 NCCN has published updates t the fllwing NCCN Guidelines fr Patients : Nn-Small Cell Lung Cancer, Versin 2018 NCCN has published updates t the NCCN Chemtherapy Order Templates (NCCN Templates ) fr Cervical Cancer t reflect the currently published NCCN Clinical Practice Guidelines in Onclgy (NCCN Guidelines ) fr Cervical Cancer, Versin A new regimen dsing ptin has been added t the fllwing template. References and Emetic Risk sectins have been updated accrdingly. CRV3: CISplatin/Gemcitabine Cycle infrmatin fr the fllwing template has been revised t 21- r 28-day cycle until disease prgressin r unacceptable txicity Page 5

6 CRV15: PACLitaxel Cycle infrmatin fr the fllwing templates has been revised t include with cncurrent radiatin CRV13: CISplatin with Cncurrent Radiatin CRV18: CISplatin/Flururacil with Cncurrent Radiatin The fllwing nte fr PACLitaxel has been updated in the Safety Parameters and Special Instructins sectin: This agent shuld be prepared either in glass r nn-pvc cntainers and administered thrugh nn-pvc tubing and a lw prtein binding 0.2 r 0.22 micrn in-line filter. CRV1: PACLitaxel/CISplatin CRV4: PACLitaxel/CARBOplatin CRV15: PACLitaxel CRV23: PACLitaxel Weekly CRV25: PACLitaxel/Tptecan CRV26: PACLitaxel/Tptecan + Bevacizumab CRV27: PACLitaxel/CARBOplatin + Bevacizumab The fllwing NEW nte fr CARBOplatin has been added t the Mnitring and Hld Parameters sectin: Electrlytes (eg, magnesium, ptassium) shuld be mnitred as clinically indicated. CRV4: PACLitaxel/CARBOplatin CRV14: CARBOplatin The fllwing NEW nte fr DOCEtaxel has been added t the Mnitring and Hld Parameters sectin: This agent may cause changes t fingernails and tenails including clr, texture, and shape. This is usually a reversible side effect, but shuld be mnitred thrughut treatment. CRV6: DOCEtaxel The fllwing NEW nte fr gemcitabine has been added t the Safety Parameters and Special Instructins sectin: This agent is an irritant. CRV3: CISplatin/Gemcitabine CRV20: Gemcitabine The fllwing NEW nte fr irintecan has been added t the Safety Parameters and Special Instructins sectin: This agent has multiple ptential drug-drug and/r drug-fd interactins. Review patient medical prfile and drug package insert fr specific drug and fd interactins and recmmendatins. CRV9: Irintecan NCCN has published updates t the NCCN Templates fr Vulvar Cancer t reflect the currently published NCCN Guidelines fr Vulvar Cancer, Versin A new regimen dsing ptin has been added t the fllwing template. References and Emetic Risk sectins have been updated accrdingly. VUL2: CISplatin/Flururacil with Cncurrent Radiatin Page 6

7 Cycle infrmatin fr the fllwing templates has been revised t include with cncurrent radiatin VUL1: CISplatin with Cncurrent Radiatin VUL2: CISplatin/Flururacil with Cncurrent Radiatin VUL3: Flururacil/MitMYCIN with Cncurrent Radiatin The fllwing nte fr PACLitaxel has been updated in the Safety Parameters and Special Instructins sectin: This agent shuld be prepared either in glass r nn-pvc cntainers and administered thrugh nn-pvc tubing and a lw prtein binding 0.2 r 0.22 micrn in-line filter. VUL6: PACLitaxel/CISplatin VUL8: PACLitaxel/CARBOplatin VUL10: PACLitaxel December 6, 2017 NCCN has published updates t the NCCN Clinical Practice Guidelines in Onclgy (NCCN Guidelines ) and NCCN Drugs & Bilgics Cmpendium (NCCN Cmpendium ) fr B-Cell Lymphmas. These NCCN Guidelines are currently available as Versin Fllicular Lymphma, histlgic transfrmatin t DLBCL Minimal r n prir chemtherapy prir t histlgic transfrmatin (FOLL-6) Axicabtagene cilleucel was added as an ptin after 2 chemimmuntherapy regimens including at least ne anthracycline-based r anthracenedine-based regimen, unless cntraindicated fr the fllwing indicatins: Partial respnse (PR) N respnse (NR) r prgressive disease After cmplete respnse (CR), PR, and NR r prgressive disease, "relapsed r prgressive disease" was added with a link t FOLL-7 (multiple prir therapies prir t histlgic transfrmatin) Ftnte u was revised by adding, "Axicabtagene cilleucel is nt an apprpriate treatment ptin fr patients with a CR." (Als fr FOLL-7) Ftnte w was added, "See Guidance fr Treatment f Patients with Chimeric Antigen Receptr (CAR) T-Cell Therapy (BCEL-D)." (Als fr FOLL-7) Multiple prir therapies prir t histlgic transfrmatin (FOLL-7) "Axicabtagene cilleucel, if nt previusly given was added as an ptin after 2 prir chemimmuntherapy regimens including at least ne anthracycline-based r anthracenedine-based regimen If prgressive disease after bservatin r transplant, "candidate fr additinal therapy" was added. "N respnse r prgressive disease" with an arrw t candidate fr additinal therapy was added. Ftnte y was added, "Data n transplant after treatment with axicabtagene cilleucel are nt available. HDT/ASCR is nt recmmended after axicabtagene cilleucel. Allgeneic HCT culd be cnsidered but remains investigatinal." Page 7

8 Diffuse Large B-Cell Lymphma Relapsed/refractry disease (BCEL-6) Axicabtagene cilleucel was added as an ptin fr the fllwing indicatins: Partial respnse, n respnse, r prgressive disease fllwing secnd-line therapy in patients with intentin t prceed t high-dse therapy with autlgus stem cell rescue (HDT/ASCR). Relapse 2 r greater (if nt previus given). Ftnte bb was added, "Sme NCCN Member Institutins require a cmplete metablic respnse in rder t prceed t high-dse therapy with autlgus stem cell rescue." Ftnte ee was added, "See Guidance fr Treatment f Patients with Chimeric Antigen Receptr (CAR) T-Cell Therapy (BCEL-D)." Primary Mediastinal Large B-Cell Lymphma (BCEL-B 1 f 4) Axicabtagene cilleucel was added as an ptin fr relapsed/refractry disease. Duble Hit Lymphmas (BCEL-B 3 f 4) Axicabtagene cilleucel was added as an ptin fr relapsed/refractry disease. Guidance fr Treatment f Patients with Chimeric Antigen Receptr (CAR) T-Cell Therapy (BCEL-D) Infrmatin related t axicabtagene cilleucel has been added fr Patient selectin Cytkine release syndrme management Neurlgic txicity management Prlnged cytpenias Hypgammaglbulinemia *Fr yur reference, the previus update (Versin ) t the NCCN Guidelines fr B-Cell Lymphmas, published n Nvember 15, 2017, is available at the fllwing link: NCCN has published updates t the fllwing NCCN Guidelines with NCCN Evidence Blcks : Kidney Cancer, Versin December 4, 2017 NCCN has published updates t the NCCN Clinical Practice Guidelines in Onclgy (NCCN Guidelines ) and the NCCN Drugs & Bilgics Cmpendium (NCCN Cmpendium ) fr Kidney Cancer. These NCCN Guidelines are currently available as Versin Page 8

9 After primary treatment, the fllwing was added under the heading "Adjuvant treatment" (KID-1) Fr stage I, "surveillance" Fr stage II, III "Clear cell histlgy and high-risk: Clinical trial (preferred) r Surveillance r Adjuvant sunitinib (categry 2B)" and "All thers: Clinical trial r Surveillance." Tw crrespnding ftntes were added Ftnte d, "High-risk defined as: tumr stage 3 r higher, reginal lymph-nde metastasis, r bth." Ftnte e, "Dsing f adjuvant sunitinib: 50 mg per day - 4 weeks n, 2 weeks ff fr 1 year." *Fr yur reference, the previus update (Versin ) t the NCCN Guidelines fr Kidney Cancer, published n September 7, 2017, is available at the fllwing link: The fllwing NEW NCCN Chemtherapy Order Templates (NCCN Templates ) have been published t reflect the NCCN Guidelines fr Kidney Cancer, Versin : KDN28: SUNItinib NCCN has published updates t the fllwing NCCN Guidelines with NCCN Evidence Blcks : Sft Tissue Sarcma, Versin NCCN has published updates t the NCCN Guidelines fr Preventin and Treatment f Cancer-Related Infectins. These NCCN Guidelines are currently available as Versin Preventin f Hepatitis B Virus (HBV), Hepatitis C Virus (HCV), and Human Immundeficiency Virus (HIV) Reactivatin Or Disease (INF-5) New pathway statement was added: "Cnsider screening all patients fr HBV, HCV, and HIV prir t inductin f immunsuppressive therapy (IST) r chemtherapy" 1st statement under therapy cnsideratins fr HBV was revised: "ID Cnsult with an expert in hepatitis treatment t determine pssible antiviral prphylaxis." General Recmmendatins fr Vaccinatin in Patients with Cancer (INF-7) 1st bullet, "General cmments" statement was revised: "Live viral vaccines shuld NOT be administered during chemtherapy r perids f significant immunsuppressin, such as treatment f GVHD. The safety f vaccines in patients receiving immunstimulatry drugs has nt been established." Als, a secnd sub-bullet was added: All husehld members shuld be up-t-date with vaccines. 5 th bullet, human papillmavirus (HPV) vaccinatin statement was revised: "The recmbinant 3-dse HPV vaccine shuld be ffered t patients f bth sexes up t 26 years f age." Page 9

10 Ftnte mm was added t title: Fr preventin f infectin in cancer survivrs, including vaccinatin recmmendatins, see Survivrship Guidelines. Initial Empiric Therapy fr Fever and Neutrpenia (FEV-5) "Levflxacin" was added under: "Cnsider ral antibitic therapy fr select lw-risk patients" Additins t Initial Empiric Regimen (FEV-7) Fr perirectal pain, a bullet: Cnsider entercccal cverage and crrespnding ftnte: "Entercccal clnizatin must be differentiated frm infectin. Vancmycin use must be minimized because f the risk f vancmycin resistance" were remved. Fr diarrhea, ftnte "s" was revised: "The safety f prbitics r fecal micrbita transplantatin (FMT) in this setting has nt been shwn. See Discussin sectin fr adjunctive treatments fr difficult C. difficile cases." Additins t Initial Empiric Regimen fr Lung Infiltrates (FEV-8) 1st bullet was added by cmbining 2 ther bullets: "Cnsider adding cverage fr atypical bacteria (azithrmycin, dxycycline, r flurquinlne)" Fllw-up Therapy fr Respnding Disease (FEV-11) 1st bullet was added: "Targeted treatment f dcumented infectins shuld be dne" 2nd bullet was added: "Reassessment f empiric Gram-negative therapy shuld be cnsidered" 3rd bullet was revised: "De-escalatin and duratin f antimicrbial therapy may be individualized A bullet was remved: "Initial antibitic regimen shuld generally be cntinued until neutrphil cunt is 500 cells/mcl and increasing" Antibacterial Agents: Gram-Psitive Activity (FEV-A) (1 f 4) Ftnte c abut dsing adjustments was revised: "Requires dse adjustment in patients with renal insufficiency. Dsing variatins exist based n age and ther pharmacdynamic parameters." (Als fr FEV-A 2 and 3 f 4) Antibacterial Agents: Anti-Pseudmnal (FEV-A) (2 f 4) Merpenem dse was revised: 1 2 g IV every 8 h (2 g IV every 8 h fr meningitis) Under Cmments/precautins fr cefepime and ceftazidime a bullet was remved: Increased frequency f resistance amng Gram-negative rd islates at sme centers" Under Cmments/precautins fr piperacillin/tazbactam a bullet was remved: May result in falsepsitive galactmannan. Antibacterial Agents: Other (FEV-A) (3 f 4) Aminglycsides dsing was revised: "Cnsider single lading dse in critically ill patients with individualized mnitring f levels. extended interval dsing." Trimethprim/sulfamethxazle (TMP/SMX) therapy Therapy dse was clarified: 15 mg/kg daily in divided dses every 6 8 h based n the trimethprim cmpnent" Page 10

11 2nd bullet under Cmments/Cautins was revised: "Mnitr fr renal insufficiency, myelsuppressin, hepattxicity, and hyperkalemia" Antifungal Agents: Azles, Cmments /Cautins (FEV-B) (1 f 5) 2nd bullet fr isavucnaznium sulfate was added: "May shrten QTc interval" Antifungal Agents: Azles (FEV-B) (2 f 5) 2nd bullet fr psacnazle under Cmments/Cautins was revised: "Liquid frmulatin has different dsing than tablet and shuld be administered with a full meal r liquid nutritinal supplement r an acidic carbnated beverage. Tablet is better absrbed, thugh it shuld be taken with fd." Vricnazle therapy dse was revised fr invasive aspergillsis and candidemia in nn-neutrpenic patients: Lading dse: "6 mg/kg IV r 400 mg PO q12 x 2 dses n Day 1" 6th bullet fr vricnazle under Cmments /Cautins was added: Visual disturbances and hallucinatins may ccur n therapy Empiric Amphtericin B Frmulatins (FEV-B) (3 f 5) Ftnte "e" fr lipsmal amphtericin dsing was revised: "The vast majrity f subjects in this trial had invasive aspergillsis; ptimal dsing f L-AMB fr ther mld infectins (such as mucrmycsis with 3 5 mg/kg/d IV) was as effective but less txic than 10 mg/kg/d as initial therapy fr invasive mld infectins." Antifungal Agents: Echincandins (FEV-B) (4 f 5) This page has been extensively revised. Antiviral Agents (FEV-C) (3 f 4) "Tenfvir alafenamide (TAF) 25 mg PO daily" was added as a new frmulatin under "Cmmn indicatin" The Discussin sectin has been updated t reflect the changes in the algrithm. (MS-1) Nvember 28, 2017 NCCN has published updates t the NCCN Clinical Practice Guidelines in Onclgy (NCCN Guidelines ) fr Multiple Myelma. These NCCN Guidelines are currently available as Versin The Discussin sectin has been updated t reflect the changes in the algrithm. (MS-1) *Fr yur reference, the previus update (Versin ) t the NCCN Guidelines fr Multiple Myelma, pub lished n Octber 2, 2017 is available at the fllwing link: NCCN has published updates t the fllwing NCCN Guidelines with NCCN Evidence Blcks : Page 11

12 Nn-Small Cell Lung Cancer, Versin Nvember 22, 2017 NCCN has published updates t the NCCN Clinical Practice Guidelines in Onclgy (NCCN Guidelines ) fr Cancer- and Chemtherapy-Induced Anemia. These NCCN Guidelines are currently available as Versin The Discussin sectin has been updated t reflect the changes in the algrithm. (MS-1) *Fr yur reference, the previus update (Versin ) t the NCCN Guidelines fr Cancer- and Chemtherapy- Induced Anemia, published n June 23, 2017, is available at the fllwing link: NCCN has published updates t the NCCN Clinical Practice Guidelines in Onclgy (NCCN Guidelines ), the NCCN Drugs & Bilgics Cmpendium (NCCN Cmpendium ), and the NCCN Radiatin Therapy Cmpendium fr Nn-Small Cell Lung Cancer. These NCCN Guidelines are currently available as Versin Ndule Management (DIAG-2 and DIAG-3) The management f a slid and sub-slid ndule(s) n chest CT was mdified based n the updated Fleischner criteria. MacMahn H, Naidich DP, G JM, et al. Guidelines fr management f incidental pulmnary ndules detected n CT scans: Frm the Fleischner Sciety Radilgy 2017;284: Metastatic NSCLC Sensitizing EGFR mutatin psitive Subsequent Therapy (NSCL-19) Multiple lesins; T790M-: The ptin fr PD-L1 expressin psitive was remved. Ftnte qq was mdified: "Cnsider simertinib (regardless f T790M status) r pulse erltinib fr carcinmatsis meningitis prgressive leptmeningeal disease." Ftnte tt is new t the page: "The data in the secnd-line setting suggest that immuntherapy is less effective, irrespective f PD-L1 expressin, in tumrs with an actinable mutatin." (als applies t NSCL-20, NSCL-22, NSCL-23, and NSCL-24) Metastatic NSCLC ALK rearrangement psitive Subsequent Therapy (NSCL-22) Systemic, Multiple lesins: The ptin fr PD-L1 expressin psitive was remved. Prgressin n criztinib after treatment fr Asymptmatic; Symptmatic Brain; Symptmatic, Systemic, Islated lesin: The ptin fr PDL1 expressin psitive was remved. Page 12

13 Ftnte uu was added: "Beware f flare phenmenn in a subset f patients wh discntinue ALK inhibitr. If disease flare ccurs, restart ALK inhibitr." Ftnte yy is new t the page: "If cnsidering WBRT, switch ALK inhibitr befre using WBRT." New page added t address prgressin n alectinib r ceritinib (NSCL-23) Metastatic NSCLC ROS1 rearrangement psitive (NSCL-24) First-line therapy: Ceritinib added as a treatment ptin. This is a categry 2A recmmendatin. First-line therapy: Criztinib listed as a preferred treatment ptin. Prgressin: The ptin fr PD-L1 expressin psitive was remved. Metastatic NSCLC Adencarcinma, Large Cell, NSCLC NOS (NSCL-27) Switch maintenance with pemetrexed changed frm a categry 2B t a categry 2A. Principles f Pathlgic Review extensively revised (NSCL-A) Principles f Radiatin Therapy (NSCL-C 8 f 10) Nrmal Tissue Dse-Vlume Cnstraints fr Cnventinally Fractinated RT Heart mean dse changed frm 35 t 26 Gy. Chemtherapy Regimens fr Neadjuvant and Adjuvant Therapy (NSCL-D) Chemtherapy Regimens fr Patients with Cmrbidities r Patients Nt Able t Tlerate Cisplatin; the fllwing regimens were added: Carbplatin AUC 5 day 1, gemcitabine 1000 mg/m 2 days 1, 8, every 21 days fr 4 cycles (categry 2A) Carbplatin AUC 5 day 1, pemetrexed 500 mg/m 2 day 1 fr nnsquamus every 21 days fr 4 cycles (categry 2A) Chemtherapy Regimens Used with Radiatin Therapy (NSCL-E) The fllwing were remved: Sequential Chemtherapy/RT Regimens (Adjuvant) Cisplatin 100 mg/m 2 n days 1 and 29; vinblastine 5 mg/m 2 /weekly n days 1, 8, 15, 22, and 29; fllwed by RT Paclitaxel 200 mg/m 2 ver 3 hurs n day 1; carbplatin AUC 6 ver 60 minutes n day 1 every 3 weeks fr 2 cycles fllwed by thracic RT Regimens t be used in sequential chemtherapy/rt are nw linked t NSCL-D. New sectin added t address the Principles f Mlecular and Bimarker Analysis (NSCL-G) Emerging Targeted Agents fr Patients with Genetic Alteratins (NSCL-H) HER2 mutatins Ad-trastuzumab emtansine (categry 2A) added Single-agent therapy with trastuzumab r afatinib was remved New sectin added prviding references fr Targeted Therapy fr Advanced r Metastatic Disease (NSCL-I) Page 13

14 Staging was updated t reflect the changes in the AJCC Cancer Staging Manual, Eighth Editin (2016). (ST-1 and ST-2) Table was added with a cmparisn f the descriptrs in the eighth editin f the TNM classificatin f lung cancer cmpared with the seventh editin. Reference: Rami-Prta R, Asamura H, Travis WD, Rusch VW. Lung cancer - Majr changes in the American Jint Cmmittee n Cancer Eighth Editin Cancer Staging Manual. CA Cancer J Clin 2017;67: (ST-3) The fllwing NCCN Chemtherapy Order Templates (NCCN Templates ) have been deleted t reflect the NCCN Guidelines fr Nn-Small Cell Lung Cancer Versin : NSC8 CISplatin/VinBLAStine fllwed by Radiatin NSC9 PACLItaxel/CARBOplatin fllwed by Radiatin The NCCN Radiatin Therapy Cmpendium has been updated t reflect the changes t the fllwing NCCN Guidelines: T-Cell Lymphmas, Versin Nvember 17, 2017 NCCN has published updates t the NCCN Clinical Practice Guidelines in Onclgy (NCCN Guidelines ) and the NCCN Drugs & Bilgics Cmpendium (NCCN Cmpendium ) fr Breast Cancer. These NCCN Guidelines are currently available as Versin Wrkup f clinical stages I-III (BINV-1, BINV-10, and BINV-14) added: Pregnancy test in all wmen f childbearing ptential Lcreginal treatment f clinical stage I, IIA, r IIB disease r T3,N1,M0 (BINV-3) Divided negative axillary ndes and tumr >5 cm r margins psitive, int tw pathways. Fllwing margins psitive added, Re-excisin t negative margins is preferred. If nt feasible, strngly cnsider radiatin therapy t chest wall, ± infraclavicular regin, ± supraclavicular area, ± internal mammary ndes and any part f the axillary bed at risk. It is cmmn fr radiatin therapy t fllw chemtherapy when chemtherapy is indicated. Systemic adjuvant treatment, hrmne receptr-psitive, HER2-psitive disease (BINV-5) Nde psitive (ne r mre metastases >2 mm t ne r mre ipsilateral axillary lymph ndes), added treatment ptin f adjuvant pertuzumab alng with trastuzumab (als applies t BINV-7) Ftnte ff is new: Cnsider extended adjuvant neratinib fllwing adjuvant trastuzumab-cntaining therapy in HR-psitive patients with a perceived high risk f recurrence (such as stage II-III). The benefit r txicities assciated with extended neratinib in patients wh have received pertuzumab is unknwn. Page 14

15 (als applies t BINV-13 and BINV-15) Preperative Systemic Therapy: Adjuvant therapy (BINV-13 and BINV-15) Added a new bullet Cnsider adjuvant capecitabine in patients with triple-negative breast cancer and residual invasive cancer fllwing standard neadjuvant treatment with taxane-, alkylatr-, and anthracycline-based chemtherapy. Added ptin f adjuvant pertuzumab- "If HER2-psitive, cmplete up t ne year f HER-2 targeted therapy with trastuzumab (categry 1) ± pertuzumab. HER2-targeted therapy may be administered cncurrently with radiatin therapy and with endcrine therapy if indicated." Recurrent/Stage IV disease (BINV-17) Added, Discuss gals f therapy, adpt shared decisin-making, and dcument curse f care t the wrkup. Treatment f Recurrent/Stage IV disease, separated treatment algrithms based n hrmne receptr status, HER2 status, and prir endcrine therapy. (BINV-19) Systemic treatment f Recurrent/Stage IV disease, ER and/r PR psitive; HER2 negative (BINV-20) N prir endcrine therapy within 1 y, pstmenpausal: Changed "Palbciclib + letrzle armatase inhibitr (categry 1)" Changed "Ribciclib + letrzle armatase inhibitr (categry 1)" Systemic treatment f Recurrent/Stage IV disease, ER and/r PR psitive; HER2 negative (BINV-21) Mdified ftnte hhh, If there is disease prgressin while n a CDK4/6 inhibitr + an armatase inhibitr letrzle, there are n data t supprt an additinal line f therapy with anther palbciclib CDK4/6-cntaining regimen. Likewise, if there is disease prgressin while n an everlimus-cntaining regimen, there are n data t supprt an additinal line f therapy with anther everlimus regimen. Principles f radiatin therapy (BINV-I) The whle breast shuld receive a dse f Gy in fractins r Gy in fractins (hypfractinatin is preferred). "Dse is Gy in fractins t the chest wall +/- scar bst at Gy per fractin t a ttal dse f apprximately 60 Gy." Preperative/adjuvant therapy regimens (BINV-K) Remved the fllwing regimens and crrespnding dsing: FEC (flururacil/epirubicin/cyclphsphamide) fllwed by dcetaxel + trastuzumab + pertuzumab FEC fllwed by paclitaxel + trastuzumab + pertuzumab Pertuzumab + trastuzumab + dcetaxel fllwed by FEC Pertuzumab + trastuzumab + paclitaxel fllwed by FEC Systemic therapy fr ER and/r PR-psitive Recurrent r Stage IV disease (BINV-N) Separated treatment algrithms based n HER2-status. Pstmenpausal and HER2-negative, added: Everlimus + fulvestrant Everlimus + tamxifen Page 15

16 Abemaciclib + fulvestrant (categry 1) with ftnte Indicated after prgressin n prir endcrine therapy Abemaciclib with ftnte "Indicated after prgressin n prir endcrine therapy and prir chemtherapy in the metastatic setting." Pstmenpausal and HER2-negative, changed: Palbciclib + letrzle armatase inhibitr (categry 1) Ribciclib + letrzle armatase inhibitr (categry 1) NCCN Categry f fulvestrant frm 2A t 1 Premenpausal and HER2-psitive, added: Tamxifen ± trastuzumab Ovarian ablatin r suppressin plus therapy as fr pst-menpausal wmen. Pstmenpausal and HER2-psitive, added: Armatase inhibitr ± trastuzumab Armatase inhibitr ± lapatinib Armatase inhibitr ± lapatinib + trastuzumab Fulvestrant ± trastuzumab Tamxifen ± trastuzumab. Chemtherapy regimens fr recurrent r metastatic breast cancer (BINV-O) Added Olaparib (ptin fr HER2-negative, BRCA 1/2-psitive tumrs) with a ftnte, "Patients with HER2-negative disease eligible fr single-agent therapy are eligible fr germline BRCA 1/2 testing." *Fr yur reference, the previus update (Versin ) t the NCCN Guidelines fr Breast Cancer, published n April 16, 2017, is available at the fllwing link: The fllwing NCCN Chemtherapy Order Templates (NCCN Templates ) have been deleted t reflect the NCCN Guidelines fr Breast Cancer Versin : Preperative/Adjuvant Therapy Regimens BRS94a: FEC (Flururacil/EPIrubicin/Cyclphsphamide) fllwed by Pertuzumab + Trastuzumab + DOCEtaxel FEC (Flururacil/EPIrubicin/Cyclphsphamide) Curse BRS94b: FEC (Flururacil/EPIrubicin/Cyclphsphamide) fllwed by Pertuzumab + Trastuzumab + DOCEtaxel Pertuzumab + Trastuzumab + DOCEtaxel Curse BRS95a: FEC (Flururacil/EPIrubicin/Cyclphsphamide) fllwed by Pertuzumab + Trastuzumab + PACLItaxel FEC (Flururacil/EPIrubicin/Cyclphsphamide) Curse BRS95b: FEC (Flururacil/EPIrubicin/Cyclphsphamide) fllwed by Pertuzumab + Trastuzumab + PACLItaxel Pertuzumab + Trastuzumab + PACLItaxel Curse BRS97a: Pertuzumab + Trastuzumab + DOCEtaxel fllwed by FEC (Flururacil/EPIrubicin/Cyclphsphamide) fllwed by Trastuzumab - Pertuzumab + Trastuzumab + DOCEtaxel Curse BRS97b: Pertuzumab + Trastuzumab + DOCEtaxel fllwed by FEC (Flururacil/EPIrubicin/Cyclphsphamide) fllwed by Trastuzumab - FEC (Flururacil/EPIrubicin/Cyclphsphamide) Curse Page 16

17 BRS98a: Pertuzumab + Trastuzumab + PACLItaxel fllwed by FEC (Flururacil/EPIrubicin/Cyclphsphamide) fllwed by Trastuzumab - Pertuzumab + Trastuzumab + PACLItaxel Curse BRS98b: Pertuzumab + Trastuzumab + PACLItaxel fllwed by FEC (Flururacil/EPIrubicin/Cyclphsphamide) fllwed by Trastuzumab - FEC (Flururacil/EPIrubicin/Cyclphsphamide) Curse NCCN has published updates t the NCCN Templates fr Melanma t reflect the currently published NCCN Guidelines fr Melanma Versin The fllwing NEW NCCN Templates have been published: MEL3: CISplatin/VinBLAStine/Dacarbazine/Aldesleukin (Interleukin-2)/Interfern alfa MEL23: High Dse Ipilimumab MEL24: Ipilimumab + Nivlumab MEL25: Vemurafenib/Cbimetinib MEL26: Intralesinal Aldesleukin (interleukin-2) MEL27: Intralesinal BCG (Bacillus Calmette-Guérin) MEL28: Intralesinal Interfern alfa-2b MEL29: Intralesinal Talimgene laherparepvec MEL30: Tpical Imiquimd Indicatins fr the fllwing NCCN Templates have been updated: MEL1: Dacarbazine MEL4: High-Dse Aldesleukin (Interleukin-2) MEL5: Temzlmide MEL7: PACLitaxel MEL9: PACLitaxel/CARBOplatin MEL12: High-Dse Interfern alfa-2b MEL13: PEGinterfern alfa-2b MEL14: Ipilimumab MEL15: Vemurafenib MEL16: Imatinib MEL17: Dabrafenib MEL19: Albumin-bund PACLitaxel MEL20: Pembrlizumab MEL21: Dabrafenib/Trametinib MEL22: Nivlumab Cycle infrmatin fr the fllwing templates has been updated t a ttal f 1 year f therapy in the adjuvant setting MEL12: High-Dse Interfern alfa-2b MEL21: Dabrafenib/Trametinib MEL22: Nivlumab The fllwing NEW nte fr nivlumab and pembrlizumab has been added t the Other Supprtive Therapy sectin: This agent may cause new nset type 1 diabetes mellitus with ketacidsis. Bld glucse shuld be mnitred prir t each dse and as clinically indicated. Mdificatin r discntinuatin f therapy Page 17

18 may be warranted. Patients may require insulin replacement therapy accrding t specific recmmendatins in the drug package insert. MEL20: Pembrlizumab MEL22: Nivlumab The fllwing NEW nte fr nivlumab and pembrlizumab has been added t the Mnitring and Hld Parameters sectin: Serum glucse shuld be mnitred prir t each dse and as clinically indicated. MEL20: Pembrlizumab MEL22: Nivlumab NCCN has published updates t the NCCN Templates fr Cervical Cancer t reflect the currently published NCCN Guidelines fr Cervical Cancer v The fllwing NEW NCCN Templates have been published: CRV27: PACLitaxel/CARBOplatin + Bevacizumab CRV28: Albumin-bund PACLitaxel CRV29: Pembrlizumab NCCN has published updates t the NCCN Templates fr Vulvar Cancer t reflect the currently published NCCN Guidelines fr Vulvar Cancer v The fllwing NEW NCCN Templates have been published: VUL7: CARBOplatin VUL8: PACLitaxel/CARBOplatin VUL9: Erltinib VUL10: PACLitaxel VUL11: CISplatin/Gemcitabine VUL12: Pembrlizumab NCCN has published updates t the NCCN Templates fr Occult Primary t reflect the currently published NCCN Guidelines fr Occult Primary v The fllwing NEW nte fr carbplatin has been added t the Mnitring and Hld Parameters sectin: Electrlytes (eg, magnesium, ptassium) shuld be mnitred as clinically indicated. OCP1: PACLitaxel/CARBOplatin OCP2: PACLitaxel/CARBOplatin/Oral Etpside OCP3: DOCEtaxel/CARBOplatin OCP13: DOCEtaxel/CARBOplatin OCP17: Irintecan/CARBOplatin Page 18

19 The fllwing NEW nte fr dcetaxel has been added t the Mnitring and Hld Parameters sectin: This agent may cause changes t fingernails and tenails including clr, texture, and shape. This is usually a reversible side effect, but shuld be mnitred thrughut treatment. OCP3: DOCEtaxel/CARBOplatin OCP5: Gemcitabine/DOCEtaxel OCP7: DOCEtaxel/CISplatin/Flururacil OCP13: DOCEtaxel/CARBOplatin OCP14: DOCEtaxel/CISplatin OCP16: DOCEtaxel/CISplatin The fllwing NEW nte fr gemcitabine has been added t the Safety Parameters and Special Instructins sectin: This agent is an irritant. OCP4: Gemcitabine/CISplatin OCP5: Gemcitabine/DOCEtaxel OCP18: Irintecan/Gemcitabine The fllwing NEW nte fr irintecan has been added t the Safety Parameters and Special Instructins sectin: This agent has multiple ptential drug-drug and/r drug-fd interactins. Review patient medical prfile and drug package insert fr specific drug and fd interactins and recmmendatins. OCP17: Irintecan/CARBOplatin OCP18: Irintecan/Gemcitabine Nvember 16, 2017 NCCN has published updates t the NCCN Clinical Practice Guidelines in Onclgy (NCCN Guidelines ), and NCCN Drugs & Bilgics Cmpendium (NCCN Cmpendium ) fr B-Cell Lymphmas. These NCCN Guidelines are currently available as Versin Mantle Cell Lymphma Secnd-line Therapy (MANT-A 1 f 3) Acalabrutinib was added as an ptin with a categry 2A recmmendatin alng with a crrespnding ftnte: The phase 2 ACE-LY-004 study excluded patients treated with Brutn s tyrsine kinase (BTK) r BCL-2 inhibitr and cncmitant warfarin r equivalent vitamin K antagnists." Special Cnsideratins fr the Use f Small-Mlecule Inhibitrs (NHODG-E) Infrmatin regarding acalabrutinib was added including dsage, special cnsideratins and cadministratin with CYP3A inhibitrs and inducers. *Fr yur reference, the previus update (Versin ) t the NCCN Guidelines fr B-Cell Lymphmas, published n September 26, 2017, is available at the fllwing link: Page 19

20 NCCN has published updates t the NCCN Guidelines fr Clrectal Cancer Screening. These NCCN Guidelines are currently available as Versin The Discussin sectin has been updated t reflect the changes in the algrithm. (MS-1) *Fr yur reference, the previus update (Versin ) t the NCCN Guidelines fr Clrectal Cancer Screening, published n May 22, 2017, is available at the fllwing link: Nvember 13, 2017 NCCN has published updates t the NCCN Clinical Practice Guidelines in Onclgy (NCCN Guidelines ), the NCCN Drugs & Bilgics Cmpendium (NCCN Cmpendium ), and the NCCN Radiatin Therapy Cmpendium fr Primary Cutaneus B-Cell Lymphmas. These NCCN Guidelines are currently available as Versin Primary Cutaneus Marginal Zne Lymphma r Fllicle Center Lymphma (CUTB-3) Rituximab and hyalurnidase human injectin fr subcutaneus use is included as an ptin with the fllwing ftnte: Rituximab and hyalurnidase human injectin fr subcutaneus use may be substituted fr rituximab after patients have received the first full dse f rituximab by intravenus infusin. This substitutin cannt be made fr rituximab used in cmbinatin with ibritummab tiuxetan. A new Principles f Radiatin Therapy was added. (CUTB-C) NCCN has published updates t the NCCN Clinical Practice Guidelines in Onclgy (NCCN Guidelines ) fr Ovarian Cancer. These NCCN Guidelines are currently available as Versin The Discussin sectin has been updated t reflect the changes in the algrithm. (MS-1) *Fr yur reference, the previus update (Versin ) t the NCCN Guidelines fr Ovarian Cancer, published n August 30, 2017, is available at the fllwing link: Nvember 10, 2017 Page 20

21 NCCN has published updates t the NCCN Clinical Practice Guidelines in Onclgy (NCCN Guidelines ), NCCN Imaging Apprpriate Use Criteria (NCCN Imaging AUC ), and NCCN Radiatin Therapy Cmpendium fr Occult Primary (Cancer f Unknwn Primary [CUP]). These NCCN Guidelines are currently available as Versin Suspected Metastatic Malignancy (OCC-1) Symptm-directed endscpy was changed t Clinically-directed endscpy, as indicated. Cre needle bipsy (preferred) and/r FNA with cell blck f mst accessible site. Pathlgic Diagnsis (OCC-2) Lcalized has been added t adencarcinma r carcinma nt therwise specified thrughut the guidelines. Lcalized adencarcinma / Supraclavicular Ndes (OCC-3) Men and wmen: Endscpy, if clinically indicated is new t the page. Tumr-Specific Markers and their Staining Pattern (OCC-A) The Immunhistchemistry Markers sectin f the guidelines has been extensively mdified. Principles f Radiatin Therapy (OCC-C) Palliative Therapy, mdified as fllws: Regimen: A number f hypfractinatin regimens culd be cnsidered, but typically 8 Gy in 1 fractin, 20 Gy in 4 5 fractins, r 30 Gy in 10 fractins are mst frequently used. NCCN has published updates t the NCCN Chemtherapy Order Templates (NCCN Templates ) fr Chrnic Lymphcytic Leukemia/Small Lymphcytic Lymphma (CLL/SLL) t reflect the currently published NCCN Guidelines fr CLL/SLL, Versin Indicatins fr the fllwing NCCN Templates have been updated: CLL14 FR (Fludarabine + RiTUXimab) CLL24 CHOP (Cyclphsphamide/DOXOrubicin/VinCRIStine/PredniSONE) + RiTUXimab CLL28 OFAR (OXALIplatin/Fludarabine/Cytarabine + RiTUXimab) Prednisne dsing and references fr the fllwing NCCN Template have been updated: CLL24 CHOP (Cyclphsphamide/DOXOrubicin/VinCRIStine/PredniSONE) + RiTUXimab New nte fr muccutaneus reactins secndary t RiTUXimab has been added t the Mnitring and Hld Parameters sectin fr the fllwing NCCN Templates: CLL14 FR (Fludarabine + RiTUXimab) CLL24 CHOP (Cyclphsphamide/DOXOrubicin/VinCRIStine/PredniSONE) + RiTUXimab CLL28 OFAR (OXALIplatin/Fludarabine/Cytarabine + RiTUXimab) Page 21

22 Administratin instructins fr RiTUXimab have been updated n the fllwing NCCN Template: CLL14 FR (Fludarabine + RiTUXimab) New nte fr liver mnitring fr cytarabine has been added t the Mnitring and Hld Parameters sectin fr the fllwing NCCN Template: CLL28 OFAR (OXALIplatin/Fludarabine/Cytarabine + RiTUXimab) Nvember 9, 2017 NCCN has published updates t the NCCN Clinical Practice Guidelines in Onclgy (NCCN Guidelines ) and the NCCN Drugs & Bilgics Cmpendium (NCCN Cmpendium ) fr T-Cell Lymphmas. These NCCN Guidelines are currently available as Versin Peripheral T-Cell Lymphmas (PTCL) Subtypes, "Ndal peripheral T-cell lymphma with TFH phentype" and "Fllicular T-cell lymphma" were added. (TCEL-1) ALCL, ALK psitive, Stage I, II (TCEL-3) First-line therapy, "Multiagent chemtherapy x 3 4 cycles + ISRT (30 40 Gy)" was changed frm a categry 2A t a categry 2B. After first-line therapy, "Interim restaging with PET/CT r C/A/P CT scan with cntrast" was added and the ptins fr "Cmplete r partial respnse" and "Prgressive r refractry disease" were added. All ther subtypes, Stage I-IV (TCEL-4) After first-line, "Interim restaging with PET/CT r C/A/P CT scan with cntrast" was added and the ptins fr "Respnding disease" and "Prgressive r refractry disease" were added. Relapsed/refractry disease, n intentin t transplant (TCEL-5) Best supprtive care was added as an ptin. Respnse assessment after secnd-line therapy was added with ptins fr "cmplete r partial respnse" and "n respnse". Tw additinal prgnstic indices were added (TCEL-A) Prgnstic Index fr PTCL-U (mdified-pit) Internatinal T-Cell Lymphma Prject Suggested treatment regimens First-line therapy ALCL, ALK+ histlgy Dse-adjusted EPOCH was added. Other histlgies (ALCL, ALK-; PTCL, NOS; AITL; EATL; MEITL; Ndal PTCL, TFH; FTCL) Other recmmended regimens, HyperCVAD was changed frm a categry 2A t a categry 3 recmmendatin. Secnd-line and Subsequent Therapy fr ALCL (TCEL-B 4 f 5) Brentuximab vedtin was added as the "preferred regimen" fr bth with intentin and n intentin t transplant. Page 22

23 Criztinib (ALK+ ALCL nly) was added as an ptin under ther recmmended single agents fr bth with intentin and n intentin t transplant. Breast Implant-Assciated ALCL Adjuvant treatment (BIAA-2) RT dse was added as Gy. The Prpsed TNM Staging fr Breast Implant-Assciated Anaplastic Large-Cell Lymphma was added t the algrithm. (BIAA-B) Mycsis Fungides/Sezary Syndrme Stage IV (MFSS-9) Sezary syndrme Fr Refractry disease t multiple previus therapies r prgressin, "Cnsider allgeneic HCT, as apprpriate" was added. Nn Sezary r visceral disease Fr Refractry disease t multiple previus therapies r prgressin, "Cnsider allgeneic HCT, as apprpriate" was added. Suggested Treatment Regimens (MFSS-A) Systemic therapies, brentuximab vedtin was added t Categry A (SYST-CAT A) as a categry 2A recmmendatin with the fllwing ftnte: "A randmized phase 3 trial cmparing brentuximab vedtin (BV) with physician s chice f ral bexartene r methtrexate, shwed superir clinical utcme f BV in patients with CD30+ MF and pcalcl. CD30 psitivity was defined as CD30 expressin >10% f ttal lymphid cells in at least 1 f minimal 2 skin bipsies required t evaluate fr eligibility. Frty-fur percent f eligible patients with MF had at least 1 screening skin bipsy with CD30 <10%. In the tw previusly reprted investigatr-initiated studies, clinical respnses with BV was bserved acrss all CD30 expressin levels including in thse with negligible CD30 expressin." Principles f Radiatin Therapy fr MF/SS was added. (MFSS-C) Primary Cutaneus CD30+ T-Cell Lymphprliferative Disrders Primary cutaneus ALCL (PCTLD-4) Multifcal lesins, the primary treatment recmmendatins were separated int "preferred" and "ther" Brentuximab vedtin was listed as "preferred" and was changed frm a categry 2A t a categry 1 recmmendatin. The remaining primary treatment ptins are listed under "ther recmmended regimens." Cutaneus ALCL with reginal nde, the primary treatment recmmendatins were separated int "preferred" and "ther" Brentuximab vedtin ± ISRT was listed as "preferred." The remaining primary treatment ptins are listed under "ther recmmended regimens." Lymphmatid papulsis (PCTLD-5) Page 23

24 Limited lesins was separated int "Limited lesins, asymptmatic" and "Limited lesins, symptmatic." After primary treatment, "asymptmatic disease" was changed t "respnse" and "symptmatic disease" was changed t "N respnse/refractry disease." Fr relapsed/refractry disease after respnse, "cntinue bservatin" was changed t "Cntinue current management" and "tpical sterids" was remved. Fr relapsed/refractry disease after n respnse/refractry disease, "clinical trial" was added as an ptin. T-Cell Prlymphcytic Leukemia Primary Treatment (TPLL-2) Intravenus alemtuzumab alne is listed as a preferred ptin. FMC fllwed by IV alemtuzumab and IV alemtuzumab and pentstatin are recmmended fr selected patients. Extrandal NK/T-Cell Lymphma, nasal type Inductin therapy, Nasal, Stage I-II (NKTL-3) Fr patients fit fr chemtherapy, the last inductin therapy ptin was revised as, "Sandwich chemradiatin in selected patients." Pst-RT Evaluatin (Nasal, Stage I,II and Stage IV; Extranasal, stage I-IV), (NKTL-4) Respnse t therapy: "Refractry disease" was changed t "N respnse." Additinal therapy: "Secnd-line chemtherapy (pegaspargase-based)" was clarified as "cmbinatin chemtherapy regimen (asparaginase-based)" Clinical trial (preferred) and Pembrlizumab were added as ptins fr relapsed/refractry disease fllwing secnd-line therapy with asparaginase-based regimens. Ftnte q was added t pembrlizumab, "Clinical trial is the preferred relapsed/refractry ptin. In the absence f a clinical trial, pembrlizumab is an apprpriate ptin." Supprtive Care Tumr Lysis Syndrme (LYMP-A 1 f 2) Labratry hallmarks f TLS, "elevated creatinine" was added. Anti-CD52 Antibdy Therapy: Alemtuzumab, three bullets were added: (LYMP-A 2 f 2) Herpes virus prphylaxis with acyclvir r equivalent PJP prphylaxis with sulfamethxazle/trimethprim r equivalent Cnsider antifungal prphylaxis Principles f Radiatin Therapy (LYMP-C 3 f 4) General dse guidelines, "RT in cnventinal fractin sizes" was added t the heading. 3rd bullet, dsing fr primary cutaneus anaplastic large cell lymphma was revised frm "30 36 Gy" t "24 36 Gy. Nvember 3, 2017 Page 24