Clinical Immunotherapy Guidelines: An Update

Society for Immunotherapy of CancerNovember 2011Bethesda, MD

CIG Project Development (to date)

ember 2009 Concept proposed to SITC Board of Director

mer 2010 Concept developed internally with SITC leadership

ber 2010 Plans for CIG project presented to SITC membersh

ary 2011 Discussions with Dr. Arlene Fink (UCLA, RAND)

ch 2011 Steering Committee established for Melanoma TaskForce

2011 Melanoma Task Force faculty identified and invited

2010 Steering Committee develops meeting agenda/cont

Clinical Immunotherapy uidelines: Melanoma Task Forc

Society for Immunotherapy of CancerThursday June 2, 2011

University Club of Chicago

IOM Standards for Developing Trustworthy Clinical Practice Guideline

andard 1 Establishing transparencyandard 2 Management of COIandard 3 Guidelines for development of group

compositionandard 4 Clinical practice guideline-systematic

review intersectionandard 5 Establishing evidence foundations for an

rating strength of recommendationsandard 6 Articulation of recommendationsandard 7 External reviewandard 8 Updating

CIG Melanoma Task Force Steering Committee

Michael T. Atkins, MD

F. Steven Hodi, MD

Howard L. Kaufman, MD

John Kirkwood, MD

Melanoma Task Force

atient Eligibility

oxicity Assessment and Management

Response Assessment and Stopping

reatment Combinations and Sequencing

Faculty Participants

anjiv Agarwala, MD, St. Luke’s Cancer Center

om Amatruda, MD, Humphrey Cancer Center

ike Atkins, MD, Beth Israel Deaconess

even Bines, MD, Rush University

oe Clark, MD, Loyola University

rendan Curti, MD, Providence Cancer Center

arc Ernstoff, MD, Dartmouth

homas Gajewski, MD, PhD, Univ. of Chicago

ene Gonzalez, MD, University of Colorado

Stephen Hodi, MD, Dana Farber Cancer Center

atrick Hwu, MD, MD Anderson

aura Jane Hyde, Gilda’s Club

oward Kaufman, MD, Rush University

ohn Kirkwood, MD, Univ. of Pittsburgh

avid Lawson, MD, Emory University

Jose Lutzky, MD, Mt. Sinai Medical Center

Kim Margolin, MD, Univ. of Washington

David McDermott, MD, Harvard Cancer Center

Donald Morton, MD, John Wayne Cancer Institute

Anna Pavlick, DO, NYU

Jon M. Richards, MD, PhD, Lutheran General Ho

Doug Schwartzentruber, MD, Goshen Cancer Ce

Bill Sharfman, MD, Johns Hopkins University

Vern Sondak, MD, H. Lee Moffitt Cancer Center

Jeff Sosman, MD, Vanderbilt University

Susan Steel, Skin of Steel

Ahmad Tarhini, MD, University of Pittsburgh

John Thompson, MD, University of Washington

Jill Titze, NP, Rush University

Walter Urba, MD, PhD, Providence Cancer Cente

Richard White Jr MD Carolinas Medical Center

General Task Force SlidesFaculty Responses

Status of Immunotherapy for Melanoma

John Kirkwood, MDUniversity of Pittsburgh

Patient Eligibility

Mike Atkins, MDBeth Israel Deaconess Medical

Center

Patient Eligibility

Who should receive adjuvant interferon?Who should receive pegylated interferon?Who should undergo surgical resection fortage IV disease?

Who should receive high-dose IL-2?Who should receive ipilumimab?Who should receive chemotherapy?Who should receive a BRAFinhibitor?

Therapy

geerformance statuso-morbiditiestagelceration of primaryentinel Node Statusite of primary (mucosal, ALM etc)

Stage IV Therapy

tes of metastasesSoft tissueLungCNSumber of metastatic sitesDH statusRAF mutation statusRAS mutational statusKit mutational status

mmune infiltrationDL1 expression

Toxicity Assessment and ManagementJohn Kirkwood, MD

University of Pittsburgh

Toxicity Assessment and Managemen

terferonHepatic toxicityHematologic toxicityNeuropsychiatric toxicityEndocrine and other autoimmune effectsterleukin-2Capillary leak syndromeManagement of autoimmune hypothyroidismilimumabAutoimmune toxicityacarbazine

Considerations for Toxicity

ime course of anticipated toxicityndications for dose reduction/holdingndications for supportive interventionsndications for stopping treatment ermanentlyiomarker functions of autoimmune and ther ‘toxicity’ events

Response Assessment and Treatment Cessation

F. Stephen Hodi, MDDana Farber Cancer Center

Response Assessment

What is the best measure of clinical response?the presence of partial response, when do you

ontinue current treatment?the presence of stable disease, when do you

ontinue current treatment?the presence of progressive disease, when do yo

ontinue current treatment?What imaging modalities should be used to define

sponses with immunotherapy?

Treatment Combinations and Sequencing

Howard L. Kaufman, MDRush University

reatment Combination and Sequencin

ocus on Stage IV melanomaonsider agents in clinical development

eatment options for Stage IV Melanom

acarbazineterleukin-2ilimumab

RAF inhibitors (CKIT, MEK, etc.)EGF inhibitorsnti-PD1 antibodyVD/CVT chemotherapyarboplatin/Taxol chemotherapyochemotherapy

eatment Combinations and Sequencin

re there any combination immunotherapy regimens that ce recommended?hat are the priorities for clinical testing of combination

mmunotherapy?hen should IL-2 be first-line treatment?hen should ipilimumab be first-line treatment?hen should dacarbazine/temozolomide be first-line

eatment?hen should a clinical trial be first-line treatment?hen should metastasectomy be considered?hat parameters should be considered in sequencing of

?

Consideration in TreatmentCombinations and Sequencing

atient-specific factorsperformance statusageLDHumor-specific factorsBRAF status (or others)CNS diseaseTumor doubling timehysician-specific factorsImmunotherapy expertise

DRAFT CLINICAL MMUNOTHERAPY GUIDELINESFOR MALIGNANT MELANOMA

Stage II Melanoma

Pegylated –Interferon•Clinical benefit

•Indications

Observation

Interferon - α•Clinical benefit

•Indications

Clinical Trial•Clinical benefit

•Indication

•Performance status•Psychiatic history

•Autoimmunity

•Performance status•Psychiatric history

•Autoimmunity

•Disease recurrence/re-

staging

•Constitutional•Neutropenia

•Thrombocytopenia•Hepatic toxicity

•Depression•Autoimmunity

•Cosntitutional•Neutropenia

•Thrombocytopenia•Hepatic toxicity

•Depression•Autoimmunity

•Disease•To

ationsager depthrationosesansit

•Disease•To

Treatment Selection

Patient Selection

Treatment Toxicity

PatCess

•Protocol specific

Stage III Melanoma

Pegylated –Interferon•Clinical benefit

•Indications

Observation

Interferon - α•Clinical benefit

•Indications

Clinical Trial• Clinical benefit

•Indication

•Performance status•Psychiatric history

•Autoimmunity

•Performance status•Psychiatric history

•Autoimmunity

•Disease recurrence/re-

staging

•Constitutional •Neutropenia

•Thrombocytopenia•Hepatic toxicity

•Depression•Autoimmunity

•Constitutional•Neutropenia

•Thrombocytopenia•Hepatic toxicity

•Depression•Autoimmunity

•Disease•To

ationsager depthrationosesstatus

•Disease•To

Treatment Selection

Patient Selection

Treatment Toxicity

PatCess

•Protocol specific

Stage IV Melanoma

Surgery•Clinical benefit

•Indications

•Location•Resectability

•Medical comorbidity•Access to expertise

•Performance status•Medical fitness

•Age•CNS disease

•Access to expertise

•Post-operative complications•Anesthetic

complications

•Follow-•Use o

th

ationsc locationnce statusomorbitieso experts

•Diseas•Drug

Treatment Selection

Patient Selection Treatment

ToxicityPat

Cess

Interleukin-2•Clinical benefit

•Indications

Ipilimumab•Clinical benefit

•Indications

Vemurafenib•Clinical benefit

•Indications

Clinical Trial•Clinical benefit

•Indications

Observation/Palliation

•Clinical benefit•Indications

Chemotherapy

•Performance status•Medical fitness

•Age•CNS disease

•Access to expertise

•Skin rash•Diarrhea

•Hepatic toxicity•Endocrinopathy

•Neuropathy

•Skin toxicity•Diarrhea•Fatigue

•Arthralgia

•Protocol specific

•Disease progression

•Palliation toxicity•Psychosocial

distress

•Diseas•Drug

•Diseas•Drug

•Diseas•Drug

•Diseas•Patient

•Performance status•Medical fitness

•Age•CNS disease•BRAF Status

•Performance status•Medical fitness

•Age•CNS disease

•Access to expertise

•Performance status•Medical fitness

•Age•CNS disease

•Access to expertise

•Performance status•Medical fitness

See Slide 4

Stage IV Melanoma

ukin-2

Treatment Toxicity

Pulmonary toxicity

Cardiac toxicity

CNS toxicity

Vascular leak syndrome

GI/Hepatic toxicity

Renal toxicity

Hematologic toxicity

Endocrine toxicity

Autoimmunity

Ski t i it

Stage IV Melanoma

Dacarbazine1

therapy

Treatment Selection

Temozolomide1

Cis-platinum2

VinblastineDacarbazine/Temozolomide

Carboplatinum2

Paclitaxel

Biochemotherapy2

Other

Next Steps

terature review and supporting documentation

ectronic questionnaire to Melanoma Task Force Members

onsensus draft statement prepared

onsensus presented to SITC membership

btain feedback from external peer review

raft manuscript prepared

anuscript submitted for publication

Thank You!

r. Thomas Gajewski and SITC Boardr. Arlene Fink, UCLA/RAND Corporationara Withington, CAE and SITC staffelanoma Steering Committeeelanoma Task Force Faculty Participants