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The Nuts and Bolts of Doing it: Setting Up�Immune Effector Therapy in Community�Oncology Practice

Tara M Graff DO MS

Medical Oncologist

Director of Clinical Trials for Mission Cancer and Blood/UIHSMG

Director of Cellular Therapy ONCare Alliance

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Disclosures

  • AbbVie
  • Adaptive Biotechnologies
  • ADC Therapeutics
  • Astra-Zeneca
  • BMS
  • Beigene
  • Cellectar
  • Genentech
  • Genmab
  • Gilead/Kite
  • Lilly
  • MorphoSys
  • Pfizer

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Approaches to Lymphoma Immune Effector�Therapies; Guidance for Community�Oncology Practices

So how do we do it?

This Photo by Unknown Author is licensed under CC BY

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Bispecific Planning (Building Blocks)

Bispecific management team

    • Patient, Caregiver, Nurse Champions, APP, Physician, Pharmacist, hospital system
    • Learning from like minded centers
    • Mock patient
    • Inservice by experienced physician/treatment center

Bispecific Needs (depends on which agent used)

    • Outpatient vs inpatient administration, timing for monitoring
    • Concise Management Plan
    • Plan for “Team” and patient/caregiver
    • All patients to have BP cuff, thermometer, Pulse Ox – and know how to use them (reach out to companies)
    • Checklist for starting a patient

Facility Management/Logistics

    • Communication with hospital system (ER, floors, on-call team, pharmacy)
    • Need for supportive meds (Toci, Anakinra, etc)
    • Who has what---keeper of the “drugs”
    • 2 doses of Toci at all locations (per patient)
    • How do you want to manage—**capabilities
    • Patient no more than 30-60 min of nearest hospital or clinic with Toci stock

APP, advanced practice provider; BP, blood pressure; ER, emergency room; Toci, tocilizumab.

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Key Elements

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  • Bispecific Team
  • Concise management plan (outpatient vs inpatient)
  • Order sets initiated on inpatient side for CRS and ICANS
  • Ongoing education; in services
  • Cooperation between clinic and hospital system/staff

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Bispecific Team

  • Roles
  • Knowledge/education
  • Prepare for every scenario
  • Take ownership

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Bispecific Team

  • Tara Graff, DO MS
  • Jane Osterson, COO
  • Marcy Budish, Co-Director Chemotherapy Infusion
  • Wendy Kralik, Co-Director Chemotherapy Infusion
  • Corey Wilson, Director of Pharmacy
  • Maddie Koppin, Clinical Oncology Pharmacist
  • Amy Raedeker, APP Program Director
  • Brooke Walter, RN
  • Michelle McDaniel, RN
  • Kerry Mann, RN
  • Kathy Adair, RN
  • Katherine Hagge, RN

##Research team

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Facility Management/Capabilities

  • Outpatient vs Inpatient capabilities
  • Partnering with hospital system
  • Staffing/privileges
  • Clear communication with inpatient team (nurses, pharmacists, APPs, doctors, ER)
  • Inservice for outpatient and inpatient teams (knowledge is power)
  • Joint plan, teamwork
  • Management plan is key—plan for the worst☺

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Management Plans

  • Protocol For Bispecific Antibody Post Treatment Monitoring for CRS/ICANS
    • Ambulatory setting and post hospital discharge monitoring
  • Protocol for Bispecific Antibody Inpatient Management
    • Appropriate order sets made for inpatient mgmt CRS/ICANS
    • Administration
    • Reactions vs CRS
    • Education on management
    • When to call

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Communication

  • Identify Bispecific in EMR
  • SUD info *cycle, day
  • Trial/Commercial
  • Team assigned (A vs B)
  • Monday (weekly) email
  • Documents (CRS, ICANS, Drug)

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What do you do when you start a patient?

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CRS/ICANs Risk Mitigation/Management�(what happens before Toci)

  • Education
  • 1L NS IVF pre and post administration of bispecific
  • Pre medications (Dex steroid of choice)
  • Dexamethsone 4 mg tablets x 4 (16 mg) as “pill in the pocket” for home
  • Tylenol and NSAIDs
  • Drug Bracelet
  • Pocket Cards

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EPCORE NHL-1 Follicular Lymphoma (FL) Cycle (C) 1 Optimization (OPT) Cohort: �Expanding the Clinical Utility of Epcoritamab in Relapsed or Refractory (R/R) FL

Julie M. Vose, MD, MBA,1 Umberto Vitolo, MD,2 Pieternella J. Lugtenburg, MD, PhD,3 Martine E.D. Chamuleau, MD, PhD,4 �Kim M. Linton, MBChB, PhD,5 Catherine Thieblemont, MD, PhD,6 Kristina Sonnevi, MD, PhD,7 Wojciech Jurczak, MD, PhD,8 �Adam J. Olszewski, MD,9 Farrukh Awan, MD,10 Craig Okada, MD, PhD,11 Tatyana Feldman, MD,12 Martin Hutchings, MD, PhD,13 �Elena Favaro, MD, PhD,14 Daniela Hoehn, MD, PhD,15 Zhu Li, MS, PhD,15 Rebekah Conlon, BN,16 Juan-Manuel Sancho, MD, PhD,17 �Julio C. Chavez, MD18

1University of Nebraska Medical Center, Omaha, NE, USA; 2Candiolo Cancer Institute, FPO-IRCCS, Candiolo (Turin), Italy; 3On behalf of the Lunenburg Lymphoma Phase I/II Consortium-HOVON/LLPC, Erasmus MC Cancer Institute, University Medical Center, Department of Hematology, Rotterdam, Netherlands; 4On behalf of the Lunenburg Lymphoma Phase I/II Consortium-HOVON/LLPC, Amsterdam UMC, VU University Medical Center, Amsterdam, Netherlands; 5The Christie NHS Foundation Trust, Manchester Cancer Research Centre, and Division of Cancer Sciences, University of Manchester, Manchester, UK; 6Assistance Publique & Hôpitaux de Paris (APHP), Hôpital Saint-Louis, Hémato-oncologie, Université de Paris, Paris, France; 7Karolinska Institutet, Stockholm, Sweden; 8MSC National Research Institute of Oncology, Kraków, Poland; 9Lifespan Cancer Institute, The Warren Alpert Medical School of Brown University, Providence, RI, USA; 10The University of Texas Southwestern Medical Center, Dallas, TX, USA; 11Oregon Health & Science University Knight Cancer Institute, Portland, OR, USA; 12John Theurer Cancer Center at Hackensack Meridian Health, Hackensack Meridian Health School of Medicine, Hackensack, NJ, USA; 13Rigshospitalet and University of Copenhagen, Copenhagen, Denmark; 14Genmab, Copenhagen, Denmark; 15Genmab, Plainsboro, NJ, USA; 16AbbVie, North Chicago, IL, USA; 17Catalan Institute of Oncology (ICO), ICO Hospital Germans Trias i Pujol, Badalona, Spain; 18Moffitt Cancer Center, Tampa, FL, USA

Presented at the American Society of Clinical Oncology Annual Meeting; May 31–June 4, 2024; Chicago, IL

7015

MED-GL-Epco-0000174

For Reactive Use Only – Not For Distribution

15

ASCO 2024

Epcoritamab in R/R FL

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C1 OPT Substantially Reduced Incidence and Severity of CRS and ICANS

aGraded by Lee et al 2019 criteria.1 bAll grade 1–2; none leading to discontinuation. 1. Lee DW, et al. Biol Blood Marrow Transplant. 2019;25:625-38.

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Pivotal

N=128

C1 OPT

N=86

CRS,a n (%)

85 (66)

42 (49)

Grade 1

51 (40)

34 (40)

Grade 2

32 (25)

8 (9)

Grade 3

2 (2)

0

Treated with tocilizumab, n (%) 

31 (24)

10 (12)

Leading to epcoritamab discontinuation, n (%)

0

0

CRS resolution, n/n (%)

85/85 (100)

42/42 (100)

Median time to resolution, d (range)

2 (1–54)

2 (1–14)

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ICANS, n (%)

8 (6)b

0

  • In C1 OPT, with no mandatory hospitalization, 54% of patients who received the first full dose (44/82) had outpatient monitoring for CRS
    • Regardless of hospitalization status at the first full dose, 77% of patients with CRS following the first full dose (23/30) had CRS onset in the outpatient setting; all were able to identify CRS signs/symptoms in a timely manner and receive adequate treatment
  • In both cohorts, most CRS occurred after the first full dose and was confined to C1; median time to CRS onset after the first full dose was 2.5 days in C1 OPT

Patients (%)

Cycle 1

Patients in C1 OPT With CRS Events �by Dosing Period

For Reactive Use Only – Not For Distribution

16

ASCO 2024

Epcoritamab in R/R FL

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Rifkin, R. ASCO 2024. Abstract #7528

9.0%

10

0

5

10

Yr

ASCO 2024: OPTec: Outpatient Step-Up Administration of Teclistamab in RRMM

  • The MajesTEC-1 study showed that prophylactic tocilizumab (proToci) reduced the incidence and severity of cytokine release syndrome (CRS) associated with Tec.
  • This study aims to evaluate the use of proToci to facilitate safe outpatient administration of the Tec step-up dosing regimen.

Primary Endpoint

Overall incidence of CRS

Secondary Endpoints

Recurrent CRS grade ≥3, infections, neurotoxicity (including ICANS), neutropenia, and efficacy

Eligible Patients

≥18 years, RRMM, ≥4 prior lines of therapy

Exclusions

Rapidly progressing MM, CNS involvement, active infection, contraindication to tocilizumab

Intervention

Tocilizumab 8 mg/kg IV 2-4 hours prior to Tec SUD 1, followed by weekly Tec SUD regimen

Results (Initial Cohort)

10 patients enrolled, median age 74 years, median 4.5 prior therapies

No grade >3 CRS or neurotoxicity/ICANS observed

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CRS Management

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ICE questionnaire

Ask the patient the following questions (1 point per question):

What year is it?

1 point

 

What month is it?

1 point

 

What city are you in?

1 point

 

What street do you live on?

1 point

 

Naming 3 objects (1 point per object)

Hold up 3 separate available objects and see if the patient can easily identify what the objects are

Object 1

1 point

 

Object 2

1 point

 

Object 3

1 point

 

Following simple commands (1 point total):

*Raise your left hand

*Raise your right hand

*Touch your fingertip to your nose

1 point

 

Writing standard sentence

“The sky is blue, and the grass is green”

1 point

 

Attention to count backwards from 100 by 10

1 point

 

Total point score:

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ICANS Management

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Consensus Recommendations on the Management of Toxicity Associated with CD3xCD20 Bispecific Antibody Therapy�

Jennifer L. Crombie1*, Tara Graff2*, Lorenzo Falchi3*, Yasmin Karimi4*, Rajat Bannerji5, Loretta Nastoupil6, Catherine Thieblemont7, Renata Ursu8, Nancy Bartlett9, Victoria Nachar4, Jonathan Weiss4, Jane Osterson2, Krish Patel10, Joshua Brody11, Jeremy S. Abramson12, Matthew Lunning13, Nirav N. Shah14, Ayed Ayed15, Manali Kamdar16, Benjamin Parsons17, Paolo Caimi18, Ian Flinn19, Alex Herrera20, Jeffrey Sharman21, Marshall McKenna5, Philippe Armand1, Brad Kahl9, Sonali Smith22, Andrew Zelenetz3, Elizabeth Budde20*, Martin Hutchings23*, Tycel Philips4*, Michael Dickinson24*

https://doi.org/10.1182/blood.2023022432

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Bispecific Antibody (BsAb) Management in B-cell Lymphomas

  • BsAb represent a novel therapy for B cell Lymphomas and a safe management plan for inpatient and/or outpatient use is essential.
  • Crombie, Graff et al, Blood, DOI, PMID

​

Patient receives BsAb in inpatient/ outpatient setting

Patient or caregiver self-monitor vitals at home during step up dosing

Patient is assessed by HCP at 24 and 48 hours, and as needed post administration

Drug

administration

Self-

Monitoring

(if outpatient)

CRS/Neurotoxicity assessment

with high-risk doses

Patient and caregiver educated on CRS/Neurotoxicity risk and monitoring

Patient Education

Patient assessment is negative for CRS/Neurotoxicity

CRS management

(Table 2)

Neurotoxicity management

(Table 3)

Assessment is positive for CRS and/or Neurotoxicity

Subsequent monitoring repeated as above

Continue therapy and monitoring as directed

  • CRS-risk assessment
  • Tumor burden
  • Co-morbidities
  • Social support

Patient Selection

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Other Considerations

  • Infection prophylaxis
  • IVIG
  • Toci for prophylaxis when appropriate, outpatient setting
  • Educate on nuances

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Commercially Approved BsAb

  • Epcoritamab and Mosunetuzumab (3L FL)
  • Epcoritamab and Glofitamab (3L DLBCL)
  • Teclistamab, Talquetamab and Eltranatamab (MM)
  • Imdeltra (tarlanatamab) ES SCLC
  • Kimmtrak (Tebentafusp) Uveal Melanoma

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Take Home Points

  • More drugs, more patients
  • Nuances to all of these drugs—not all created the same
  • Utilize like mind sites
  • Everyone needs to learn—cannot be a few people
  • Time is now
  • Ask questions, we all learn together

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Communication is key

Education is empowerment

Planning prevents chaos

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Thank you

Questions?

This Photo by Unknown Author is licensed under CC BY