BRIDGE CAR T™

PART 1

PART 2

CAR T-Cell Therapy in NHL:

CAR T-Cell Therapy in NHL:

Coordination of Care Between Our Center and Yours

A Case-Based Workshop

PART

1

CAR T-Cell Therapy in NHL:

Coordination of Care Between Our Center and Yours

Memorial Sloan Kettering Cell Therapy Service • Approximately 8 CAR T-cell therapy infusions for NHL per month • Clinical nurse coordinators: – Dedicated to cellular therapy – Patient’s primary point of contact throughout the CAR T-cell treatment process – Provide comprehensive education to patients and caregivers, coordinate all required pretreatment testing, consultations, appointments, treatment milestones – Identify and address barriers to treatment through collaboration with social work, financial services, and other support resources – Coordinate with manufacturers regarding cell collection, manufacturing updates, product availability, and infusion scheduling – Assess and facilitate readiness for CAR T-cell therapy and assist with regulatory, documentation, and product-specific requirements to ensure timely and safe delivery of therapy – Facilitate handoff to the post-infusion care team following CAR T-cell therapy administration CAR, chimeric antigen receptor; NHL, non-Hodgkin lymphoma.

Memorial Sloan Kettering Cell Therapy Service • CAR T-cell therapy APPs (PAs and NPs) – Inpatient and outpatient APPs: • Inpatient: Collect detailed patient history, order and interpret baseline labs, coordinate administration of CAR T-cell products, monitor patient during and after infusion, oversee supportive care measures, assist with discharge planning, provide discharge education, and arrange outpatient follow-ups • Outpatient: Monitor patients for toxicities, coordinate supportive and logistical care needs, collaborate with multidisciplinary team for ongoing treatment plans, coordinate Day 28+ evaluations, facilitate transition back to primary care team following completion of CAR T-cell treatment

APP, advanced practice provider; NP, nurse practitioner; PA, physician assistant.

Memorial Sloan Kettering Cell Therapy Service • Social workers: – Manage patients receiving cellular therapy – Responsible for psychosocial assessments, housing/lodging, and confirming caregivers

• Case manager for patient financial services (nurse): – Coordinate insurance authorization with payers

• Patient financial navigators: – Available for cellular therapy patients to provide financial guidance

• Team members collaborate with our intake team to screen incoming referrals for possible clinical trials

What Is the Process for CAR T-Cell Therapy?

Chimeric antigen receptor

Collect blood

Isolation and reprogramming of T cells

1

2 T cells

CAR T-cell Therapy Lymphodepletion/ Chemotherapy

5

4

CAR T cells attack cancer cells

Infusion

Uscanga-Palomeque AC, et al. Int J Mol Sci. 2023;24(21):15688.

CAR T cells

3 Multiplication

Lisocabtagene maraleucel (liso-cel) • Indicated for the treatment of adult patients with1: – LBCL, including DLBCL not otherwise specified, high-grade BCL, primary mediastinal LBCL, and FL grade 3B that is relapsed/refractory (R/R) to 1L chemoimmunotherapy, R/R to 1L chemoimmunotherapy in patients not eligible for HSCT due to comorbidities or age, or R/R after ≥2 lines of systemic therapy – R/R CLL or SLL who have received ≥2 lines therapy, including a BTK inhibitor and BCL-2 inhibitora – R/R FL who have received ≥2 prior lines of systemic therapy – R/R MCL after ≥2 lines of systemic therapy, including a BTK inhibitor – R/R MZL after ≥2 lines of systemic therapy

• Administered IV as 1:1 CD8 and CD4 components, supplied in separate vials1

Liso-cel Structure2 Flexible linker

Whitlow

Binding domain (scFv/nanobody) Hinge domain Transmembrane domain Costimulatory domain

IgG4

CD3ζ

CD3ζ

1L, first line; 4-1BB, tumor necrosis factor receptor superfamily member 9; BCL, B-cell lymphoma; BCL-2, B-cell lymphoma 2; BTK, Bruton tyrosine kinase; CLL, chronic lymphocytic leukemia; DLBCL, diffuse large B-cell lymphoma; FL, follicular lymphoma; HSCT, hematopoietic stem cell transplantation; IgG4, immunoglobulin G4; IV, intravenous; LBCL, large B-cell lymphoma; MCL, mantle cell lymphoma; MZL, marginal zone lymphoma; R/R, relapsed/refractory; scFv, single-chain fragment variable; SLL, small lymphocytic leukemia. aApproved under accelerated approval based on response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s).

1. Drugs@FDA. https://www.accessdata.fda.gov/scripts/cder/daf; 2. Bernard G, Evgin L. Front Immunol. 2025;16:1664403.

CD28

4-1BB

Axicabtagene ciloleucel (axi-cel) • The first FDA-approved CAR T-cell therapy for R/R LBCL1 • Now indicated for the treatment of adult patients with2: – LBCL that is R/R to 1L chemoimmunotherapy – R/R LBCL after ≥2 lines of systemic therapy for DLBCL not otherwise specified, primary mediastinal LBCL, high-grade B-cell lymphoma, and DLBCL arising from FL – R/R FL after ≥2 lines of systemic therapya

• Administered IV as a single infusion2

Axi-cel Structure3 Flexible linker

Whitlow

Binding domain (scFv/nanobody) Hinge domain Transmembrane domain Costimulatory domain

CD28

CD3ζ

CD3ζ

FDA, US Food and Drug Administration. aApproved under accelerated approval based on response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s).

1. King AC, et al. J Adv Pract Oncol. 2019;10(8):878-882; 2. Drugs@FDA. https://www.accessdata.fda.gov/scripts/cder/daf/; 3. Bernard G, Evgin L. Front Immunol.

2025;16:1664403.

CD28 CD28

Brexucabtagene autoleucel (brexu-cel) • Indicated for the treatment of adults with1,a: – R/R MCL

• Administered IV as a single infusion1

aAlso FDA-approved for adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL).

1. Drugs@FDA. https://www.accessdata.fda.gov/scripts/cder/daf/; 2. Bernard G, Evgin L. Front Immunol. 2025;16:1664403.

Brexu-cel Structure2 Flexible linker

Whitlow

Binding domain (scFv/nanobody) Hinge domain Transmembrane domain Costimulatory domain

CD28

CD3ζ

CD3ζ

CD28 CD28

Tisagenlecleucel (tisa-cel) • Indicated for the treatment of adults with1,a: – R/R LBCL after ≥2 lines of systemic therapy, including DLBCL not otherwise specified, high-grade BCL, and DLBCL arising from FL – R/R FL after ≥2 lines of systemic therapyb

• Administered IV in 1 to 3 patient-specific infusion bags1

Tisa-cel Structure2 Flexible linker

(G4S)3

Binding domain (scFv/nanobody) Hinge domain Transmembrane domain Costimulatory domain

CD8α

CD3ζ

CD3ζ

aAlso indicated for patients up to 25 years of age with B-cell precursor acute lymphoblastic leukemia (ALL) that s refractory in in second or later relapse; bApproved under

accelerated approval based on response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s).

1. Drugs@FDA. https://www.accessdata.fda.gov/scripts/cder/daf/; 2. Bernard G, Evgin L. Front Immunol. 2025;16:1664403.

CD8α 4-1BB

CAR T-Cell Therapy Recommendations for NHLs NCCN Recommendations

FL1

MZL1

MCL1

DLBCL1

CLL/SLL2

CD19-directed CAR Tcell therapy as a preferred option in 3L and as subsequent therapy: •Lisocabtagene maraleucel •Axicabtagene ciloleucel •Tisagenlecleucel

CD19-directed CAR Tcell therapy in 3L and as subsequent therapya: •Lisocabtagene maraleucel (preferred) •Axicabtagene ciloleucelb (other recommended)

CD19-directed CAR Tcell therapy in 2L or as subsequent therapy in patients with progressive disease after prior covalent BTKi (useful in certain circumstances): •Lisocabtagene maraleucel •Brexucabtagene autoleucel

CD19-directed CAR T-cell therapy in 2L in relapsed disease (<12 months or primary refractory disease) who are candidates for CAR T-cell therapy: •Lisocabtagene maraleucel (Category 1) •Axicabtagene ciloleucel (Category 1)

CD19-directed CAR Tcell therapy as a preferred therapy option for R/R disease after prior cBTKibased and BCL2icontaining regimens: •Lisocabtagene maraleucel ± ibrutinib

CD19-directed CAR T-cell therapy as a preferred option in 2L in patients with relapsed disease (>12 months) and no intention to proceed to transplant: •Lisocabtagene maraleucel (with pre/postpheresis as needed; if eligible) CD19-Directed CAR T-cell therapy as a preferred therapy option in 3L and as subsequent therapy: •Lisocabtagene maraleucel •Axicabtagene ciloleucel •Tisagenlecleucel

2L, second line; 3L, third line; BCL2i, B-cell lymphoma 2 inhibitor; cBTKi, covalent Bruton tyrosine kinase inhibitor; NCCN, National Comprehensive Cancer Network. a2L therapy regimens that were not previously given can also be used as options for 3L and subsequent therapies 1; bAlthough recommended by the NCCN, axi-cel is not currently approved for use in MZL at this time.1,3 1. NCCN. NCCN Guidelines Version 4.2026. B-Cell Lymphomas. https://www.nccn.org/professionals/physician_gls/pdf/b-cell.pdf; 2. NCCN. NCCN Guidelines Version 2.2026. Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma. https://www.nccn.org/professionals/physician_gls/pdf/cll.pdf; 3. Drugs@FDA. https://www.accessdata.fda.gov/scripts/cder/daf/.

Key Patient and Disease Factors in Determining Candidacy for CAR T-Cell Therapy Indications1 Kinetics of Disease Progression1

Immediate Prior Therapy1 Concomitant Immunosuppressive Therapy1 Active Infection2 Non–Disease-Related Comorbidities1

• Does the patient have a disease and therapy history that meets the FDA label?

• Does the patient meet the criteria for a clinical trial?

• Can the patient tolerate leukapheresis (without immediate use of steroids/chemotherapy) and remain stable until the T-cell infusion (3-4 weeks)?

• Does the patient need alternative therapy prior to CAR T-cell therapy consideration?

• How might it affect the ability to successfully manufacture CAR T cells (ie, obtain sufficient number of T cells and expand)?

• Can this be safely stopped prior to T-cell collection?

• Higher risk of complications if patient experiences CRS • Does the patient have organ function reserve to tolerate toxicities of CAR T-cell therapy, namely CRS and ICANS • Cardiac, pulmonary, renal, bone marrow, CNS

CNS, central nervous system; CRS, cytokine release syndrome; ICANS, immune effector cell-associated neurotoxicity syndrome.

1. Hayden P, et al. Ann Oncol. 2022;33(3):259-275; 2. Amini L, et al. Nat Rev Clin Oncol. 2022;19(5):342-355.

Considerations When Determining Patient Eligibility for CAR T-Cell Therapy Patient Characteristic Advanced age

Expert Recommendations Surrounding CAR T-Cell Eligibility • Age by itself should not be a reason to exclude patients from CAR T therapy referral, and should be considered along with other factors • Patients of advanced age should be referred for further assessment

Poor performance status

• Patients should be referred for further assessment, even with marginal performance status

Lack of response to chemotherapy

• Chemosensitivity is not required before CAR T therapy referral • Consult with a CAR T therapy specialist when choosing bridging therapy for disease control

Impaired cardiovascular function

• Individual cardiac markers do not disqualify patients from CAR T therapy referral • Cardiologists or oncocardiologists should be involved early in patient care to optimize cardiac status

Impaired pulmonary function

• Pulmonary function tests are not universally required as part of assessment for CAR T eligibility • In patients with concerning pulmonary conditions or history, early consultation with pulmonologists is critical

Impaired renal function

• CAR T therapy could be considered in selected patients with significant renal dysfunction

Impaired hepatic function

• Refer and consult hepatologists and/or gastrointestinal specialists

Unresolved, active, or chronic infections Poor psychological health Social support Other considerations

• Refer and consult infectious disease specialists • Special considerations may be given to patients with aggressive disease or poor prognosis to receive CAR T therapy despite active infections

• Refer and solicit support from psychiatric unit • Caregiver support is critical, especially during the 2-week monitoring period • Factors that should not restrict patients for CAR T-cell referral include autoimmune disease, obesity, history of solid organ transplantation, and sCNS involvement

sCNS, secondary central nervous system.

Shadman M, et al. Transplant Cell Ther. 2026;32(3):277-287.

Key Differences and Considerations Between CAR T-Cell Therapies and Bispecific Antibodies Feature

CAR T-Cell Therapy

BsAbs

Therapy type1

Autologous cellular therapy

“Off-the-shelf” recombinant proteins

Manufacturing time1

Several weeks (patient-specific)

Immediate availability

Administration1,2

Single infusion; in-patient setting

Multiple doses; often outpatient/subcutaneous

T-cell persistence1

Long-lived memory T cells

Shorter half-life; persistence depends on dosing

Safety profile1,2

High risk of CRS and neurotoxicity (ICANS)

Generally milder CRS and fewer neurotoxic events

Toxicity management1

Require specialized centers and intensive monitoring

Step-up dosing mitigates CRS risk

Cost and accessibility 1,2

Higher upfront costs; limited to specialized centers

Lower upfront costs; more accessible

Treatment setting1

Proximity to treatment centers needed due to complexity and side effects

Potential for outpatient administration

Long-term outcomes 2

Potential long-term remission

Still under study

BsAb, bispecific antibody.

1. Abou DS, et al. Cancer Med. 2026;15(2):e71562; 2. Morabito F, et al. Eur J Haematol. 2025;114(1):4-16.

Effective Partnership Between Community Oncologists and CAR T-Cell Treatment Centers First relapse

Leukapheresis

Bridging therapy

Infusion

Return to the community

Long-term follow-up

Z

• Early interaction with treatment center to refer to CAR T-cell therapy at appropriate line • Understand eligibility criteria to obtain early referrals • Direct line of communication with treatment center physicians

• Early, direct communication with leukapheresis center to optimize manufacturing process • Understand negative effects of bendamustine and other therapies on T-cell fitness • Collaborate with leukapheresis center throughout the process

Hoffman MS, et al. Transplant Cell Ther. 2023;29(7):440-448.

• Understand appropriate bridging therapy options to maintain disease control and ensure CAR T-cell therapy eligibility

• Stay aware of the infusion process and state of the patient following infusion

• Ensure you have received clear, direct instructions in handoff for follow-up care

• Understand signs to monitor to identify early relapses; follow imaging protocols • Follow up long term for management of cytopenias and B-cell aplasia and monitor for rare late relapses • Monitor for long-term immune reconstitution

Types of Therapies Used Before CAR T-Cell Therapy Holding Therapy

• Treatment patient is on when they are referred for CAR T-cell therapy Holding Therapy (Prepheresis) Options Include DHA + platinum therapy ± rituximab

Gemcitabine/dexamethasone/carboplatin or cisplatin ± rituximab GEMOX ± rituximab Ifosfamide/carboplatin/etoposide ± rituximab Polatuzumab vedotin ± rituximab ISRT (as monotherapy or sequentially with systemic therapy) PLEASE NOTE: Patients who will be receiving treatment with CAR T-cell therapy or bsAbs should not be treated with bendamustine prior to leukapheresis; bendamustine use should be delayed until after CAR T leukapheresis DHA, dexamethasone/cytarabine; GEMOX, gemcitabine hydrochloride and oxaliplatin; ISRT, involved site radiation therapy.

NCCN. NCCN Guidelines Version 4.2026. B-Cell Lymphomas. https://www.nccn.org/professionals/physician_gls/pdf/b-cell.pdf.

Types of Therapies Used Before CAR T-Cell Therapy Bridging Therapy

• Treatment given while awaiting manufacture of the CAR T cells

Examples of Bridging Therapies ≥1 Cycles as Needed Until CAR T-Cell Product Is Available DHA + platinum therapy ± rituximab Gemcitabine/dexamethasone/carboplatin or cisplatin ± rituximab GEMOX ± rituximab Ifosfamide/carboplatin/etoposide ± rituximab Polatuzumab vedotin ± rituximab ± bendamustine ISRT (as monotherapy or sequentially with systemic therapy)

NCCN. NCCN Guidelines Version 4.2026. B-Cell Lymphomas. https://www.nccn.org/professionals/physician_gls/pdf/b-cell.pdf.

Plans for Managing Disease Symptoms During Bridging Therapy APPs should follow up regularly with patients and monitor their LDH and CRP levels, assess for lymphadenopathy, and assess functional status APPs and nurse coordinators should be aware of all possible bridging therapy regimens and their potential associated toxicities, as well as the supportive care needed for radiation and immunotherapy Multidisciplinary care teams should understand the follow-up recommendations for evaluating blood counts, palpable lymphadenopathy, and infection risk It is critical to maintain close communication between the CAR T therapy center physicians and the referring physician, as bridging therapy may need to be administered at either location CRP, C-reactive protein; LDH, lactate dehydrogenase.

Beaupierre A, et al. J Adv Pract Oncol. 2019;10(suppl 3):29-40.

Types of Therapy Used Before CAR T-Cell Therapy Lymphodepletion

• Treatment that induces immunosuppression to aid in CAR T-cell engraftment, expansion, and persistence, in order to help improve patient outcomes – Given before CAR T cells are infused – Fludarabine + cyclophosphamide is most commonly used but bendamustine has also been demonstrated to be a viable alternative

Canelo-Vilaseca M, et al. Bone Marrow Transplant. 2025;60(5):559-567.

Patient-Related Barriers to CAR T-Cell Therapy Barriers1 Long distance to CAR T-cell therapy center and relocation required

• Treatment cost

Access to a 24/7 caregiver to observe for TEAEs

• Costs not covered by insurance (food, gas, lodging)

Concern about loss of caregiver income during relocation

Fear of severe TEAEs and hospitalization

Financial toxicity: • Lack of insurance coverage

Solutions1 Financial assistance for relocation, transportation; caregiver support resources

Example of free lodging for patients with cancer and caregivers relocating for treatment in New York, New York2

Patient education about what to expect for TEAEs and risk of CRS, ICANS Early transition back to the community

Change in REMS requirement (more on this later)

REMS, Risk Evaluation and Mitigation Strategies; TEAE, treatment-emergent adverse event.

1. Hoffman MS, et al. Transplant Cell Ther. 2023;29(7):440-448; 2. American Cancer Society. https://www.cancer.org/support-programs-and-services/patient-lodging/hopelodge/new-york-city.html.

Clinician-Related Barriers to Referral for CAR T-Cell Therapy Long distance to CAR T-cell therapy center and relocation required Lack of awareness of CAR T-cell therapy for earlier-line treatment Late referral to CAR T-cell therapy Lack of understanding of AE management AE, adverse event.

Hoffman MS, et al. Transplant Cell Ther. 2023;29(7):440-448.

Expansion of CAR T-cell therapy for other cancers (and potentially for autoimmune diseases in future) causing increased volume of patients and decreased number of leukapheresis slots Lack of knowledge about CAR T-cell therapy safety and efficacy

Lack of knowledge about negative effect some therapies can have on T-cell fitness Lack of knowledge of eligibility criteria

Importance of Early Communication With the CAR T-Cell Treatment Center Team Before initial consultation at a CAR T therapy center, APPs and the referring physician should work together to assure the patient meets the requirements to be considered an appropriate candidate for CAR T-cell therapy

APPs, the treating physician, and nurse coordinator at the CAR T treatment center should communicate with the referring physician about patient eligibility for treatment, treatment timelines, and plans for chemotherapy prior to CAR T-cell therapy infusion Close communication between APPs, nurse coordinators, and the referring physician is critical during leukapheresis, when the patent must follow specific protocols for chemotherapy and steroid treatment

Continued communication between the referring physician and CAR T treatment center is essential, since the referring physician will continue to be involved in the patient’s CAR T therapy journey Beaupierre A, et al. J Adv Pract Oncol. 2019;10(suppl 3):29-40.

Resources to Help Patients Undergoing CAR T-Cell Therapy • Insurance and financial assistance – Social workers and patient financial navigators provide available financial resources

– Dedicated case managers for patient financial services provide insurance authorization coordination

• Caregiver support – Caregiver resource library: educational materials, dedicated video for caregivers – Formalized Caregiver Clinic through Memorial Sloan Kettering (MSK) (https://www.mskcc.org/experience/caregivers-support)

• Addressing socioeconomic barriers – Social workers and patient financial navigators provide screening and interventions with available financial, travel, and meal support

• Lodging and transportation – Dedicated residence for cellular therapy patients (75th Street Housing) – Travel vouchers available for some patient travel support – MSK-arranged discounted hotel partnerships for patients and caregivers

• Community transportation resources (air travel assistance) – Transportation resources are available through manufacturer-supported programs

• Ground transportation – Shuttle available through MSK (https://www.mskcc.org/locations/planning-visit-travel-tomsk/patient-shuttle)

• MSK Patient Travel Program – Programs available through MSK

Patient Education Resources Patient Advocacy Group Resources • Cancer Support Community – https://www.cancersupportcommunity.org/car-tcell-therapy

• Blood & Marrow Transplant Information Network – https://bmtinfonet.org/transplant-article/rolecaregiver-and-car-t

• Blood Cancer United – https://bloodcancerunited.org/resources/patients

MSK Patient Resources • Caregiver support groups and formalized Caregiver Clinic – https://www.mskcc.org/experience/caregiverssupport

• Dedicated CAR T patient education materials • 1:1 dedicated CAR T patient education sessions • 24/7 access to oncology-dedicated urgent care center to manage adverse events • MSK’s CAR T Patient Values/Goals of Care and Survivorship Program

CAR T-Cell Toxicities and Timing After Treatment Initiation Lymphodepleting chemotherapy

Neutropenia

Cyclophosphamide Fludarabine

Steroids, anti–IL-6

CRS, ICANS

B-cell aplasia, hypogammaglobulinemia, specific Ab deficiency

Endothelial, mucosal damage

Delayed cytopenias

*ICU, invasive measures

… Day -5

0

7

14

21

30

60

90

180

365

Patients treated with CAR-T cell therapy at MSK are discharged to community oncologist care after approximately 100 days (3 months).

Ab, antibody; ICU, intensive care unit; IL-6, interleukin 6.

Image adapted from Kampouri E, et al. Transpl Infect Dis. 2023;25(suppl 1):e14157.

Predictors of High-Grade CRS and ICANS PRETREATMENT1-3

POSTTREATMENT1-3

• Poor performance status

• CAR T-cell construct used

• Elevated baseline levels of IL-6 and ferritin

• No bridging therapy, or stable or progressive disease after bridging therapy

• Higher baseline macrophage scores and activated M1 and M2 macrophages

• Low platelet levels (<150 g/L) • Elevated CRP levels (>30 mg/L) • Presence of bulky disease/high tumor burden

• Fever that develops within 24 hours of CAR T-cell infusion • Elevated peak levels of serum IL-6, IFN-γ,TNFα, and IL-15

• Elevated LDH level (>2 times the upper limit of normal) IFN, interferon; TNF, tumor necrosis factor.

1. Faramand R, et al. Clin Cancer Res. 2020;26(18):4823-4831; 2. Sesques P, et al. J Hematol Oncol. 2024;17(1):61; 3. Goto H. J Clin Exp Hematop. 2025;65(4):268-275.

Long-Term AEs After CAR T-Cell Infusions Late Complications and Long-Term Care of Adult CAR T-Cell Patients Long-term survivors of CAR T-cell therapy are at risk for unique long-term complications CAR T cell

Target antigen

LATE CYTOPENIAS

• May be ongoing cytopenias from early toxicity • May arise anew, raising concerns for recurrent disease or secondary malignancy

LATE INFECTIONS

• Result of persistent T- and B-cell lymphomas • Tend to be predominantly viral infections • Acyclovir prophylaxis recommended for all patients

HYPOGAMMAGLOBULINEMIA

• Direct effects of lymphodepleting chemotherapy and CAR T cells on B cells and plasma cells • Immunoglobulin replacement therapy generally not recommended unless recurrent infections

SECONDARY MALIGNANCIES

• Ongoing 5% to 10% lifetime risk of a secondary hematologic or solid malignancy • Risk of CAR-inducted T-cell secondary cancer <1%

LATE NEUROLOGIC TOXICITIES

• Early neurocognitive deficits may persist but generally resolve within 12 months • Late-onset neurologic toxicities distinct from ICANS and associated anti-BCMA CAR T cells

BCMA, B cell maturation antigen.

Image adapted from Bishop MR. Hematology Am Soc Hematol Educ Program. 2024;(1):109-115.

Monitoring and treatment is a joint collaboration between the CAR T-cell center and the community hematologistoncologist

Predictors of High-Grade B-Cell Aplasia, Hypogammaglobulinemia, and Cytopenias PRETREATMENT

POSTTREATMENT

• Infection

• CRS (grade ≥4 is a risk factor for late cytopenias)

• Higher baseline ferritin and CRP

• ICANS (grade ≥3 is a risk factor for late cytopenias)

• Prior HSCT within the previous year

• IEC-HS

• Prior radiotherapy

• Bone marrow destruction and inadequate immune reconstitution

• Baseline tumor burden • Low baseline hematopoietic reserves • History of ≥3 prior lines of chemotherapy

• Low CD4+/CD8+ T-cell ratio of CAR T cells • Severe hematologic toxicity after lymphodepletion • Expansion of CAR T cells • Type of CAR construct

IEC-HS, immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome.

Yang Y, et al. Exp Hematol Oncol. 2024;13(1):110.

REMS Elimination and New Workflow for Early Release After CAR T-Cell Therapy June 27, 2025 • Breyanzi (lisocabtagene maraleucel)

• Kymriah (tisagenlecleucel) • Tecartus (brexucabtagene autoleucel) • Yescarta (axicabtagene ciloleucel) • Abecma (idecabtagene vicleucel)

• Carvykti (ciltacabtagene autoleucel)

FDA.gov. https://www.fda.gov/news-events/press-announcements/fda-eliminates-risk-evaluation-and-mitigation-strategies-rems-autologous-chimeric-antigen-receptor.

Changes Due to REMS Elimination • Hospitals and their associated clinics dispensing these therapies are no longer required to be specially certified or to maintain on-site, immediate access to tocilizumab1,2 • Update requiring monitoring of patients for at least 2 weeks, including daily monitoring for at least 1 week2 • Patients now must remain near their CAR T-cell center for at least 2 weeks2 • Patients must be advised to avoid driving for 2 weeks following CAR T-cell administration2 1. FDA.gov. https://www.fda.gov/news-events/press-announcements/fda-eliminates-risk-evaluation-and-mitigation-strategies-rems-autologous-chimeric-antigen-receptor; 2. FDA.gov. https://www.fda.gov/vaccines-blood-biologics/safety-availability-biologics/fda-eliminates-risk-evaluation-and-mitigation-strategies-rems-autologous-chimericantigen-receptor.

Long-Term Monitoring Weeks to Months After Infusion ONGOING MONITORING

PROPHYLAXIS

VACCINATION

• Consider targeted monitoring for CMV, EBV, and HHV-6 for specific patient populations • Monitor chronic HBV carriers with monthly liver enzymes and HBV DNA tests to detect early reactivation • Perform regular physicals to ensure patients do not have active infections

• Prophylaxis with fluoroquinolone may be considered during the expected period of neutropenia, until ANC recovery • Antiviral prophylaxis for HSV, VZV, and HBV – In a patient with a rising CMV viral load, infectious disease consultation should be requested for further management • Antifungal prophylaxis for Pneumocysitis jirovecii

• Patients should only receive seasonal vaccination for influenza and SARS-CoV-2 prior to CAR T-cell therapy • ≥3 months after CAR T-cell therapy, patients can be (re)vaccinated for influenza, RSV, and SARS-CoV-2 • Beginning ≥6 months after CAR T-cell treatment, patients should be (re)vaccinated for the following: – Streptococcus pneumoniae – HAV – HBV – Clostridium tetani – Cornybacterium diphtheriae – Bordetella pertussis – VZVa (for seropositive adults or patients with a history of chickenpox or shingles)

ANC, absolute neutrophil count; CMV, cytomegalovirus; EBV, Epstein Barr virus; GVHD, graft-versus-host disease; HAV, hepatitis A virus; HBV, hepatitis B virus; HHV-6, human herpesvirus 6; HSV, herpes simplex virus; RSV, respiratory syncytial virus; VZV, varicella zoster virus. aNot until ≥1 year post CAR T-cell therapy, ≥1 year post transplant, ≥8 months off of all systemic immunosuppressive therapy for GVHD, and absolute CD4 T cell count >200 cells/µL. Shahid Z, et al. Transplant Cell Ther. 2024;30(10):955-969.

Overview of Assessments Performed Before, During, and After CAR T-Cell Treatment Before Treatment • Detailed health history • Baseline performance status • Organ function • Baseline laboratory studies

During Treatment

• Vitals • Infusion-related reactions

After Treatment • Monitoring for post-infusion CRS and ICANS • Monitoring/management of cytopenias • Monitoring for infections • Symptom monitoring • Monitoring for secondary malignancy • Bone marrow biopsies for patients with cytopenia beyond 100 days

CAR T outpatient APP will prepare, order, and coordinate Day 28+ evaluations, which include: • Laboratory studies • Bone marrow biopsies

• CT, PET/CT, or MRI imaging as indicated • Protocol- or disease-specific testing

CT, computed tomography; MRI, magnetic resonance imaging; PET, positron emission tomography.

Information to Be Communicated Between the Treatment Center and Referring Physician The treating physician should provide the patient’s community oncologist with the following information: ❑ Baseline workup results prior to CAR T-cell therapy ❑ The patient’s last progress note from the treatment center, with risks for any prolonged cytopenias and recommended treatments noted ❑ The patient’s latest restaging information ❑ Any laboratory requests, with specific orders, including how often they should be drawn ❑ Guidelines and recommendations for possible blood product administration, if needed ❑ Medication lists (including any prophylactic antibiotics or antiviral medications) ❑ CAR T-cell medication guide ❑ Copy of the patient’s wallet card ❑ An approximate outline of when the patient will need to follow up with the treatment center Beaupierre A, et al. Clin J Oncol Nurs. 2019;23(2):27-34

Managing Adverse Events in Community Practice Once discharged to their referring physician after completing CAR T-cell therapy: • Patients should receive regular, lifelong, local monitoring to ensure they do not develop secondary malignancies following CAR T-cell therapy • Patients should be educated about the risk of infections due to prolonged cytopenias and B-cell aplasia, and should be educated on effective hygiene and infectionprevention strategies • Patients should also be educated on monitoring for signs of relapse, which can include: – Fevers – Night sweats – Palpable lymphadenopathy

Beaupierre A, et al. J Adv Pract Oncol. 2019;10(suppl 3):29-40.

MSK Cellular Therapy Service Contacts • MSK Cellular Therapy Service main phone number: 1-888-MSK-CART (1-888-675-2278) • Referring provider team: https://www.mskcc.org/cancer-care/diagnosis-treatment/cancertreatments/immunotherapy/car-cell-therapy • Email: – New domestic patients, inquiries can be sent to: referapatient@mskcc.org – For international patients, please email: international@mskcc.org

• Phone: – For clinicians (available 24/7): 646-677-7440 – For self-referral: 646-926-0946

• Fax: 646-227-2476 • Self-referral link for patients: https://www.mskcc.org/experience/become-patient/appointment • Additional links: – https://www.mskcc.org/departments/division-hematologic-malignancies/cellular-therapeutics

– https://www.mskcc.org/research-areas/topics/cell-based-therapy

• Hours: – David H. Koch Center: Monday-Friday, 8 AM-6 PM – Memorial Hospital: 24 hours/day, 7 days/week

In summary…

• Early communication with CAR T-cell treatment centers is important for ensuring appropriate patient care1,2 • Many barriers exist that may impede patients’ ability to receive CAR T-cell therapy; however, resources are available to help your patients and their caregivers receive the treatment patients need1 • Toxicities and TEAEs: – Late toxicity looks different than early toxicity 3,4 – Identification of pre- and posttreatment factors that may increase a patient’s risk of developing AEs is key in monitoring patients appropriately5-7

• Ongoing communication between CAR T-cell centers and referring physicians is essential to ensure a smooth transition of patients back to community care following CAR T-cell therapy2 1. Hoffman MS, et al. Transplant Cell Ther. 2023;29(7):440-448; 2. Beaupierre A, et al. J Adv Pract Oncol. 2019;10(suppl 3):29-40; 3. Adkins S. J Adv Pract Oncol.

2019;10(suppl 3):21-28; 4. Bishop MR. Hematology Am Soc Hematol Educ Program. 2024;2024(1):109-115; 5. Yang Y, et al. Exp Hematol Oncol. 2024;13(1):110; 6. Rubin D, et al. JAMA Neurol. 2020;77(12):1536-1542; 7. Rajeski K, et al. Blood. 2023;142(10):865-877.