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3337 Predictors and Characterization of Cytokine Release Syndrome (CRS) and Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) in Patients with Multiple Myeloma Receiving Teclistamab

Program: Oral and Poster Abstracts
Session: 653. Multiple Myeloma: Clinical and Epidemiological: Poster II
Hematology Disease Topics & Pathways:
Research, Bispecific Antibody Therapy, Clinical Research, Plasma Cell Disorders, Diseases, Real-world evidence, Treatment Considerations, Biological therapies, Lymphoid Malignancies
Sunday, December 8, 2024, 6:00 PM-8:00 PM

Oren Pasvolsky, MD1, Aimaz Afrough2*, Lei Feng, MS3*, Wenli Dong3*, Tiffany Richards, PhD, NP4, James A Davis, PharmD5*, Danai Dima, MD6, Ariel Grajales-Cruz7*, Mariola A Vazquez-Martinez, MD7, Aishwarya Sannareddy, MBBS2*, Utkarsh Goel, MBBS8, Rahul Banerjee, MD, FACP9, Mahmoud R. Gaballa, MD4, Alex Lieberman-Cribbin10*, Masooma S Rana, MBBS11*, Kelley Julian, PharmD12*, Christopher J Ferreri, MD13*, Leyla O. Shune, MD14, Shaun DeJarnette14*, Evguenia Ouchveridze, MD15, Sandra Susanibar-Adaniya, MD16, Andrew J. Portuguese17, Peter A. Forsberg, MD18, Hitomi Hosoya, MD, PhD19, Lekha Mikkilineni, MD, MA19, Gurbakhash Kaur, MD, MA20, Adriana Rossi, MD, MSc10, Megan M Herr, PhD21, Erin Eberwein, PharmD22*, Chenyu Lin, MD22, Brandon Blue23, Shahzad Raza, MD6, Yi Lin, MD, PhD24, Joseph P. McGuirk, DO25, Shebli Atrash, MD26, Douglas W Sborov, MD27, Peter M. Voorhees, MD28, Faiz Anwer, MD6, Doris K. Hansen, MD29*, Krina K. Patel, MD, MSc30, Surbhi Sidana, MD31, Andrew J. Cowan, MD32*, Larry D Anderson Jr., MD, PhD33, Shambavi Richard, MD10, Alfred L. Garfall, MD34, Hans C. Lee, MD35 and Jack Khouri, MD6

1Department of Lymphoma & Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX
2UT Southwestern Simmons Cancer Center, Dallas, TX
3Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX
4The University of Texas MD Anderson Cancer Center, Houston, TX
5Division of Hematology-Oncology, Medical University of South Carolina, Charleston, SC
6Department of Hematology and Medical Oncology, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH
7H Lee Moffitt Cancer Center and Research Institute, Tampa, FL
8Department of Hematology and Medical Oncology, Cleveland Clinic, Cleveland, OH
9University of Washington, Seattle, WA
10Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY
11Division of Blood and Marrow Transplantation and Cellular Therapy, Stanford University, Santa Clara, CA
12University of Utah Huntsman Cancer Institute, Salt Lake City, UT
13Department of Hematologic Oncology and Blood Disorders, Atrium Health Levine Cancer Institute, Charlotte, NC
14University of Kansas Medical Center, Kansas City, KS
15Division of Hematologic Malignancies & Cellular Therapeutics, University of Kansas Medical Center, Westwood, KS
16Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA
17Fred Hutchinson Cancer Center, Seattle, WA
18University of Colorado Cancer Center, Denver, CO
19Division of Blood and Marrow Transplantation and Cellular Therapy, Stanford University School of Medicine, Palo Alto, CA
20Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX
21Roswell Park Comprehensive Cancer Center, Buffalo, NY
22Duke University Cancer Institute, Durham, NC
23H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL
24Division of Hematology, Mayo Clinic, Rochester, MN
25Division of Hematologic Malignancies & Cellular Therapeutics, University of Kansas Medical Ctr., Westwood, KS
26Levine Cancer Institute, Charlotte, NC
27Huntsman Cancer Institute, University of Utah, Salt Lake City, UT
28Plasma Cell Disorders Section, Department of Hematologic Oncology & Blood Disorders, Levine Cancer Center, Charlotte, NC
29Moffitt Cancer Center, Tampa, FL
30M.D. Anderson Cancer Center, MD Anderson Cancer Center, Houston, TX
31Division of Blood and Marrow Transplantation and Cellular Therapy, Stanford University School of Medicine, Stanford, CA
32University of Washington Fred Hutchinson Cancer Center, Seattle, WA
33Harold C. Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, TX
34Division of Hematology/Oncology, Hospital of the University of Pennsylvania, Philadelphia, PA
35Department of Lymphoma & Myeloma, MD Anderson Cancer Center, Houston, TX

Background: Teclistamab (Tec) received regulatory approval for the treatment of relapsed refractory multiple myeloma (RRMM) based on the MajesTEC-1 study. The risk of CRS and ICANS with Tec is well established with a manufacturer’s recommendation of inpatient observation for 48-hours for CRS/ICANS monitoring after the initial 3 step up doses. There are limited real-world data on the characteristics of and risk factors for CRS and ICANS with Tec. Such data could inform management of Tec patients (pts), including patient selection for inpatient or outpatient step-up dosing.

Methods: RRMM pts treated with standard-of-care Tec across 13 U.S. academic institutions were included in this analysis. The follow-up data cutoff was 30 April 2024. CRS and ICANS classification was based on the American Society for Transplantation and Cellular Therapy consensus grading criteria. Multivariable logistic regression models were fitted to estimate the effects of covariates on CRS and ICANS events, with a particular focus on grade ≥2 CRS, any-grade ICANS, and the combination of CRS grade ≥2 and/or any-grade ICANS.

Results: 385 pts were included in the analysis, with a median of 6 lines of prior therapy. Median age was 68 years (range 31-92), 88 patients (25% of pts with available data) had ECOG ≥2, and 301 pts (78%) would have been ineligible for MajesTEC-1. 48 (33%) of 145 evaluable pts with a baseline bone marrow (BM) prior to Tec had >50% BM plasma cells, 139 pts (36%) had extramedullary disease (EMD) (either paraskeletal or true-EMD) and 5 pts (1%) had plasma cell leukemia prior to start of Tec. 224 pts (59%) received Tec with an accelerated step-up dosing regimen, defined as having at least one step-up dose interval of ≥ 2 days.

220 pts (57%) developed any-grade CRS [Grade 1: 46% (N=179), grade 2: 10% (N=37), grade 3: 0.8% (N=3), grade 4: 0.3% (N=1)]. Median time to CRS from start of Tec was 3 days (range, 0-15). Fifty-four pts (14%) developed any-grade ICANS [Grade 1: 7% (N=26), Grade 2: 5% (N=18), grade 3: 3% (N=10), grade 4: none]. There were no grade 5 CRS or ICANS events. Median time to onset of ICANS from start of Tec was 4 days (range, 0-25). There was one case of hemophagocytic lymphohistiocytosis in the entire cohort. 38% of pts received tocilizumab and 17% of pts received corticosteroids.

In univariate analysis (UVA), baseline platelet <50, triple-class refractory, penta-refractory status, and EMD prior to start of Tec were associated with increased risk for CRS grade ≥2 (p-values <0.1) and incorporated in MVA.

Baseline platelet <50, age >60, ECOG ≥2, Hgb <8 g/dL, BM plasma cells >50%, and ferritin or CRP in the upper quartile were associated with increased risk for any-grade ICANS in UVA (p-values <0.1).

Baseline platelet <50, ECOG ≥2, Hgb <8 g/dL, BM plasma cells >50%, ferritin or CRP in the upper quartile, and prior BCMA exposure were associated with increased risk of CRS grade ≥2 and/or any-grade ICANS in UVA (p-values <0.1).

Accelerated step-up dosing, renal impairment (CrCl < 30 mL/min) and baseline LDH in the upper quartile were not associated with an increased risk of either CRS or ICANS in UVA.

Baseline BM plasma cells >50% was excluded from multivariable analysis (MVA) due to high number of missing data, since most pts (62%) did not undergo BM biopsy prior to start of Tec.

In MVA, risk factors for CRS grade ≥2 included baseline platelet <50 at the start of Tec treatment (OR: 2.35, 95% CI 1.08-5.08; p=0.03) and penta-refractory disease (OR: 2.48, 95% CI 1.13-5.45; p=0.02). Risk factors for any-grade ICANS included platelet <50 (OR: 4.18, 95% CI 1.88-9.28; p=0.0004), age >60 (OR: 7.54, 95% CI 1.63-34.89; p=0.01) and CRP in the upper quartile (OR: 2.51, 95% CI 1.16-5.43; p=0.02). Risk factors for CRS grade ≥2 and/or any-grade ICANS included platelet <50 (OR: 2.65, 95% CI 1.42-4.94; p=0.002) and ECOG ≥2 (OR: 2.07, 95% CI 1.19-3.61; p=0.01).

Conclusions: This real-world analysis of RRMM pts treated with Tec revealed comparable rates CRS and ICANS relative to the MajesTEC-1 study, and these were mostly limited to grade 1/2. MVA demonstrated a significantly higher risk of CRS grade ≥2 and/or any-grade ICANS in pts with baseline platelet <50 and/or ECOG ≥2, the former may reflect BM disease burden. These results may help identify pts who are at higher risk for IEC related toxicities with Tec that would warrant inpatient monitoring during initial step-up dosing.

OP, AA, & LF: co-first authors. AG, HCL & JK: co-senior authors

Disclosures: Afrough: AbbVie: Research Funding; Adaptive Biotechnology: Research Funding; K36 Therapeutics: Research Funding; Janssen: Research Funding; Karyopharm: Honoraria, Other: Data Safety Monitoring/Advisory Board; Bristol-Myers Squibb: Honoraria, Other: Data safety monitoring/advisory board; Sanofi: Honoraria, Other: Data safety monitoring/advisory board. Davis: Janssen Biotech: Speakers Bureau. Grajales-Cruz: Cellectar Biosciences: Honoraria, Other: Data Safety Monitoring/Advisory Board, Research Funding; Janssen: Honoraria, Other: Data Safety Monitoring/Advisory Board; Sanofi: Honoraria, Other: Data Safety Monitoring/Advisory Board; Amgen: Honoraria; Pfizer: Honoraria, Other: Data Safety Monitoring/Advisory Board. Banerjee: Abbvie; JNJ; Novartis; Pack Health; Prothena; Sanofi: Research Funding; Adaptive; BMS; Caribou Biosciences; Genentech; GSK; JNJ / Janssen; Karyopharm; Legend Biotech; Pfizer; Sanofi; SparkCures: Consultancy. Gaballa: GLG: Consultancy; Guidepoint: Consultancy; Boxer Capital, LLC: Consultancy; Bristol Myers Squibb: Consultancy. Julian: Pfizer: Membership on an entity's Board of Directors or advisory committees; BioLine Rx: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees. Ferreri: Affimed Therapeutics: Current equity holder in private company; Janssen: Consultancy. Shune: BMS: Membership on an entity's Board of Directors or advisory committees; Norvatis: Membership on an entity's Board of Directors or advisory committees; Johnson and Johnson: Membership on an entity's Board of Directors or advisory committees. Forsberg: Karyopharm: Research Funding; University of Colorado: Ended employment in the past 24 months; Colorado Blood Cancer Institute: Current Employment; Sanofi: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Johnson and Johnson, BMS: Membership on an entity's Board of Directors or advisory committees. Mikkilineni: BiolineRx: Consultancy, Other: advisory board at ASH December 2023; Legend Biotech: Consultancy, Other: advisory board at ASH December 2023. Kaur: Pfizer: Consultancy, Honoraria; Arcellx: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Kedrion: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Kite, a Gilead Company: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Cellectar Biosciences: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Research Funding. Rossi: Adaptive, BMS, Janssen, Karyopharm, JNJ, and Sanofi: Consultancy. Lin: Autolus: Consultancy; Rigel: Consultancy; ADC Therapeutics: Consultancy. Blue: Pfizer Pharmaceuticals, Oncopeptides, Takeda, Abbvie, Janssen, and Kite Pharmaceuticals: Consultancy; Sanofi: Speakers Bureau. Raza: Pfizer: Consultancy, Honoraria; Prothena Biosciences: Consultancy; Kite Pharma: Consultancy. Lin: Caribou: Membership on an entity's Board of Directors or advisory committees; NexImmune: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Genentech: Consultancy; Legend: Consultancy; Celgene: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Sanofi: Consultancy; Regeneron: Consultancy; Bristol-Myers Squibb: Consultancy, Research Funding. McGuirk: Envision: Consultancy; Novartis: Consultancy; Caribou bio: Consultancy; NEKTAR therapeutics: Consultancy; Kite: Consultancy; Autolus: Consultancy; Legend biotech: Consultancy; Sana technologies: Consultancy; Allo Vir: Consultancy; BMS: Consultancy; CRISPR therapeutics: Consultancy. Atrash: Karyopharm: Research Funding; Janssen: Honoraria; Amgen: Research Funding; GSK: Research Funding. Sborov: University of Utah, Huntsman Cancer Institute: Current Employment; Abbvie: Consultancy; Binaytara Foundation: Honoraria; GlaxoSmithKline: Consultancy; Bristol Myers Squibb: Consultancy; Legend Biotech: Consultancy; Parexel, Keosys: Other: IRC; Janssen: Consultancy; Arcellx: Consultancy; AstraZeneca: Consultancy; Bioline: Consultancy; Genentech, Inc.: Consultancy; Pfizer: Consultancy, Research Funding; Society of Utah Medical Oncology: Membership on an entity's Board of Directors or advisory committees; Sanofi: Consultancy. Voorhees: Regeneron: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Research Funding; AstraZeneca: Consultancy; Lava Therapeutics: Consultancy; GSK: Consultancy, Research Funding; Karyopharm: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Anwer: BMS: Consultancy. Patel: Takeda: Consultancy; Johnson & Johnson (Janssen): Consultancy; Pfizer: Consultancy; Abbvie: Consultancy; Genentech: Consultancy; BMS: Consultancy, Other: chair of scientific advisory board ; AstraZeneca: Consultancy; Kite, A Gilead company: Consultancy, Other: scientific advisory board; Merck: Consultancy; Oricel: Consultancy, Other: Chair of scientific board; Poseida: Consultancy; Sanofi: Consultancy; Caribou Sciences: Consultancy. Sidana: Sanofi: Consultancy; BiolineRx: Consultancy; BMS: Consultancy, Research Funding; Legend: Consultancy; Regeneron: Consultancy; Janssen: Consultancy, Research Funding; Novartis: Research Funding; Takeda: Consultancy; Kite, A Gilead company: Consultancy; Abbvie: Consultancy; Oncopeptides: Consultancy; Pfizer: Consultancy. Anderson: Prothena: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: DSMB; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Beigene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Cellectar Biosciences: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Karyopharm: Membership on an entity's Board of Directors or advisory committees; GSK: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Consultancy, Honoraria, Other: Travel Expenses, Research Funding. Richard: Heidelberg Pharma: Research Funding; C4 Therapeutics: Research Funding; Gracell Therapeutics: Other: Steering Committee, Research Funding; Genentech: Membership on an entity's Board of Directors or advisory committees; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Steering Committee, Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Garfall: Tmunity Therapeutics: Research Funding; Novartis: Research Funding; GSK: Consultancy; Amgen: Consultancy; Janssen: Consultancy, Research Funding; Crispr: Research Funding. Lee: Abbvie: Consultancy; Janssen: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Regeneron: Consultancy, Research Funding; Amgen: Research Funding; GlaxoSmithKline: Consultancy, Research Funding; Pfizer: Consultancy; Allogene: Consultancy; Bristol Myers Squibb: Consultancy, Research Funding; Sanofi: Consultancy. Khouri: GPCR Therapeutics, Inc.: Honoraria; Legend: Membership on an entity's Board of Directors or advisory committees; Prothena: Honoraria; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Consultant.

*signifies non-member of ASH