Session: 907. Outcomes Research: Plasma Cell Disorders: Poster II
Hematology Disease Topics & Pathways:
Research, Clinical Research, Plasma Cell Disorders, Supportive Care, Diseases, Real-world evidence, Treatment Considerations, Lymphoid Malignancies
Methods: We conducted a two-part study within the US MM Immunotherapy Consortium. Firstly, we analyzed data from commercial idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel) recipients (leukapheresis cutoff December 31, 2023) to identify the prevalence of CRS, ICANS, or death between Weeks 5-8 (D+29 to D+56) following CAR-T (Day 0). Patients with index hospital stays lasting over 4 weeks and patients with <8 weeks of post-CAR-T follow-up were excluded. Secondly, we surveyed Consortium members about the prevalence of impaired driving risk (defined as “anything that could impair a patient’s ability to drive safely, e.g. seizures, altered mental status, blindness, etc.”) and used 1-5 Likert scales to gauge the perceived importance of driving restrictions (assuming no FDA guidance existed) during Weeks 0-4 vs 5-8. This anonymous IRB-exempted survey was distributed via email to 63 CAR-T-prescribing physicians within the Consortium.
Results: Of 553 analyzed patients, 41% (n=224) had received cilta-cel and 59% (n=329) ide-cel. The median age was 64 (IQR 58-70), 42% (n=231) were female, 78% White (n=434), 13% (n=72) Black, and 9% (n=51) Hispanic. ECOG PS at infusion was ≥2 in 11% (n=63) of patients, and 5% (n=28) had had previous CNS co-morbidities such as prior strokes. One patient (0.2%) developed Grade 2 CRS during Weeks 5-8 (onset D+47, resolution one day later); no patients had de novo ICANS after D+28. There were 16 cases of non-ICANS neurotoxicity (including 2 cases of Parkinsonism) diagnosed a median of 24 days after CAR-T (range: 17-147 days), of which 3 cases (all non-Parkinsonian) were first diagnosed during Weeks 5-8. There were 10 deaths (2%) during Weeks 5-8, one due to infection and the remainder from progressive MM.
The survey was completed by 45 oncologists (71% response rate), 41 of whom had managed both >5 ide-cel and >5 cilta-cel recipients. Regarding impaired driving during Weeks 0-4, 20% of physicians felt this was never a risk, 36% a risk for 1-2% of patients, 29% a risk for 3-10% of patients, and 16% a risk for >10% of patients. The distribution was significantly different (p < 0.01) for Weeks 5-8: 49% never a risk, 36% a risk for 1-2% of patients, 16% a risk for 3-10% of patients, while no respondents felt this remained a risk for >10% of patients. For Weeks 0-4, 73% agreed that patients should be advised not to drive while 9% disagreed. In contrast, for Weeks 5-8, 14% of physicians agreed with driving restrictions while 78% disagreed (p < 0.01 compared to Weeks 0-4).
Discussion: Our two-part study demonstrates that driving restrictions following Week 4 after CAR-T therapy in MM may not be required. The incidence of de novo CRS or any-type neurotoxicity being diagnosed during Weeks 5-8 was <1%, and – if such toxicities developed – patients and physicians could be expected to set appropriate restrictions at that juncture. While 73% of CAR-T-prescribing oncologists agreed that patients should refrain from driving during Weeks 0-4, 78% disagreed with this recommendation during Weeks 5-8. These findings complement other real-world studies (Wesson, Dima, et al, TCT 2024; Ahmed et al, Blood Advances 2024) reporting the rarity of CRS and ICANS after the first month in both MM and lymphoma. Our study is limited by a lack of patient-reported data, which was done intentionally to avoid asking patients about activities undertaken against medical advice. Nevertheless, we believe that narrowing universal driving restrictions to Weeks 0-4 following CAR-T therapy would constitute an evidence-based modification to the package inserts for ide-cel and cilta-cel.
Disclosures: 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. Khouri: GPCR Therapeutics: Honoraria; Legend Biotech: Honoraria; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy. Janakiram: JANNSEN: Honoraria, Research Funding; BMS: Honoraria, Research Funding; LEGEND: Honoraria, Research Funding; FATE THERAPEUTICS: Research Funding. Cicero: BMS, Novartis: Research Funding. 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. Jain: Bristol Myers Squibb, Incyte, Abbvie, CTI, Kite, Cogent Biosciences, Blueprint Medicine, Telios pharma, Protagonist therapeutics, Galapagos, Tscan therapeutics, Karyopharm, Morphosys: Membership on an entity's Board of Directors or advisory committees; CTI Biopharma, Kartos therapeutics, Incyte, Bristol Myers Squibb: Research Funding. Afrough: Sanofi: Honoraria, Other; Karyopharm Therapeutics: Honoraria, Other; Bristol-Myers Squibb: Honoraria, Other; K36 Therapeutics: Research Funding; Adaptive Biotech: Research Funding; Abbvie: Research Funding. Ferreri: Janssen: Consultancy; Affimed: Current holder of stock options in a privately-held company. Mikkilineni: BiolineRx: Consultancy, Other: advisory board at ASH December 2023; Legend Biotech: Consultancy, Other: advisory board at ASH December 2023. Peres: Karyopharm Therapeutics: Research Funding; Bristol Myers Squibb: Research Funding. Freeman: BMS: Consultancy, Honoraria, Research Funding; Celgene: Consultancy; Sanofi: Consultancy; Abbvie: Consultancy; Seattle Genetics: Consultancy; Janssen: Consultancy, Research Funding; ONK therapeutics: Consultancy; Amgen: Consultancy; Incyte: Consultancy; Roche/Genentech: Research Funding. Midha: Pfizer: Consultancy; Janssen: Consultancy. Beitinjaneh: Lyell: Research Funding; CRISPOR: Research Funding; Atara: Research Funding; Autolus: Consultancy, Research Funding; Kite, a Gilead Company: Honoraria, Research Funding; Tessa: Research Funding. Davis: Janssen Biotech: Speakers Bureau. Wagner: Jazz: Research Funding; Pfizer: Consultancy. Forsberg: Colorado Blood Cancer Institute: Current Employment; Karyopharm: Research Funding; Johnson and Johnson, BMS: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; University of Colorado: Ended employment in the past 24 months. Sborov: Paraxel: Other: Independent review committee; Celgene: Honoraria; Amgen, Celgene, and Janssen, GlaxoSmithKline, Abbvie, Pfizer, Astra Zeneca, Bioline, Sanofi, and Genentech: Consultancy; Pfizer: Research Funding; Janssen, Karyopharm: Membership on an entity's Board of Directors or advisory committees. 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. Reshef: Cabaletta: Research Funding; TScan: Consultancy, Research Funding; Orca Bio: Consultancy; BMS: Research Funding; Takeda: Research Funding; Synthekine: Research Funding; CareDx: Research Funding; Incyte: Consultancy, Research Funding; TCR2: Research Funding; Sana Biotechnology: Consultancy; Quell Biotherapeutics: Consultancy; Autolus: Consultancy; Bayer: Consultancy; Atara Biotherapeutics: Research Funding; Sanofi: Research Funding; Immatics: Research Funding; Abbvie: Research Funding; J&J: Research Funding; Genentech: Research Funding; Precision Biosciences: Research Funding; Gilead Sciences: Consultancy, Research Funding; Allogene: Consultancy. Dhakal: Acrellx: Research Funding; Janssen: Honoraria, Research Funding, Speakers Bureau; Pfizer: Consultancy, Honoraria, Speakers Bureau; Sanofi: Research Funding; Carsgen: Research Funding; Bristol Myers Squibb: Honoraria, Research Funding; Karyopharm: Honoraria, Speakers Bureau; Genentech: Consultancy, Honoraria; C4 therapeutics: Research Funding; Medical College of Wisconsin: Current Employment. Bachanova: Citius: Research Funding; Incyte: Research Funding. McGuirk: NEKTAR therapeutics: Consultancy; Legend biotech: Consultancy; Sana technologies: Consultancy; Autolus: Consultancy; Envision: Consultancy; CRISPR therapeutics: Consultancy; Caribou bio: Consultancy; Novartis: Consultancy; Allo Vir: Consultancy; Kite: Consultancy; BMS: Consultancy. Voorhees: AstraZeneca: Consultancy; Regeneron: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Karyopharm: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Research Funding; BMS: 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; Lava Therapeutics: Consultancy; GSK: Consultancy, Research Funding; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Anderson: Janssen: 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; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Karyopharm: 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; Prothena: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: DSMB; Amgen: Consultancy, Honoraria, 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; Beigene: 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; BMS: Consultancy, Honoraria, Other: Travel Expenses, Research Funding. Lin: Sanofi: Consultancy; Regeneron: Consultancy; Caribou: Membership on an entity's Board of Directors or advisory committees; Legend: Consultancy; NexImmune: Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Research Funding; Pfizer: Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Genentech: Consultancy. Martin: Janssen: Research Funding; Poseida: Research Funding; GSK, Pfizer, Roche: Honoraria; BMS: Research Funding; Sanofi: Research Funding. Sidana: Abbvie: Consultancy; BMS: Consultancy, Research Funding; BiolineRx: Consultancy; Janssen: Consultancy, Research Funding; Regeneron: Consultancy; Pfizer: Consultancy; Sanofi: Consultancy; Takeda: Consultancy; Legend: Consultancy; Novartis: Research Funding; Kite, A Gilead company: Consultancy; Oncopeptides: Consultancy. Patel: Johnson & Johnson (Janssen): Consultancy; AstraZeneca: Consultancy; Sanofi: Consultancy; Pfizer: Consultancy; Takeda: Consultancy; BMS: Consultancy, Other: chair of scientific advisory board ; Merck: Consultancy; Kite, A Gilead company: Consultancy, Other: scientific advisory board; Genentech: Consultancy; Poseida: Consultancy; Abbvie: Consultancy; Caribou Sciences: Consultancy; Oricel: Consultancy, Other: Chair of scientific board. Hansen: Pfizer: Consultancy; Janssen: Consultancy; Karyopharm: Consultancy, Research Funding; BMS: Consultancy, Research Funding. Cowan: HopeAI: Consultancy, Current holder of stock options in a privately-held company; Harpoon: Research Funding; Caelum: Research Funding; Sanofi: Consultancy, Research Funding; Regeneron: Research Funding; IgM biosciences: Research Funding; Nektar: Research Funding; Juno/Celgene: Research Funding; BMS: Consultancy, Research Funding; Adaptive Biotechnologies: Consultancy, Research Funding; Abbvie: Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Sebia: Consultancy. Kaur: Kite, a Gilead Company: Consultancy, Membership on an entity's Board of Directors or advisory committees; 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; 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; AbbVie: Research Funding; 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.
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