Patient Expectations and Perceptions of Treatment in CARTITUDE-1: Phase 1b/2 Study of Ciltacabtagene Autoleucel in Relapsed/Refractory Multiple Myeloma
Authors: Cohen Adam D. , Hari Parameswaran , Htut Myo , Berdeja Jesus G. , Madduri Deepu , Usmani Saad Z. , Allred Alicia J. , Olyslager Yunsi , Banerjee Arnob , Goldberg Jenna D. , Schecter Jordan M. , Jackson Carolyn C. , Gries Katharine S. , Fastenau John , Deraedt William , Carrasco Marlene J. , Akram Muhammad , Hossain Farah , Crawford Sigrid , Morrison Ross , Doward Lynda , Jakubowiak Andrzej , Jagannath Sundar 
Published: November 2020

Background: Patients (pts) with multiple myeloma (MM) experience health-related quality of life (HRQoL) decrement due to symptoms such as fatigue, pain, and insomnia. Pt perspectives of their disease and treatment expectations can help inform clinical decision-making. The phase 1b/2 CARTITUDE-1 study (NCT03548207) is evaluating the efficacy and safety of ciltacabtagene autoleucel (cilta-cel; JNJ-68284528; LCAR-B38M CAR-T cells), a chimeric antigen receptor T (CAR-T) cell therapy with 2 B-cell maturation antigen-targeting single-domain antibodies, in pts with relapsed/refractory (R/R) MM. An exploratory objective is to describe pretreatment goals and expectations and post-treatment experience of cilta-cel using qualitative interviews.
Methods: Pts (aged ≥18 years) with an MM diagnosis per International Myeloma Working Group criteria who had received ≥3 prior regimens or were double-refractory to a proteasome inhibitor and immunomodulatory drug, and who had received an anti-CD38 antibody were included. On Day 1, cilta-cel (target dose 0.75×106 [range 0.5-1.0×106] CAR+ viable T cells/kg) was given as a single infusion 5-7 days after start of lymphodepletion (cyclophosphamide 300 mg/m2 + fludarabine 30 mg/m2 daily for 3 days). In the phase 2 portion, pts had the option to participate in structured qualitative interviews conducted pretreatment, at Day 100 ± 30 (end of cilta-cel post-infusion period), and Day 184 ± 30 (during post-treatment phase). Pretreatmentinterviews: pts were asked open-ended questions about their experience living with MM and expectations of cilta-cel. Day 100and184interviews: pts were asked about changes to their MM symptoms and daily life impacts, experiences with cilta-cel, and if pretreatment expectations were met. Content analysis of qualitative data was performed by extracting themes from the transcripts based on a coding dictionary.
Results: Of 68 pts in the phase 2 portion, 36 (55.6% male; median age: 62.5 years [range: 46-77]) completed ≥1 interview (pretreatment: n=27; Day 100: n=23; Day 184: n=24); 24 pts completed &gt;1 interview and 14 completed all 3 interviews. The most common symptoms reported at the pretreatment interview, pain (85.2% of pts) and fatigue (74.1% of pts), were also frequently considered to have the greatest impact on pts' lives (29.6% and 25.9%, respectively) and identified as symptoms that pts would most like to see improved (25.9% and 33.3%, respectively). After cilta-cel therapy, at Day 100 and 184 interviews, respectively, the proportions of pts who reported pain (21.7% and 29.2%) and fatigue (34.8% and 20.8%) decreased. At the pretreatment interview, pts most frequently reported that MM impacted relationships (92.6%), psychological and emotional functioning (88.9%), and activities of daily living (66.7%). In longitudinal analyses of pts who completed &gt;1 interview, most pts reported either improvement or no change in these impacts at Day 100 and 184 interviews, respectively, (relationships [50.0% and 58.3%], psychological and emotional functioning [77.3% and 83.3%], and activities of daily living [59.1% and 62.5%]), suggesting a diminished impact of MM on HRQoL following cilta-cel treatment.
The most common expectations of cilta-cel reported by pts at the pretreatment interview were remission (40.7%), extended life expectancy (14.8%), less treatment (11.1%), and cure (11.1%). The most frequently reported treatment hopes were remission (40.7%), return to perceived normalcy (25.9%), cure (25.9%), and extended life expectancy (22.2%). Key areas in which pts would consider changes to be meaningful with cilta-cel treatment were improved MM symptoms (70.4%), return to perceived normalcy (40.7%), and the ability to be more physically active (33.3%). At Day 100 and 184 interviews, respectively, 78.3% and 91.7% of pts reported that their expectations of cilta-cel were met or exceeded (Figure A). Furthermore, most pts at the Day 100 and 184 interviews (52.2% and 70.8%, respectively) perceived their experience with cilta-cel as exclusively better than their previous treatment experiences (Figure B).
Conclusions: Pts treated with cilta-cel experienced reductions in both symptoms associated with R/R MM and impact of MM on HRQoL. Pretreatment expectations of cilta-cel were met or exceeded, and most pts reported their experience was better than with prior MM treatments.

Disclosures
Cohen: Novartis: Other: Patents/Intellectual property licensed, Research Funding; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees; Takeda,: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline: Membership on an entity's Board of Directors or advisory committees; Kite Pharma: Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Genentech/Roche: Membership on an entity's Board of Directors or advisory committees. Hari:GSK: Consultancy; Amgen: Consultancy; Incyte Corporation: Consultancy; Janssen: Consultancy; BMS: Consultancy; Takeda: Consultancy. Htut:City of Hope Medical Center: Current Employment. Berdeja:CURIS: Research Funding; Constellation: Research Funding; Janssen: Consultancy, Research Funding; Vivolux: Research Funding; Abbvie: Research Funding; Amgen: Consultancy, Research Funding; Poseida: Research Funding; Kesios: Research Funding; EMD Sorono: Research Funding; Glenmark: Research Funding; Novartis: Research Funding; Legend: Consultancy; Kite Pharma: Consultancy; Acetylon: Research Funding; Prothena: Consultancy; Celgene: Consultancy, Research Funding; Genentech, Inc.: Research Funding; Teva: Research Funding; Servier: Consultancy; Takeda: Consultancy, Research Funding; Cellularity: Research Funding; Lilly: Research Funding; Bluebird: Research Funding; CRISPR Therapeutics: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Bioclinica: Consultancy; Karyopharm: Consultancy. Madduri:Janssen: Consultancy, Honoraria; GSK: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Speaking Engagement, Speakers Bureau; Legend: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Speaking Engagement, Speakers Bureau; Takeda: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Foundation Medicine: Consultancy, Honoraria; Kinevant: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Speaking Engagement, Speakers Bureau; AbbVie: Consultancy, Honoraria. Usmani:Celgene: Other; Amgen: Consultancy, Honoraria, Other: Speaking Fees, Research Funding; BMS, Celgene: Consultancy, Honoraria, Other: Speaking Fees, Research Funding; Abbvie: Consultancy; Sanofi: Consultancy, Honoraria, Research Funding; GSK: Consultancy, Research Funding; Pharmacyclics: Research Funding; Incyte: Research Funding; Janssen: Consultancy, Honoraria, Other: Speaking Fees, Research Funding; Merck: Consultancy, Research Funding; SkylineDX: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; Takeda: Consultancy, Honoraria, Other: Speaking Fees, Research Funding; Array Biopharma: Research Funding. Allred:Janssen: Current Employment. Olyslager:Janssen: Current Employment. Banerjee:Janssen: Current Employment. Goldberg:Johnson & Johnson: Current Employment, Current equity holder in publicly-traded company. Schecter:Janssen: Current Employment. Jackson:Memorial Sloan Kettering Cancer Center: Consultancy; Janssen: Current Employment. Gries:Janssen: Current Employment, Current equity holder in publicly-traded company. Fastenau:Janssen: Current Employment, Current equity holder in publicly-traded company. Deraedt:Janssen: Current Employment, Current equity holder in publicly-traded company. Carrasco:Legend Biotech USA Inc.: Current Employment. Akram:Legend Biotech USA Inc.: Current Employment. Hossain:Legend Biotech USA Inc.: Current Employment. Crawford:RTI Health Solutions: Current Employment. Morrison:RTI Health Solutions: Current Employment. Doward:RTI Health Solutions: Current Employment. Jakubowiak:AbbVie, Amgen, BMS/Celgene, GSK, Janssen, Karyopharm: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Adaptive, Juno: Consultancy, Honoraria. Jagannath:BMS, Janssen, Karyopharm, Legend Biotech, Sanofi, Takeda: Consultancy.