-Author name in bold denotes the presenting author
-Asterisk * with author name denotes a Non-ASH member
Clinically Relevant Abstract denotes an abstract that is clinically relevant.

PhD Trainee denotes that this is a recommended PHD Trainee Session.

Ticketed Session denotes that this is a ticketed session.

545 Teclistamab in Relapsed Refractory Multiple Myeloma: Multi-Institutional Real-World Study

Program: Oral and Poster Abstracts
Type: Oral
Session: 905. Outcomes Research – Lymphoid Malignancies: Outcomes Research in Myeloma: What's New?
Hematology Disease Topics & Pathways:
Research, Biological therapies, Bispecific Antibody Therapy, health outcomes research, Clinical Research, Therapies, real-world evidence, therapy sequence, Adverse Events
Sunday, December 10, 2023: 1:00 PM

Meera Mohan, MD1, Nishi Shah, MBBS, MPH2, Danny Luan, MD, MPH3, Jorge Monge4*, Mark Forsberg, MD5*, Vineel Bhatlapenumarthi, MD6*, Metodi Balev, MD7*, Anannya Patwari, MD8*, Heloise Cheruvalath, BS9*, Divaya Bhutani, MD10, Sharmilan Thanendrarajan, MD11*, Binod Dhakal, MD12*, Maurizio Zangari, MD11, Samer Al Hadidi, MD, MSc11, Dennis L Cooper, MD13*, Suzanne Lentzsch, MD, PhD14*, Frits van Rhee, MD, PhD11, Anita D'Souza, MD, MS15, Aniko Szabo, PhD16*, Carolina Schinke, MD17 and Rajshekhar Chakraborty18*

1BMT and Cellular Therapy Program, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI
2Oncology, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, NY
3Newyork-Presbyterian Hospital/Weill Cornell Medical College, New York, NY
4Weill Cornell Medicine, New York
5Department of Oncology, Montefiore Medical Center and Albert Einstein College of Medicine, Bronx, NY
6Department of Hematology-Oncology, Medical College of Wisconsin, Milwaukee, WI
7Columbia University Irving Medical Center, New York
8Medical College of Wisconsin, Milwaukee
9Medical College of Wisconsin Medical School, Milwaukee
10Columbia University, College of Physicians and Surgeons, New York, NY
11Myeloma Center, Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, Little Rock, AR
12Medical College of Wisconsin, Wauwatosa, WI
13Montefiore Medical Center, New York
14Columbia University Irving Medical Center, New York Presbyterian, New York, NY
15The Medical College of Wisconsin Inc, Milwaukee, WI
16Medical College of Wisconsin, Milwaukee, WI
17Myeloma Institute, Little Rock, AR
18Columbia University Irving Medical Center, New York, NY

Introduction: Teclistamab is the first BCMA-targeting bispecific antibody (bsAb) that has received FDA approval in RRMM based on the MajesTEC-1 study, which showed a single-agent ORR of 63%. In this report, we present the safety and efficacy of teclistamab since its approval in a real-world multi-institutional cohort.

Methods: All consecutive patients with RRMM treated with at least one dose of standard-of-care teclistamab at 5 academic centers in the US were included in this study. Data including patient demographics, disease, and treatment characteristics at the most recent assessment before starting treatment were retrospectively collected.

Results: A total of 89 patients were treated across 5 academic institutions. The median age was 68 years (range: 37-89), with 48% (n=43) females. Among the patients, 30% (n=27) were Black, 2.2% (n=2) Asian and 12% (n=11) were other minorities. High-risk cytogenetic profile was observed in 65% (n=49/75) of the patients. About 48% (n=39) of the patients exhibited EMD on PET-CT. Four patients had CNS involvement, 1 had pPCL, and 3 had concomitant AL amyloidosis. Furthermore, 98% (n=87) of the patients had triple-class refractory MM, while 85% (n=76) had penta-refractory MM. The median prior lines of therapy were 6 ( range: 3-13) and 80% (n=71) of patients received a prior ASCT. About 37% (n=33) had received prior BCMA-directed therapy, which included BCMA CAR-T in 17, BCMA BsAb in 5, and Belantamab mafadotin in 11 patients .Table 1 compares this patient cohort with the MajesTEC-1 study population. Grade 1/2 CRS was observed in 48% (n=43) of patients, while 3% (n=3) experienced grade 4 CRS. Grade 1/2 ICANS was noted in 7% (n=6) of patients, grade 3/4 in 4.4% (n=4), and grade 5 in 1 patient. Steroids were utilized in 22% (n=16) of patients, while tocilizumab was administered in 44% (n=32) of patients. Notably, step-up dosing of teclistamab was administered entirely in the outpatient setting in 9% (n=8) of patients. For the remaining, inpatient step-up dosing was administered, and the median hospitalization duration was 10 days. At a median follow-up of 1.35 months (range: 0.16-4.38), the ORR among the evaluable patients was 55%, with rates of ≥ VGPR and PR at 37% (n=28) and 18% (n=13), respectively. The 3-month PFS rate was 54% (95% CI: 43%, 69%), while the 3-month OS rate was 80% (95% CI: 71%, 90%). Multivariate analysis did not reveal any significant associations between disease response and the following factors: number of prior lines of therapy (HR 1.03, 95% CI 0.76-1.42), baseline lymphocyte counts (HR 0.98, 95% CI 0.47-2.02), high-risk cytogenetics (HR 0.38, 95% CI 0.09-1.39) and the presence of extramedullary disease (HR 0.56, 95% CI 0.15-1.93). There was a trend towards worse ORR in patients with prior exposure to BCMA targeting agents, albeit not quite significant (HR 0.28, 95% CI 0.07-1.04, p=0.065). There were 61 infectious events with 50%, 45% and 5% of these being viral, bacterial, and fungal infections, respectively. The most common sources of infections were upper respiratory tract infections/pneumonias (33%), blood borne infections including bacteremia and viremia (27%) and urinary tract infections (11%). The cumulative incidence of any infection at 3 months was 55% and grade 3/4 infections were seen in 55% (n= 54) of cases. There was one grade 5 infection noted in this study due to COVID 19 pneumonia. Primary IVIG and PJP prophylaxis were used in 40% (n=34) and 51% (n=43) of patients, respectively and the use of such was associated with a significant reduction of infectious events (26/51 [51%] of any infectious event for no IVIG use vs 13/34 [38%] for IVIG use, p= 0.015). The results will be updated with longer follow-up at the meeting.

Conclusion : In this large real-world, multi-institutional study including a diverse cohort of heavily pretreated patients with triple-class and penta-refractory MM, including approximately 40% with prior BCMA exposure, teclistamab demonstrated a respectable ORR of 55% with ≥ VGPR in 37% of cases. The incidence of Grade 3 or higher infections at 3 months remained high at 56%, however the use of prophylactic measures, including primary IVIG prophylaxis was associated with a significant reduction of all infections and should be strongly considered in patients receiving teclistamab.

Disclosures: Mohan: MJH life sciences: Honoraria; Institutional KL2 Award: Other: Research Grant; Sanofi S.A: Consultancy, Research Funding; Takeda Pharmaceutical Company: Research Funding; Ionis Pharmaceuticals: Research Funding; Bristol-Myers Squibb Company: Research Funding; Celgene Corporation: Research Funding; Novartis: Research Funding; Amgen Inc: Research Funding; Blood Cancer Today: Honoraria; MashupMD: Honoraria; GlaxoSmithKline plc: Research Funding; Bristol myers squibb/Celgene: Consultancy; Pfizer: Consultancy. Bhutani: Sanofi: Consultancy, Research Funding. Lentzsch: Janssen: Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy; Clinical Care Options: Honoraria; Celgene: Research Funding; Oncopeptide: Membership on an entity's Board of Directors or advisory committees; Sanofi: Research Funding; Regeneron: Honoraria; Takeda: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Adaptive: Consultancy, Membership on an entity's Board of Directors or advisory committees; Caelum Biosciences: Membership on an entity's Board of Directors or advisory committees, Patents & Royalties; BMS: Membership on an entity's Board of Directors or advisory committees; Alexion: Consultancy, Membership on an entity's Board of Directors or advisory committees. van Rhee: GlaxoSmithKline: Consultancy; Janssen Pharmaceuticals: Research Funding; Bristol Myers Squibb: Research Funding; EUSA Bio: Consultancy; Adicet Bio: Consultancy. D'Souza: Janssen, Prothena: Consultancy; Imbrium, Pfizer, Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Abbvie, Sanofi, Takeda, TeneoBio, Caelum, Prothena: Research Funding. Schinke: Janssen: Consultancy, Honoraria; Pfizer: Honoraria; Arcellx: Consultancy. Chakraborty: Sanofi: Consultancy, Honoraria; Adaptive Biotech: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Genentech: Research Funding; AbbVie: Research Funding.

*signifies non-member of ASH