-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.

2811 Updated Results of the Combination of Mini-Hyper-CVD with Inotuzumab Ozogamicin and Blinatumomab in Patients with Relapsed/Refractory B-Cell ALL

Program: Oral and Poster Abstracts
Session: 613. Acute Lymphoblastic Leukemias: Therapies Excluding Allogeneic Transplantation: Poster II
Hematology Disease Topics & Pathways:
ALL, Lymphoid Leukemias, Research, Clinical trials, Clinical Research, Diseases, Lymphoid Malignancies
Sunday, December 8, 2024, 6:00 PM-8:00 PM

Diane Habib, MD1*, Hagop M. Kantarjian, MD2, Fadi G. Haddad, MD3, Nicholas J. Short, MD3, Nitin Jain, MD3, Jayastu Senapati, MD, DM, MBBS3, Kelly S. Chien, MD4, Guillermo Garcia-Manero, MD3, Zena Komrokji5*, Tapan M. Kadia, MD3, Naval Daver, MD6, Courtney D. DiNardo, MD, MSc7, Koji Sasaki, MD3, Rebecca Garris3*, Farhad Ravandi, MBBS8 and Elias Jabbour, MD9

1HCA Houston Healthcare Kingwood, Spring, TX
2The University of Texas MD Anderson Cancer Center, Houston, TX
3Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX
4Department of Leukemia, MD Anderson, Houston, TX
5Department of Malignant Hematology, Moffitt Cancer Center, Tampa, FL
6MD Anderson Cancer Center, Houston, TX
7Department of Leukemia, UT MD Anderson Cancer Center, Houston, TX
8Department of Leukemia, University of Texas- MD Anderson Cancer Center, Houston, TX
9Department of Leukemia, University of Texas M.D. Anderson Cancer Ctr., Houston, TX

Background: The sequential combination of mini-Hyper-CVD (mini-HCVD) with inotuzumab ozogamicin (INO) and blinatumomab (Blina) improved the outcome of patients (pts) with relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL) with a tolerable safety profile. Here, we report updated results from a phase II trial including the “dose-dense” (D-D) administration of INO and Blina in combination with chemotherapy with longer follow-up.

Methods: Pts ≥18 years with R/R B-ALL were eligible for this phase II trial. All pts received mini-HCVD (cyclophosphamide and dexamethasone at 50% dose reduction, no anthracycline, methotrexate at 75% dose reduction, cytarabine at 0.5 g/m2 x4 doses) and INO. In Cohort 1, pts were treated with mini-HCVD for 8 cycles and INO at 1.3-1.8 mg/m2 on Day (D)3 of Cycle 1, and 0.8-1.3 mg/m2 during Cycles 2-4. Maintenance consisted of POMP for 36 months (mo). Following a protocol amendment starting pt #68 (Cohort 2), INO was given at a fractionated dose of 0.6 mg/m2 on D2 and 0.3 mg/m2 on D8 of Cycle 1, then 0.3 mg/m2 on D1 and D8 in Cycles 2-4 for a cumulative dose of 2.7mg/m2; Blina consolidation was added for 4 cycles. Maintenance was 18 mo of POMP alternating with Blina every 3 mo. Starting pt #111, Blina was introduced earlier in a D-D fashion (D-D cohort). In addition to mini-HCVD and INO, pts received Blina from D4 to D21 of each 28-day cycle for up to 6 cycles. CD20+ pts received rituximab on D2 and D8 of the first 4 cycles. All pts received Ursodiol for the prevention of hepatic sinusoidal obstruction syndrome (SOS).

Results: From February 2013 to February 2024, 133 pts were treated with a median age of 37 years (range,17-87); 66 (50%) were males. 67 pts were treated in Cohort 1, 44 in Cohort 2, and 22 in the D-D cohort. 41 pts (31%) had high-risk cytogenetics. CRLF2 rearrangement was found in 16/87 pts (18%) and TP53 mutation in 24/79 pts (30%). 25 pts (19%) had prior ASCT. 98 pts (74%) were treated in Salvage (S)1, 19 pts (14%) in S2, and 16 pts (12%) in S3+.

Among 132 evaluable pts, the overall response rate (ORR) was 86% (CR, 65%). The ORR was 76% in Cohort 1 (CR, 60%), 93% in Cohort 2 (CR, 66%), and 100% in the D-D cohort (CR, 81%). 7 pts (5%) died within 4 weeks of therapy, all in Cohort 1. The rate of measurable residual disease (MRD) negativity by flow cytometry was 53% after Cycle 1 and 85% overall. These rates were 51% and 82% in Cohort 1, 46% and 85% in Cohort 2, and 74% and 95% in the D-D cohort, respectively. In the D-D cohort, 16 of 17 pts (94%) who had NGS MRD testing achieved negative MRD status. Fifty-seven pts (43%) underwent ASCT and 12 pts (9%) received CAR T-cell therapy.

After a median follow-up of 40 mo (range, 3-136) for the entire cohort, the 3-year OS rate was 45% and the relapse-free survival rate was 44%. Pts treated in S1 had better OS compared to pts treated in S2+ (3-year OS, 54% vs 20%; P=0.0001). In a 4-month landmark analysis, the 3- year OS was 60% in patients who underwent transplant and 56% in those who did not (P=0.61).

Outcomes appear superior with the D-D regimen. The 1-year OS rate was 51% in Cohort 1, 66% in Cohort 2, and 90% in the D-D cohort (P=0.006). Among patients in S1, these rates were 63%, 66%, and 94%, respectively (P=0.08). SOS was observed in 10 pts: 9 (13%) with the initial trial design and 1 (2%) after the first amendment with fractionated INO dosing (P=0.02).

Conclusion: The combination of mini-HCVD, INO and Blina is safe and effective in R/R B-ALL. Introducing Blina and fractionating INO seem to improve the safety and efficacy of this combination. Using a D-D approach resulted in high rates of deep and early MRD responses and promising survival outcomes, which may be better than the sequential use of these agents.

Disclosures: Kantarjian: AbbVie, Amgen, Ascentage, Ipsen Biopharmaceuticals, KAHR Medical, Novartis, Pfizer, Shenzhen Target Rx, Stemline,Takeda: Consultancy, Honoraria. Short: Novartis: Honoraria; BeiGene: Honoraria; Autolus: Honoraria; Sanofi: Honoraria; Adaptive Biotechnologies: Honoraria; Takeda Oncology: Honoraria, Research Funding; Xencor: Research Funding; Astellas Pharma, Inc.: Honoraria, Research Funding; Amgen: Honoraria; Stemline Therapeutics: Research Funding; NextCure: Research Funding; Pfizer Inc.: Honoraria; GSK: Consultancy, Research Funding. Jain: Servier: Research Funding; BeiGene: Consultancy, Honoraria, Other: Travel Support; CareDx: Consultancy, Honoraria, Other: Travel Support; MEI Pharma: Consultancy, Honoraria, Other: Travel Support; Medisix: Research Funding; Janssen: Consultancy, Honoraria, Other: Travel Support; Ipsen: Consultancy, Honoraria, Other: Travel Support; Precision Biosciences: Consultancy, Honoraria, Other: Travel Support, Research Funding; Aprea Therapeutics: Research Funding; Kite, a Gilead Company: Consultancy, Honoraria, Other: Travel Support, Research Funding; NovalGen: Research Funding; Pharmacyclics: Consultancy, Honoraria, Other: Travel Support, Research Funding; Genentech: Consultancy, Honoraria, Other: Travel Support, Research Funding; Bristol Myers Squibb: Consultancy, Honoraria, Other: Travel Support, Research Funding; ADC Therapeutics: Research Funding; Fate Therapeutics: Research Funding; TransThera Sciences: Research Funding; Pfizer: Research Funding; Cellectis: Consultancy, Honoraria, Other: Travel Support, Research Funding; TG Therapeutics: Consultancy, Honoraria, Other: Travel Support; Dialectic Therapeutics: Research Funding; Incyte: Research Funding; Loxo Oncology: Research Funding; MingSight: Honoraria, Research Funding; Newave: Research Funding; Takeda: Research Funding; AstraZeneca: Consultancy, Honoraria, Other: Travel Support, Research Funding; Adaptive Biotechnologies: Consultancy, Honoraria, Other: Travel Support, Research Funding; AbbVie: Consultancy, Honoraria, Other: Travel Support, Research Funding. Chien: AbbVie: Consultancy; Rigel Pharmaceuticals: Consultancy. Garcia-Manero: AbbVie: Research Funding; Aprea: Research Funding; Helsinn: Other: Personal fees; Forty Seven: Research Funding; Astex: Research Funding; Helsinn: Research Funding; Astex: Other: Personal fees; Janssen: Research Funding; Genentech: Research Funding; Onconova: Research Funding; H3 Biomedicine: Research Funding; Merck: Research Funding; Novartis: Research Funding; Bristol Myers Squibb: Other: Personal fees, Research Funding; Curis: Research Funding; Genentech: Other: Personal fees; Amphivena: Research Funding. Kadia: Rigel: Honoraria; BMS: Consultancy, Research Funding; Pfizer: Research Funding; Amgen: Research Funding; DrenBio: Consultancy, Research Funding; JAZZ: Research Funding; Servier: Consultancy; Abbvie: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; Incyte: Research Funding; ASTEX: Research Funding; AstraZeneca: Research Funding; Cellenkos: Research Funding; Novartis: Honoraria; Ascentage: Research Funding; Regeneron: Research Funding; Sellas: Consultancy, Research Funding. Daver: KITE: Research Funding; Novartis: Consultancy; Celgene: Consultancy; Menarini Group: Consultancy; Trovagene: Research Funding; Astellas: Consultancy, Research Funding; Jazz: Consultancy; Trillium: Consultancy, Research Funding; Syndax: Consultancy; Agios: Consultancy; FATE Therapeutics: Other: Consulting Fees, Research Funding; Glycomimetics: Research Funding; Arog: Consultancy; Hanmi: Research Funding; Genentech: Consultancy, Research Funding; Shattuck Labs: Consultancy; Novimmune: Research Funding; Gilead: Consultancy, Research Funding; Servier: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Bristol Myers Squibb: Consultancy, Research Funding; Daiichi-Sankyo: Consultancy, Research Funding. DiNardo: Genetech: Honoraria; Astex: Research Funding; Foghorn: Research Funding; Astellas: Consultancy, Honoraria; Rigel: Research Funding; Gilead: Consultancy; Loxo: Research Funding; ImmuneOnc: Research Funding; Jazz: Consultancy, Honoraria; Schrodinger: Consultancy, Honoraria; Servier: Consultancy, Honoraria, Other: meetingsupport, Research Funding; Riegel: Honoraria; Immunogen: Honoraria; AstraZeneca: Honoraria; GenMab: Consultancy, Honoraria, Other: data safety board; GSK: Consultancy, Honoraria; BMS: Consultancy, Honoraria, Research Funding; Amgen: Consultancy; Notable Labs: Honoraria; Cleave: Research Funding; Abbvie: Consultancy, Honoraria, Research Funding; Stemline: Consultancy. Sasaki: Daiichi-Sankyo: Consultancy; Chugai: Other: Lecture fees; Enliven: Research Funding; Otsuka: Other: Lecture fees; Pfizer: Consultancy; Novartis: Consultancy, Research Funding. Ravandi: BMS: Consultancy, Honoraria; Syros: Consultancy, Honoraria, Research Funding; Amgen: Research Funding; Xencor: Research Funding; Prelude: Consultancy, Honoraria, Research Funding; Astellas: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Astyex/Taiho: Research Funding; Syndax: Honoraria. Jabbour: AbbVie, Adaptive Biotechnologies, Amgen, Ascentage Pharma Group, Pfizer, Takeda: Research Funding; AbbVie, Adaptive Biotechnologies, Amgen, Astellas Pharma, BMS, Genentech, Incyte, Pfizer, Takeda: Consultancy.

*signifies non-member of ASH