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165 A Phase I Study of Lintuzumab Ac225 in Combination with CLAG-M Chemotherapy in Relapsed/Refractory AML

Program: Oral and Poster Abstracts
Type: Oral
Session: 616. Acute Myeloid Leukemia: Novel Therapy, excluding Transplantation: Advances in immunotherapeutics for management of AML
Hematology Disease Topics & Pathways:
AML, Biological, antibodies, Adult, Diseases, Therapies, Study Population, Myeloid Malignancies
Saturday, December 5, 2020: 12:00 PM

Sameem Abedin, MD1, Guru Subramanian Guru Guru Murthy, MBBS2, Mehdi Hamadani, MD3, Laura C. Michaelis, MD4, Lyndsey Runaas, MD5*, Karen-Sue Carlson, MD, PhD6, Alexandra M. Harrington, MD, MT(ASCP)5 and Ehab L. Atallah, MD7

1Division of Hematology/Oncology, Medical College of Wisconsin, Milwaukee, WI
2Division of Hematology/Oncology, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI
3Division of Hematology and Oncology, Medical College of Wisconsin, Milwaukee, WI
4Division of Hematology/Oncology, Department of Medicine, The Medical College of Wisconsin Inc., Milwaukee, WI
5Medical College of Wisconsin, Milwaukee, WI
6Versiti Blood Research Institute, Medical College of Wisconsin, Milwaukee, WI
7Medical College of Wisconsin, Wauwatosa, WI


Lintuzumab Ac225 is a radiolabeled anti-CD33 antibody, composed of an alpha emitting isotope, Ac225, conjugated with the humanized anti-CD33 monoclonal antibody lintuzumab. As monotherapy, lintuzumab Ac225 was studied as upfront therapy for unfit AML, and nearly 70% of pts achieved a CR/CRi at the highest dose level (2uCi/kg) without significant non-hematologic toxicity. Therefore, we hypothesized that lintuzumab Ac225, when added to the salvage chemotherapy regimen CLAG-M (cladribine, cytarabine, G-CSF, and mitoxantrone), would be tolerable and would improve remission rates in the treatment of relapsed/refractory AML (RR-AML). This investigator-initiated phase I study is the first study to combine radioimmunotherapy with salvage chemotherapy in pts with RR-AML.

Patients and Methods:

Medically fit pts with RR-AML, aged 18 years and older were eligible. Eligibility also required that more than 25% of leukemic blasts must have been CD33 positive by flow cytometry. Induction consisted of G-CSF, 300mcg/d, given D1-6, cladribine 5mg/m2, given D2-6, cytarabine 2g/m2, given D2-6, and mitoxantrone 10mg/m2, given D2-4. Lintuzumab Ac225 was administered as a single dose on either day 7, 8, or 9. This trial had three cohorts, administering lintuzumab Ac225 at a dose of 0.25uCi/kg, 0.50uCi/kg, or 0.75uCi/kg. Treatment consisted of one induction cycle, with subsequent therapy up to physician discretion.


Fifteen pts were evaluable, with a median age of 61 yrs (Figure 1). Slightly less than half of the pts had previously received venetoclax/HMA and slightly more than half had previously had allogeneic HCT. Three pts enrolled into cohort 1 (0.25uCi/kg), nine pts enrolled into cohort 2 (0.5uCi/kg), and three pts enrolled into cohort 3 (0.75uCi/kg). Grade 3 or greater AEs irrespective of causality included febrile neutropenia (n=12), infection (n=8), maculopapular rash (n=2), nausea (n=2), and one patient each with QTc prolongation and tumor lysis syndrome.

Of 15 pts, CR/CRi was observed in 10 (67%) pts. Excluding pts receiving >3 prior lines of therapy, 10/12 (83%) achieved CR/CRi. In cohort 1, 1 patient (33%) achieved remission (1 CR). In cohort 2, 6 pts (67%) achieved remission (3 CR, 2 CRp, 1 CRi). In cohort 3, 3 pts (100%) achieved remission (1 CR, 2 CRp). 7 pts of the 10 with CR/CRi (70%) achieved MRD negativity by flow (Table 2). Two of the 3 patients in cohort 3 were MRD- after therapy and the third had a small number of AML cells detected (0.2%). All pts who were independent for platelet transfusions pre-treatment recovered platelets. Overall, median time to ANC recovery ≥500 was 33 days, and median time to platelet recovery ≥50k was 35 days. 6 pts proceeded to allogeneic HCT after therapy.


We conclude that lintuzumab Ac225 in combination with CLAG-M chemotherapy has a clinically acceptable safety profile. Dose escalation yielded highly encouraging efficacy results for RR-AML. With acceptable safety at 0.75uCi/kg, we have amended this protocol to study a 4th dose level at 1.0uCi/kg. Overall, this regimen represents a safe and potentially effective therapy for medically fit RR-AML pts, particularly as a bridge to allogeneic HCT.

Disclosures: Abedin: Helsinn Healthcare: Honoraria; Agios: Honoraria; Jazz Pharmaceuticals: Honoraria; Pfizer: Research Funding; Helsinn Healthcare: Research Funding; Actinium Pharmaceuticals: Research Funding. Hamadani: Janssen R&D; Incyte Corporation; ADC Therapeutics; Celgene Corporation; Pharmacyclics, Omeros, AbGenomics, Verastem, TeneoBio: Consultancy; ADC Therapeutics: Membership on an entity's Board of Directors or advisory committees; Takeda Pharmaceutical Company; Spectrum Pharmaceuticals; Astellas Pharma: Research Funding; Sanofi Genzyme, AstraZeneca: Speakers Bureau. Michaelis: Jazz Pharmaceuticals: Research Funding. Atallah: Abbvie: Consultancy; Genentech: Consultancy; Jazz: Consultancy; Pfizer: Consultancy; Takeda: Consultancy, Research Funding; Novartis Pharmaceutical Corporation: Consultancy.

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