ASH 2023: High Dose Targeted Radiotherapy via Iomab-B Prior to BMT Produces Durable Complete Remissions

Study Design:

65th ASH Annual Meeting & Exposition

San Diego, CA

Dec 9-12, 2023

PUBLICATION #3529

High-Dose Targeted Radiation with 131I-apamistamab Prior to HCT Demonstrated

a Dose-Response for Durable Complete Remission in Patients with R/R AML

Mark R. Litzow, MD1, George Chen, MD2,3, Boglarka Gyurkocza, MD4, Rajneesh Nath, MD5*, Stuart Seropian, MD6, Hannah Choe, MD7, Camille N. Abboud, MD8, Nebu Koshy, MD9*, Ben K. Tomlinson, MD10, Sunil Abhyankar, MD11, James Foran, MD12, Sameem Abedin, MD13, Zaid Al-Kadhimi, MD14,15*, Partow Kebriaei, MD16, Mitchell Sabloff, MSc, MD, FRCPC17, Johnnie J. Orozco, MD, PhD18, Katarzyna Joanna Jamieson, MD19*, Margarida Magalhaes-Silverman, MD20, Koen Van Besien, MD, PhD21,22, Michael W. Schuster, MD23, Arjun D. Law, MD24*, Sebastian A. Mayer, MD25, Hillard M. Lazarus, MD26, Eugene Leung, MD, FRCPC27*, Ming-Kai Chen, MD, PhD28*, Mona Natwa, MD29*, Jennifer Spross, MA30*, Kate L Li, PhD30*, Norman Nagl, PhD30*, Elaina Haeuber, MS30*, Madhuri Vusirikala, MD30*, Akash Nahar, MD, MPH30*, Brenda M. Sandmaier, MD31, John M. Pagel, MD, PhD32, Sergio A. Giralt, MD33, Avinash Desai, M.D30*, Richard L. Wahl, MD34*, Neeta Pandit-Taskar, MD33*, Patrik Brodin, PhD, DABR30* and Patrick J. Stiff, MD35

1Division of Hematology, Mayo Clinic, Rochester, MN; 2MD Anderson Cancer Center, Houston, TX; 3Roswell Park Comprehensive Cancer Center, Buffalo, NY; 4Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY; 5Banner MD Anderson Cancer Center, Scottsdale, AZ; 6Yale Univ. School of Med., New Haven, CT; 7The James Cancer Hospital Solove Research Institute and The Ohio State University Wexner Medical Center, Columbus, OH; 8Washington University School of Medicine in Saint Louis, St. Louis, MO; 9Texas Oncology Baylor Charles A. Sammons Cancer Center, Dallas, TX; 10University Hospitals Seidman Cancer Center, Cleveland, OH; 11University of Kansas Medical Center, Westwood, KS; 12Hematology/Oncology, Mayo Clinic, Jacksonville, FL; 13Division of Hematology and Oncology, Medical College of Wisconsin, Milwaukee, WI; 14University of Alabama at Birmingham, Birmingham, AL; 15University of Nebraska Medical Center, Omaha, NE; 16Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX; 17Ottawa Hospital, Ottawa, ON, CAN; 18Translational Science and Therapeutics Division, Fred Hutch Cancer Research Center, Seattle, WA; 19University of North Carolina, Chapel Hill, NC; 20Holden Comprehensive Cancer Center, University of Iowa Hospital and Clinics, Iowa City, IA; 21Division of Hematology and Oncology, Weill Cornell Medical College, New York, NY; 22Weill Cornell Medical College, New York, NY; 23Stony Brook University Cancer Center, Stony Brook, NY; 24Hans Messner Allogenic Transplant Program, Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, Canada; 25Weill Cornell Medical Center, New York, NY; 26Case Western Reserve University, Cleveland, OH; 27The Ottawa Hospital, University of Ottawa, Ottawa, Canada; 28Yale University School of Medicine, New Haven; 29The Ohio State University Wexner Medical Center, Columbus, OH; 30Actinium Pharmaceuticals, New York, NY; 31Fred Hutchinson Cancer Center, Clinical Research Division; University of Washington School of Medicine, Seattle, WA; 32Loxo Oncology at Lilly, Stamford, CT; 33Memorial Sloan Kettering Cancer Center, New York, NY; 34Washington University In St. Louis, Saint Louis, MO; 35Division of Hematology and Oncology, Loyola University Medical Center, Maywood, IL

Background

Most older patients with relapsed or refractory (R/R) AML cannot tolerate intensive treatment and are not eligible for curative allogeneic hematopoietic cell transplant (HCT).

131I-apamistamab, an anti-CD45 radioimmunoconjugate, delivers high dose targeted radiation to hematopoietic cells, allowing for myeloablation and eradication of leukemic cells.

131I-apamistamab-based novel induction/conditioning can provide these patients with access to HCT.

Objective

Here we report on the rates and distributions of durable complete remission (dCR) in patients who received 131I-apamistamab at varying dose levels.

Iomab-B: Iodine (131I) Apamistamab

131I-apamistamab, or Iomab-B, targets CD45, which is expressed on hematopoietic cells, including the majority of malignant myeloid and lymphoid cells. In this way, Iomab-B delivers targeted radiation directly to leukemic cells and avoids non-targeted tissue. Following a dosimetric dose and biodistribution assessment, patients receive a personalized therapeutic dose designed to deliver a maximum of 24 Gy to the liver or 48 Gy to the bone marrow, whichever results in a lower activity to be administered.

SIERRA was a controlled, optional one-way crossover study of Iomab-B versus Investigator's choice of salvage therapy in patients aged 55 years or older with active, R/R AML. Patients randomized to Conventional Care (CC) who achieved CR could proceed to allogeneic HCT or other standard treatment. Patients not achieving CR could crossover to receive Iomab-B.

SIERRA Iomab-B Treatment Schedule

Patient Characteristics

Conditioning and Transplant Characteristics

Of the evaluable patients treated with Iomab-B & HCT, 100% engrafted.

Delivered Dose vs. dCR Rate

Figure 1. Distribution of pts with durable complete remission (dCR) stratified by the ratio of marrow/liver absorbed radiation dose, with higher ratio indicating more favorable biodistribution.

• In patients who received liver doses of >22 Gy the rate of dCR was
  27.6% vs. 13.5% in patients with liver doses ≤22 Gy.

Distribution of Marrow and Liver Dose by dCR

Marrow Dose

Liver Dose

• The distribution of bone marrow and liver absorbed dose demonstrates a dose-response relationship with a higher dose to the liver and marrow observed in patients achieving dCR.
• In patients achieving dCR, median liver dose was 22.5 Gy vs.
• 1. Gy for patients not achieving dCR.
• In patients achieving dCR, median bone marrow dose was
• 1. Gy vs. 15.6 Gy for patients not achieving dCR.

Organ-Specific Dosimetry with Iomab-B

		Absorbed dose per unit		Total absorbed dose
Organ	administered activity
	(Gy)
		(cGy/mCi)
Bone marrow		2.60 (0.9 - 9.6)		16.0 (4.6	-	44.6)
Spleen		14.1 (2.7 - 34.5)		91.5 (30.3	-	159.2)
Liver		3.34 (1.4 - 6.1)		21.6 (12.8 - 24.5)
Heart		0.42 (0.2 - 1.0)		2.6 (1.5	-	6.5)
Lungs		0.40 (0.2 - 1.0)		2.5 (1.5 - 6.1)
Small intestine		0.39 (0.2 - 1.0)	2.4 (1.1	-	6.8)
Stomach wall		0.58 (0.3 - 1.1)	3.6 (2.0	-	8.2)
Kidneys		0.67 (0.4 - 1.2)		4.1 (2.5	-	8.2)
Preferred		0.52 (0.3 - 1.1)		3.3 (2.0 - 10.0)
Whole body
Grade ≥3 Treatment Emergent Adverse Events
		Administered Liver Dose		Administered Liver Dose
Adverse Event	≤ 22 Gy (N=37)		> 22 Gy (N=29)
		N (%)		N (%)
Febrile Neutropenia	17 (45.9)	10 (34.5)
(FN)
Sepsis	2 (5.4)	2 (6.9)
Mucositis1	5 (13.5)	5 (17.2)
Acute Kidney Injury	2 (3.4)	1 (2.1)
aGVHD	3 (8.1)	3 (10.3)
Venoocclusive liver	1 (2.7)	0 (0.0)
disease

1."Mucositis" includes the Preferred Terms "Mucosal Inflammation" and "Stomatitis"

Conclusions

• 131I-apamistamab led induction/conditioning followed by HCT resulted in statistically significant improvement in dCR at 6 months vs. conventional care.
• A dose response was demonstrated for patients receiving
  131I-apamistamab, with those receiving a liver dose closer to the MTD of 24 Gy having about twice the dCR rate compared to patients receiving 22 Gy (MTD -1) or less.
• Patients with higher marrow/liver ratio experienced considerably higher rate of dCR, highlighting the importance of maximizing the dose to target tissues within the limits of established risk organ

dose tolerances.

The SIERRA trial has completed enrollment (www.sierratrial.com or clinicaltrials.gov, NCT02665065)