Subscribe

Subscribe Today!

To sign up for our newsletter or print publications, please enter your contact information below.

I'd like to receive:

Apamistamab-Based Lymphodepleting Regimen Before CAR T-Cell Therapy Prevents Cytokine Release Syndrome

JHOP - February 2020 Vol 10, No 1 - ASH Highlights, CAR T-Cell Therapy, Immunotherapy
Download pdf

A new CD45-targeting antibody radiation-conjugate, iodine-131 (I-131) apamistamab, may be a less toxic alternative to today’s standard practice of chemotherapy-based lymphodepletion regimens before initiation of adoptive cell therapy, according to results presented at ASH 2019.

The use of I-131 apamistamab before chimeric antigen receptor (CAR) T-cell therapy may enable lympho­depletion through a single-dose outpatient administration compared with chemotherapy-based lymphodepletion regimens that require multiple infusions in an inpatient setting over several days.

Adverse events associated with the current chemotherapy-based lymphodepletion regimen of fludarabine plus a cyclophosphamide include cytokine release syndrome and neurotoxicity.

“There is good rationale to use apamistamab before you infuse CAR T-cells. When you add the lymphocytes from the outside for a therapeutic reason, these lymphocytes grow much better if the host immune system lymphocytes have been depleted. At the same time, there is more toxicity from a CAR-T procedure if it is given with lymphodepletion,” said Rajneesh Nath, MD, hematology/medical oncology specialist, Banner M.D. Anderson Cancer Center, Gilbert, AZ.

“When we used a test dose of apamistamab to see the biodistribution of this drug, we noticed that the lymphocyte count in the blood was dropping. The lymphocyte count dropped enough so that this could be used as lympho­depleting chemotherapy. Lymphocytes remain depleted in the time frame when we need to infuse the CAR T-cells,” Dr Nath noted.

The SIERRA Study

In the pivotal phase 3 SIERRA clinical trial presented at the meeting, an 85% reduction in lymphocytes was observed at the postdosimetry infusion time point, a 67% decrease at day 1 post–dosimetric infusion, followed by a 43% decrease 1 week later, just before I-131 apamistamab therapeutic infusion, in patients with relapsed or refractory acute myeloid leukemia (AML) compared with pre–­dosimetric infusion, he said.

In addition to the 85% reduction in lymphocytes at the postdosimetry infusion, a 35% reduction in peripheral leukemic blasts was found at the postdosimetry infusion, suggesting a rapid antileukemic effect with single-agent I-131 apamistamab.

These data suggest that this method of lymphodepletion is specifically targeted to CD45-positive immune cells, which, according to Dr Nath and colleagues, could have an antitumor effect. Furthermore, they noted in their poster, it “can be administered in an outpatient setting.”

I-131 apamistamab targets CD45, an antigen expressed on the surface of many cells that are relevant to CAR T-cell therapy, including lymphocytes, macrophages, and regulatory T-cells. A preponderance of these cells has been associated with a lack of durable response to CAR T-cell therapy, as well as the adverse event of cytokine release syndrome and other neurologic events.

In the SIERRA study, before administration of a therapeutic dosage of I-131 apamistamab in patients with AML, dosimetry using a tracer amount of I-131 apamistamab was performed in the outpatient to calculate a patient-­specific therapeutic infusion dose.

Blood samples from 56 evaluable patients demonstrated a significant but transient reduction in lymphocytes and white blood cells compared with pre–dosimetry infusion levels, at approximately one-tenth of the targeted lymphodepletion dose of I-131 apamistamab.

There was no significant change in the levels of platelets, red blood cells, and neutrophils preinfusion versus postdosimetry infusion.

“Based on the clearance of iodine-131 apamistamab, an adoptive-cell therapy such as CAR T could be administered around 6 days postlymphodepletion, with a 75 mCi ­dosage,” said Dr Nath. Based on the SIERRA study, a nonmyeloablative dosage of 75 mCi has been proposed as a starting dose, in combination with a CAR T-cell therapy.

Related Items
Kymriah Received Accelerated FDA Approval for Relapsed or Refractory Follicular Lymphoma
JHOP - June 2022 Vol 12, No 3 published on June 16, 2022 in FDA Oncology Update, Lymphoma, CAR T-Cell Therapy
Yescarta First CAR T-Cell Therapy FDA Approved for Large B-Cell Lymphoma
JHOP - June 2022 Vol 12, No 3 published on June 16, 2022 in FDA Oncology Update, CAR T-Cell Therapy, Lymphoma
Opdualag, a Novel Immunotherapy Combination, FDA Approved for Advanced Melanoma
JHOP - April 2022 Vol 12, No 2 published on May 3, 2022 in FDA Oncology Update, Melanoma, Immunotherapy
Carvykti Second BCMA-Directed CAR T-Cell Therapy FDA Approved for Multiple Myeloma
JHOP - April 2022 Vol 12, No 2 published on May 3, 2022 in FDA Oncology Update, CAR T-Cell Therapy, Multiple Myeloma
Hepatitis B Virus Infection Monitoring in Patients with Lymphoma Receiving Anti-CD20 Monoclonal Antibodies
Christopher Sinoimeri, PharmD, Bryan Do, PharmD, BCOP, Sheree Chen, PharmD, BCOP
JHOP - April 2022 Vol 12, No 2 published on May 3, 2022 in Original Article, Lymphoma, Immunotherapy, Infections
Second-Line Axicabtagene Ciloleucel Therapy Improves Outcomes in Patients with Large B-Cell Lymphoma: ZUMA-7
Robert J. Ignoffo, PharmD, FASHP, FCSHP, FHOPA
JHOP - April 2022 Vol 12, No 2 published on May 3, 2022 in From the Literature, Lymphoma, CAR T-Cell Therapy
The Impact of a Comprehensive Immunotherapy Continuing Education Curriculum on Pharmacists’ Knowledge, Competence, and Confidence
JHOP - March 2022 Vol 12 Special Feature published on March 22, 2022 in HOPA Abstracts, Immunotherapy
A Review of CAR T-Cell Therapies Approved for the Treatment of Relapsed and Refractory B-Cell Lymphomas
Drew A. Wells, PharmD, BCPS, Jenna Summerlin, PharmD, Zachery Halford, PharmD, BCOP, BCPPS
JHOP - February 2022 Vol 12, No 1 published on March 1, 2022 in Review Article, CAR T-Cell Therapy, Lymphoma
Immune Responses to COVID-19 Vaccines Low Among Patients with Hematologic Malignancies, but mRNA Vaccines Induce Strong Antibody Response in AML and MDS
JHOP - February 2022 Vol 12, No 1 published on March 1, 2022 in ASH Highlights
A Paradigm Shift: CAR T-Cell Therapy Beats Standard of Care as Second-Line Treatment for Large B-Cell Lymphoma
JHOP - February 2022 Vol 12, No 1 published on March 1, 2022 in ASH Highlights
Copyright © The Lynx Group, LLC. All rights reserved.