Three-drug regimen may reduce relapse risk after transplant for T-cell malignancies
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Adding romidepsin to busulfan and fludarabine reduced incidence of relapse among patients receiving allogeneic stem cell transplant for aggressive T-cell malignancies, according to results of a phase 1/phase 2 study.
The three-drug combination also mitigated the poor outcomes of patients with measurable residual disease prior to transplant, with toxicities similar to busulfan and fludarabine alone, initial findings presented at ASH Annual Meeting and Exposition showed.
“Unlike patients with B-cell malignancies, those with T-cell malignancies have very limited therapies, particularly in the relapsed/refractory setting outside of stem cell transplantation. Further, no trial has even been done specifically using allogeneic stem cell transplant for T-cell malignancies” Jonathan E. Brammer, MD, associate professor in the division of hematology at The Ohio State University Comprehensive Cancer Center, told Healio.
Background and methodology
Preclinical data showed enhanced and synergistic cell killing with the addition of romidepsin (Istodax, Bristol Myers Squibb), a histone deacetylase inhibitor, to busulfan and fludarabine in malignant T cells. Brammer and colleagues hypothesized the triplet regimen, along with romidepsin maintenance therapy, would enhance malignant T-cell killing, eradicate measurable residual disease at transplant, reduce relapse and induce the graft-versus-leukemia effect by stimulating natural killer cells.
“We designed this trial to decrease relapse in patients receiving allogeneic stem cell transplant for T-cell malignancies,” Brammer said.
The analysis included 21 patients aged younger than 70 years with a matched sibling/unrelated donor and a diagnosis of T-cell leukemia (including T-cell acute lymphoblastic leukemia) or T-cell lymphoma (cutaneous or peripheral) in at least a partial remission requiring an allogeneic stem cell transplant.
Patients received romidepsin, in addition to standard conditioning chemotherapy agents busulfan and fludarabine, and a maintenance dose of romidepsin every 2 weeks for 1 year after stem cell transplant to decrease the chance of a relapse while their immune system regained strength.
Determining the recommended phase 2 dose of romidepsin from three dose levels when combined with busulfan and fludarabine served as the primary objective.
Key findings
Researchers established the recommended phase 2 dose of romidepsin in conditioning as 2 mg/m2.
Initial results showed 88% of patients remained in remission 1 year after treatment completion, a dramatic increase in RFS compared with the expected rate of 45%, according to the press release from The Ohio State University Comprehensive Cancer Center.
Median OS had not yet been reached at median follow-up of 10.1 months, and median PFS was 28.2 months, the abstract stated.
Early data suggested maintenance romidepsin enhances natural killer cell cytotoxicity after allogeneic transplantation, potentially augmenting the graft-versus-leukemia effect and accounting for decreased relapse rates, the researchers wrote.
“The regimen decreased relapse rates to a greater extent than we had anticipated,” Brammer said.
Brammer said the treatment occurs during a critical time when the patient’s immune system is rebuilding strength to stop abnormal cell growth.
“Romidepsin maintenance after transplant stimulates natural killer-cell cytotoxicity (function),” he told Healio.
Continuing research
Long-term follow-up is needed to evaluate the results, the researchers wrote.
“We will further investigate how and why romidepsin increases natural killer-cell cytotoxicity after transplant,” Brammer said. “Further, we will continue to design and develop novel maintenance trials after allogeneic transplant for T-cell malignancies, as this is an important unmet need.”
References:
Hosing C, et al. Abstract 553. Presented at: ASH Annual Meeting and Exposition. Dec. 11-14, 2021; Atlanta.
New three-drug combo stimulates ‘master cancer killer’ cells, boosts immune system of patients undergoing stem cell transplantation. https://cancer.osu.edu/news/new-three-drug-combo-stimulates-master-cancer-killer-cells-boosts-immune-system-of-patients-undergoing-stem-cell-transplantation. Published Jan. 3, 2022. Accessed Jan. 14, 2022.
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Hosing C, et al. Abstract 553. Presented at: ASH Annual Meeting and Exposition; Dec. 11-14, 2021; Atlanta.
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