Investigators have uncovered how a specific sequence of cancer therapies could improve outcomes among patients with relapsed/refractory mature T- and natural killer (NK)-cell lymphomas, according to a recent study published by Sorial et al in the British Journal of Haematology.
Background
Relapsed/refractory T- and NK-cell lymphomas are aggressive hematologic malignancies that are often resistant to front-line therapies, thereby making them challenging to treat. Patients with these cancer types have poor prognoses.
There is currently no established treatment protocol for relapsed/refractory T- and NK-cell lymphomas. As a result, physicians must select the most appropriate second-line treatment options, including cytotoxic chemotherapies, epigenetic modifiers, and small-molecule inhibitors—without clear evidence to guide their decision-making.
Study Methods and Results
In the retrospective sequential treatment cohort study, the investigators examined data from the Peripheral T-Cell Lymphoma (PETAL) Consortium, involving patients who received upfront cytotoxic chemotherapy. They then categorized the patients based on who received second- and third-line treatments, including additional chemotherapy, epigenetic modifiers, or small-molecule inhibitors. The investigators analyzed overall survival across the treatment groups and compared 12 possible treatment strategies for second- and third-line therapies. They noted that 540 and 290 patients received second- and third-line therapies, respectively.
The investigators found that the patients had improved survival rates when treated with small-molecule inhibitors as second-line therapy followed by epigenetic modifiers as third-line therapy compared with those who were treated with other sequences. The survival benefits were especially pronounced among high-risk groups and patients with angioimmunoblastic T-cell lymphoma.
“Our robust study design, multiple stability analyses, and independent machine learning models using the PETAL global data set, all pointed to the same conclusion: targeted therapies and epigenetic modifiers consistently showed benefit over chemotherapy [among] patients with relapsed/refractory T- [and] NK-cell lymphomas,” indicated lead study author Mark Sorial, PharmD, BCOP, a researcher at the Mass General Cancer Center and a member of the Mass General Brigham health-care system.
Conclusions
“These results support the earlier use of these novel therapies, prioritize further research of these drug classes, and provide a framework for examining survival effects with sequential treatments in other cancers,” Dr. Sorial underscored. “They also highlight that targeted signaling inhibitors like duvelisib warrant ongoing clinical investigation in this patient population with limited treatment options,” he concluded.
Disclosure: The research in this study was funded in part by Secura Bio, Daiichi Sankyo, Kyowa Kirin, Acrotech Biopharma, and the Center for Lymphoma Research Funds as well as the National Cancer Institute K08 Career Development Award, MGH Lymphoma Research Funds, and the Reid Family Fund for Lymphoma Research. For full disclosures of the study authors, visit onlinelibrary.wiley.com.
