Along with PET, ctDNA offers novel benefits in identifying genetic subgroups and guiding treatment adjustments to assess acalabrutinib’s role in non-chemotherapy responders.
Circulating tumor DNA is gaining ground as an important multitasking tool in the frontline treatment of diffuse large B-cell lymphoma , with key novel applications that include identifying genetic subtypes and guiding the escalation or de-escalation of chemotherapy, new research has shown.
“We have demonstrated that a PET/ctDNA-guided approach in frontline DLBCL is feasible in a multicenter setting,” said first author Anastasios Stathis, MD, of the Clinic of Hematology, Oncology Institute of Southern Switzerland, EOC, Bellinzona, Switzerland, in presenting the findings at the “The allocation of patients and treatment based on the combined results of PET and ctDNA is operationally successful,” he said. The findings are from the preliminary results of the phase 2 SAKK 38/19 trial, which focuses on the goal of identifying patients with key MCD genetic subtypes that are known to respond poorly to the standard of care of R-CHOP chemotherapy, and who may be more successfully treated with the addition of a Bruton tyrosine kinase inhibitor such as acalabrutinib. “The most important aspect of this study is the novelty of using ctDNA as a tool to identify a genetic subtype of DLBCL prior to treatment for the purpose of treating that cohort differently precision medicine,” said Mark Roschewski, MD, a senior clinician with the Center for Cancer Research, National Institutes of Health in Bethesda, Maryland, who was a discussant for the study, in comments toImportantly, there are currently no diagnostic assays available to identify the genetic details of a tumor in DLBCL prior to therapy, which can be so crucial in determining a treatment plan, Roschewski explained. “We know a lot about the complexity of DLBCL genetics, but the information is not actionable because it is such a challenge to get that information prior to therapy,” he said. “As such, this information is only available after therapy is over and mostly only reported in clinical trials.” For the study, conducted at 16 sites in Switzerland and 3 in Italy, the authors were able to utilize ctDNA to identify patients with the MCD subtype because of its ability to detect the two mutations known to be present in MCD:Among 230 treatment-naive patients with CD20-positive DLBCL screened for the trial, 194 patients had detectable ctDNA, and 35 had theImportantly, the turnaround time for the genetic profiling with ctDNA results among 124 patients in the full analysis set was only 9 days, and the median time to start treatment was just 15 days.Overall, in the full analysis set, 72.6% of patients had advanced disease , and 64.5% had extra-nodal involvement. With 96 patients excluded due to screening failure, 124 patients were included in the full analysis, and all that were found to havemutations were assigned to receive frontline therapy with acalabrutinib plus six cycles of R-CHOP in a group allocated as cohort A.Of the remaining 97 patients who did not have the mutations, all were started on two cycles of R-CHOP and then evaluated with ctDNA and PET to guide treatment escalation or de-escalation on the basis of one of three treatment strategies corresponding to their ctDNA/PET results. Overall, 6.5% of patients were found to be PET and ctDNA-positive after the two cycles and were therefore allocated to escalation of therapy to four more R-CHOP cycles plus acalabrutinib, followed by 2 months of acalabrutinib . About 30.6% of patients were ctDNA and PET-negative and therefore had their therapy de-escalated, receiving only two more R-CHOP cycles plus two rituximab doses . About 36.5% of patients were either PET or ctDNA-positive after the two cycles and were allocated to receive four more R-CHOP cycles .Preliminary results including PET and ctDNA responses show that at the end of therapy, the majority of patients remained ctDNA-negative , with 7.3% ctDNA-positive and data missing on 12.9% of patients. Having detectable ctDNA at baseline significantly correlated with factors including the International Prognostic Index , bulky disease, and PET imaging parameters that indicated a poorer prognosis, including higher metabolic tumor volume and total lesion glycolysis . While the numbers were small, higher PET scores at the end of treatment correlated with ctDNA positivity, with the ctDNA positivity rate of only 2.6% among 78 patients with lower Deauville scores of 1-3. Notably, ctDNA negativity at the end of two cycles of R-CHOP showed only a nonsignificant trend in being associated with end-of-treatment negative PET scores. The only factors found to be predictors of positive PET imaging at the end of treatment included high baseline MTV and TLG (Further commenting on the study during his discussion at the meeting, Roschewski agreed that the discrepancies with ctDNA and PET scan results were a limitation. “We need to have more information on to understand why was there such a discordance in things that we typically think go in the same direction,” he said. However, “the quantitative level of baseline ctDNA in the study correlated quite nicely with tumor burden as measured by PET scan high-risk features such as IPI.” “But using it in a more nuanced way, this also was one of the first trials that showed us that you could actually risk stratify the patients based on the mutation profiling from ctDNA, and that was successful in 88% of the patients, and the turnaround time was only 9 days.” Roschewski noted that key additional studies are also looking at the addition of acalabrutinib to R-CHOP through different trial designs, including the ESCALADE trial, and a study Roschewski and his own team are also conducting looking at molecular profiles of patients who do and do not respond to acalabrutinib. Ultimately, “the main barrier to precision medicine in large lymphoma remains genetic heterogeneity, and we need to continue to find novel ways to overcome that barrier,” he said. Stathis disclosed ties with AbbVie, ADC Therapeutics, Amgen, AstraZeneca, Bayer, BMS, Cellista, Debiopharm, Incyte, Loxo Oncology, MSD, Novartis, Pfizer, Philogen, Prelude Therapeutics, and Roche. Roschewski reported having no disclosures.Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see ourPrimary Care Internal Medicine Is Dead
Genomic Medicine Positron Emission Tomography PET PET Scan Positron Emission Tomography (PET) Diffuse Large Cell Lymphoma DLBCL Diffuse Large B-Cell Lymphoma Diffuse Large B-Cell Lymphoma (DLBCL) Non-Hodgkin' S Lymphoma Non-Hodgkin Lymphoma NHL Non-Hodgkin Lymphoma (NHL) Genetics Biologic Therapy Biologics Lymphoma Malignant Lymphoma B-Cell Lymphoma
United States Latest News, United States Headlines
Similar News:You can also read news stories similar to this one that we have collected from other news sources.
Guide Helps Assess Child Abuse–Related Head InjuryThe Canadian Paediatric Society has published a Practice Point to help healthcare professionals assess traumatic head injury related to child maltreatment.
Read more »
Cannabis helps many women relax during sex, which helps them climax.A recent study shows that women who use cannabis shortly before partner sex have an easier time working up to orgasm.
Read more »
Apple explains how iPadOS 26 turns iPads into Mac-like multitasking marvelsWith a similar design language for iOS, iPadOS, & macOS, Apple is finally unlocking the iPad's true potential by offering real multitasking.
Read more »
Meta shows off two big AI upgrades – one helps robots, the other helps youTsveta, a passionate technology enthusiast and accomplished playwright, combines her love for mobile technologies and writing to explore and reveal the transformative power of tech.
Read more »
Apple Explains Why It Took So Long to Bring Desktop-Style Multitasking to iPadApple's Senior Vice President of Software Engineering, Craig Federighi, explains the reasons behind the late implementation of desktop-style multitasking on the iPad. The new feature, introduced in iPadOS 26, brings overlapping windows, a visible menu bar, and better support for background tasks. Federighi acknowledges that the interface may seem obvious now but highlights the previous limitations of iPad hardware and software.
Read more »
Can Tumor Patterns Predict Lymphoma Treatment Success?Novel lymphoma microenvironment profiles presage response to CAR T-cell therapy in large B-cell lymphoma.
Read more »