Emerging Strategies Reshape Treatment Landscape for Diffuse Large B-Cell Lymphoma
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New research presented at the American Society of Hematology (ASH) Annual Meeting highlights a shift towards personalized medicine and novel assessment tools in the fight against diffuse large B-cell lymphoma (DLBCL), a common and aggressive cancer.
Diffuse large B-cell lymphoma (DLBCL) impacts thousands globally, and its treatment is undergoing a rapid evolution driven by advances in molecular profiling, immunotherapy, and response-adapted monitoring.At the 67th ASH Annual Meeting, held December 6 through 9 in orlando, Florida, leading experts discussed how these innovations are paving the way for the next generation of DLBCL care.
The session,titled “Now Is the Time to Improve Outcomes in Diffuse Large B-cell Lymphoma,” featured insights from Sarah rutherford,MD,of Weill Cornell Medicine; jennifer Crombie,MD,of Dana Farber Cancer institute; and Franck Morschhauser,PhD,of Center Hospitalier Universitaire de Lille,France. Presenters outlined a series of innovations designed to inform personalized treatment strategies, while also acknowledging the challenges inherent in implementing these new methods.
Earlier Response Assessment: A Key to Improved Outcomes
According to Jennifer Crombie, improving outcomes for DLBCL patients begins with earlier and more precise response assessments to guide therapy modifications. Her presentation focused on opportunities to enhance prognosis and early detection through the use of interim positron emission tomography (iPET) scans and the measurement of circulating tumor DNA (ctDNA) to detect minimal residual disease (MRD).
“Utilizing ctDNA could be particularly effective at identifying patients who may benefit from a treatment alteration,” Crombie stated.
Currently, many patients receive frontline chemotherapy, frequently enough a regimen of rituximab (Rituxan; Roche), cyclophosphamide (Cytoxan; bristol Myers Squibb), doxorubicin (Adriamycin; Pfizer), vincristine (vincristine sulfane injection; Pfizer), and prednisone (R-CHOP), or polatuzumab (Polivy; Genentech) combined with R-CHOP.While many experience critically important improvements,a PET scan at the end of treatment,or an iPET scan mid-treatment,is crucial for determining the cancer’s state and the treatment’s impact for those who don’t achieve a complete response.
However, Crombie cautioned that PET scans are not without limitations. She described a “high false-positive rate,” which can lead to unnecessary therapy changes in patients who are actually responding to treatment.Moreover, a 10-year follow-up of the PETAL trial (NCT00554164) demonstrated that while iPET could predict outcomes in aggressive lymphoma, altering treatment based on iPET results did not ultimately improve patient outcomes.
ctDNA: A More Promising Avenue for Personalized Treatment
Crombie highlighted molecular testing using ctDNA assessments as a more productive approach. She posed the question, “Can we do better?” and outlined several next-generation sequencing assays for MRD.
Franck Morschhauser advised caution when considering sequencing for CAR T-cell outcomes. He expressed a preference for CAR T-cell therapy in the second line, but suggested BsAbs may be more beneficial in the third line, following CAR T-cell therapy failure.Research led by Topp et al demonstrated the effectiveness of odronextamab, a BsAb, as monotherapy in patients with disease progression after CAR T-cell therapy.
“Patients experiencing disease progression after CAR T and bispecifics still have [significant] unmet need, and we should focus our research on those patients,” Morschhauser concluded.
