Ten-Year Outcomes after CAR T-Cell Therapy for B-Cell Lymphomas
After 10 years one third of the heavily pretreated lymphoma patients who had CAR-T therapy stayed disease free.
Remission Assessment by Circulating Tumor DNA in Large B-Cell Lymphoma
Author(s): Mark Roschewski, MD1; David M. Kurtz, MD, PhD2,3,4; Jason R. Westin, MD5; Ryan C. Lynch, MD6; Ajay K. Gopal, MD6; Stefan K. Alig, MD, PhD2,7; Brian J. Sworder, MD, PhD8; Hua-Jay J. Cherng, MD9; Christian Kuffer, PhD10; Derek Blair, PhD10; Krystal Brown, PhD4; Jordan S. Goldstein, MD2; Andre Schultz, PhD4; Sandra Close, PhD4; Jacob J. Chabon, PhD4; Maximilian Diehn, MD, PhD3,11,12; Wyndham H. Wilson, MD, PhD1; Ash A. Alizadeh, MD, PhD2,3,11;
Source: DOI: 10.1200/JCO-25-01534
Dr. Maen Hussein's Thoughts
Minimal residual disease (MRD) testing after two cycles of therapy and at the end of treatment predicted 2-year progression-free survival (PFS) (96% in MRD-negative patients vs 67% in MRD-positive patients). MRD status was more predictive of treatment outcomes than radiographic imaging in this patient population.
PURPOSE
Large B-cell lymphomas (LBCLs) are curable, but patients with residual disease after therapy invariably experience progression. Ultrasensitive methods to detect circulating tumor DNA (ctDNA) as minimal residual disease (MRD) may improve the determination of remission.
METHODS
We integrated data from five prospective studies of frontline anthracycline-based chemotherapy in patients with LBCL. Tumor-specific phased variants were identified from pretreatment samples and monitored landmark time points. Serial plasma specimens were blindly analyzed for detectable ctDNA as MRD. MRD status was compared with conventional response criteria for prognosis of progression-free survival (PFS).
RESULTS
We studied ctDNA-MRD in 137 patients by monitoring 409 plasma specimens over time. Detectable ctDNA rates decreased during therapy with 55% and 78% of patients achieving undetectable ctDNA after two cycles and the end of therapy, respectively. After a median follow-up of 37 months, the 2-year PFS for patients with detectable versus undetectable ctDNA after two cycles was 67% versus 96% (P = .0025; hazard ratio [HR], 6.9) and after therapy was 29% versus 97% (P < .0001; HR, 28.7), respectively. Ninety-two (94%) patients with undetectable ctDNA the end of therapy remained alive without progression, while 19 (68%) patients with detectable ctDNA progressed or died. MRD status the end of therapy had greater prognostic utility than conventional lymphoma response criteria using positron emission tomography (PET) scans (HR, 3.6 for positive PET and 28.3 for detectable ctDNA).
CONCLUSION
Ultrasensitive ctDNA detection after frontline LBCL therapy is more prognostic than conventional radiographic response criteria. A refined definition of remission with ctDNA-MRD may improve clinical and psychological outcomes for patients with LBCL.
Author Affiliations
1Lymphoid Malignancies Branch, National Cancer Institute, Bethesda, MD; 2Division of Oncology, Department of Medicine, Stanford University, Stanford, CA; 3Stanford Cancer Institute, Stanford University, Stanford, CA; 4Foresight Diagnostics, Boulder, CO; 5Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX; 6Division of Hematology Oncology, Department of Medicine, University of Washington School of Medicine Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA; 7Department of Hematology and Stem Cell Transplantation, University Hospital Essen, Essen, Germany; 8Division of Hematology Oncology, Department of Medicine, University of California, Irvine School of Medicine, Irvine, CA; 9Division of Hematology & Oncology, Columbia University Irving Medical Center, New York, NY; 10MorphoSys, a Novartis Company, Planegg, Germany; 11Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, CA; 12Department of Radiation Oncology, Stanford University, Stanford, CARelated Articles
Tafasitamab plus lenalidomide and R-CHOP versus R-CHOP for first-line treatment of patients with high-risk diffuse large B-cell lymphoma (frontMIND): a global, phase 3, randomised, double-blind, placebo-controlled trial
Progression-free survival was improved in the tafa-len-R-CHOP group vs the R-CHOP with 2-year progression-free survival rates of 71·1vs 62·9% toxicity was higher with tafa-len-R-CHOP with a higher rate of fatal treatment-emergent adverse events, but more overall deaths the RCHOP arm. It is early to add Len taf because of toxicity esp with OS survival and deep response data being immature.
Mosunetuzumab Plus Polatuzumab Vedotin in Transplant-Ineligible Refractory/Relapsed Large B-Cell Lymphoma: Primary Results of the Phase III SUNMO Trial
Median progression-free survival (PFS) was significantly longer with mosunetuzumab plus polatuzumab vedotin (Mosun-Pola) than with R-GemOx (11.5 months vs 3.8 months). The overall response rate (ORR) was significantly higher with Mosun-Pola compared with R-GemOx (70% vs 40%; P < .0001), with complete response rates of 51% and 24%, respectively. Cytokine release syndrome (CRS) occurred in fewer than 5% of patients.
Five-Year Outcomes of the POLARIX Study Comparing Pola-R-CHP and R-CHOP in Patients With Diffuse Large B-Cell Lymphoma
Another update demonstrated the superiority of polatuzumab vedotin plus R-CHOP (Pola-R-CHOP) over R-CHOP alone, with improved progression-free survival (PFS) (64% vs 59%). Overall survival (OS) was not statistically significant; however, the hazard ratio was 0.85, with greater benefit observed in high-risk patients.
Brentuximab Vedotin Combination for Relapsed Diffuse Large B-Cell Lymphoma
The ECHELON-3 study showed BV + Len + R is an active and (relatively) tolerable in the rrDLBCL patient group. Interestingly, patients did not have to be CD30+ to see a benefit.