Nirav N. Shah, MD, on DLBCL: New Data on Split-Dose R-CHOP for Older Patients
2023 ASCO Annual Meeting
Nirav N. Shah, MD, of the Medical College of Wisconsin, discusses phase II results showing that split-dose R-CHOP offers older patients with diffuse large B-cell lymphoma (DLBCL) an equivalent dose intensity as R-CHOP-21 through a fractionated dosing schedule, improving tolerability. At the end of treatment for these older patients, a complete response rate of 71% was comparable to outcomes with R-CHOP in younger patients with the disease (Abstract 7554).
Disclaimer: This video transcript has not been proofread or edited and may contain errors.
The optimal management of older patients with DLBCL remains unclear and is very variable from practice to practice. The most commonly used regimen for older patients with diffuse large B-cell lymphoma is a regimen called R-mini-CHOP, which is more or less a 50% dose reduction in the cumulative chemotherapy compared to a younger patient who gets R-CHOP21. At our institution, we have developed a regimen called split-dose R-CHOP, which basically fractionates R-CHOP21 into two half doses with full-dose rituximab given on day one, and a 50% dose reduction of the CHOP regimen on day one and day 15, so that a 28-day cycle of split-dose R-CHOP gave the same chemo cumulative dose of chemotherapy as R-CHOP21. We designed this study as a way to deliver the same dose intensity to older patients, but by fractionating it, making it more tolerable to a patient population that's at higher risk of the toxicities associated with chemotherapy.
In addition, because older patients could benefit from a truncated chemotherapy regimen, we included an interim analysis of patients, where we looked at them using PET-CT and MRD, using a cell-free DNA assay-
... to look at the depth of response after two months of split-dose R-CHOP. For those patients who are both MRD-negative and, by Deauville criteria, a PET score of one, two, or three, those patients were then offered an abbreviated chemotherapy arm where they would finish after four months of split-dose R-CHOP instead of six months. Here, we are presenting our interim feasibility endpoint, which was based on the end-of-treatment CR rate. We're reporting data on 14 patients who have completed treatment, and our end-of-CR rate with 71%, meeting our interim feasibility endpoint early with 10 of the 14 patients achieving a complete remission.
Overall, this regimen was well-tolerated. There were adverse events as described in the data that we've shown, but some of these are to be expected treating an older patient population, but there were no treatment-related deaths directly related to the chemotherapy. The most interesting aspect of this data was, however, that analysis we did using PET-CT and MRD. For six patients, who were both MRD-negative and PET-CT-negative, five of the six went onto the abbreviated arm. Even though they finished this truncated regimen, all of them remained in remission to-date. This shows that there might be power in this early-responding group that have a high in-depth-
... response of this early interim analysis. We look forward to sharing this data at ASCO, and continuing to enroll patients, but we think that this could become a paradigm on how to treat older patients with DLBCL using novel endpoints, while offering a regimen with the same dose intensity that we offer younger patients to improve efficacy.
Carmen E. Guerra, MD, MSCE, of the University of Pennsylvania Abramson Cancer Center, discusses three key abstracts presented at ASCO: strategies to increase accrual of underrepresented populations in Alliance NCTN trials, how patient-clinician education can strengthen partnerships and improve diversity in breast and lung cancer trials, and mediators of racial and ethnic inequities in clinical trial participation among U.S. patients with cancer from 2011 to 2022 (Abstracts 6509, 6510, 6511).
Alicia K. Morgans, MD, MPH, of Dana-Farber Cancer Institute, and Karim Fizazi, MD, of Institut Gustave Roussy, University of Paris-Saclay, discuss findings from the TALAPRO-2 study, which showed that talazoparib plus enzalutamide improved radiographic progression–free survival over standard-of-care enzalutamide as first-line treatment for patients with metastatic castration-resistant prostate cancer and HRR gene alterations. This regimen also delayed the time to deterioration in global health status and quality of life (Abstract 5004).
Amer Methqal Zeidan, MBBS, MHS, of Yale University and Yale Cancer Center, discusses phase III findings on the first-in-class telomerase inhibitor imetelstat, which was given to patients with heavily transfusion-dependent non-del(5q) lower-risk myelodysplastic syndromes that are resistant to erythropoiesis-stimulating agents. Imetelstat resulted in a significant and sustained red blood cell (RBC) transfusion independence in 40% of these heavily transfused patients. The response was also durable and accompanied by an impressive median hemoglobin rise of 3.6 g/dL, and seen in patients with and without ring sideroblasts. Importantly, reduced variant allele frequency was observed in the most commonly mutated myeloid genes which correlated with duration of transfusion independence and hemoglobin rise, therefore suggesting a disease-modifying potential of this agent (Abstract 7004).
Funda Meric-Bernstam, MD, of The University of Texas MD Anderson Cancer Center, discusses interim results from the DESTINY-PanTumor02 trial, the first tumor-agnostic global study of fam-trastuzumab deruxtecan-nxki (T-DXd) in a broad range of HER2-expressing solid tumors. This agent showed an encouraging overall response rate, particularly in patients with IHC 3+ expression; durable clinical benefit; and a manageable safety profile in these heavily pretreated patients. T-DXd may be a potential new treatment option for this population (Abstract LBA3000).
Narjust Florez, MD, of Dana-Farber Cancer Institute, and Heather A. Wakelee, MD, of Stanford University, Stanford Cancer Institute, discuss new data supporting neoadjuvant pembrolizumab plus chemotherapy followed by surgery and adjuvant pembrolizumab as a promising new treatment option for patients with resectable stage II, IIIA, or IIIB (N2) non–small cell lung cancer (NSCLC) (Abstract LBA100).