ABSTRACT
In patients with locally advanced cancer without distant metastases, the neoadjuvant setting presents a platform to evaluate new drugs. For mismatch repair proficient/microsatellite stable (pMMR/MSS) colon and rectal cancer, immunotherapy has shown limited efficacy. Herein, we report exceptional responses observed with neoadjuvant botensilimab (BOT), an Fc-enhanced next-generation anti-CTLA-4 antibody, alongside balstilimab (BAL; an anti-PD-1 antibody) in two patients with pMMR/MSS colon and rectal cancer. The histological pattern of rapid immune response observed ("inside-out" (serosa-to-mucosa) tumor regression) has not been described previously in this setting. Spatial biology analyses (RareCyte Inc.) reveal mechanisms of actions of BOT, a novel innate-adaptive immune activator. These observations have downstream implications for clinical trial designs using neoadjuvant immunotherapy and potentially sparing patients chemotherapy.
Subject(s)
Colorectal Neoplasms , Rectal Neoplasms , Humans , DNA Mismatch Repair , Neoadjuvant Therapy , Antibodies, Monoclonal, Humanized/therapeutic use , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/geneticsABSTRACT
We conducted a retrospective record review to determine the frequency of venous thromboembolism (VTE) in patients with diffuse large B-cell lymphoma (DLBCL). All records from 1990 to 2001 of patients with the diagnosis of DLBCL at a tertiary care hospital were reviewed. Those with transformation from low-grade lymphoma, central nervous system lymphoma, HIV-related lymphoma or with incomplete records were excluded. All episodes of symptomatic VTE confirmed by imaging studies that were either present at diagnosis or occurred during initial treatment were identified. VTE occurred in 27 of 211 patients (12.8%). Stage I disease was associated with a low risk, whereas a high international prognostic index score increased risk. Of patients with VTE, thrombosis was present at diagnosis in 37% and occurred during the first chemotherapy cycle in 22% and during the first three cycles in 82%. The median survival of patients with VTE was 1.04 years [95% confidence interval (CI) = 0.75 - 1.33] compared to 5.2 years (95% CI 1.8 - 8.6) for those without VTE (P = 0.038). We conclude that VTE is a frequent complication of DLBCL that occurs particularly at diagnosis and during initial therapy, and it is associated with a worse prognosis.
