Photo Credit: Nemes Laszlo
Mantle cell lymphoma (MCL) with TP53 mutation (TP53m) represents a significant therapeutic challenge, as this mutation predicts poor outcomes, including early disease progression and high mortality rates. Despite advancements in treatment, optimal strategies for patients with TP53m MCL remain unclear. To address this gap, a systematic review and meta-analysis was conducted to evaluate the effectiveness of various treatment modalities for patients with newly diagnosed and relapsed or refractory TP53m MCL. The findings were presented at the 2024 American Society of Hematology Annual Meeting.
The analysis included 28 studies encompassing targeted therapies, combination therapies, hematopoietic stem cell transplantation (HSCT), and chimeric antigen receptor T-cell (CAR-T) therapies. Outcomes measured included complete remission (CR) rates, overall response (OR) rates, and overall survival (OS). Among the findings, the pooled CR and OR rates for patients with TP53m MCL were 68% and 79%, respectively, across all treatment approaches.
For patients with newly diagnosed TP53m MCL, targeted therapies yielded the highest CR (79%) and OR (96%) rates, demonstrating significant efficacy. However, for those with relapsed or refractory disease, CAR-T therapy showed superior outcomes, with CR and OR rates reaching 84% and 95%, respectively. In terms of survival, the overall 1-year and 2-year OS rates for patients with TP53m MCL were 63% and 53%, respectively. Allogeneic HSCT offered a 1-year OS rate of 69% and a 2-year OS rate of 62% for newly diagnosed patients, and patients with relapsed or refractory disease saw modest improvements in 1-year OS (61%) and 2-year OS (44%) with CAR-T therapy.
Despite these advancements, survival rates remain suboptimal, especially for patients with relapsed or refractory disease, underscoring the aggressive nature of TP53m MCL. Although targeted therapies and CAR-T approaches demonstrate high response rates, their limited impact on long-term survival highlights the need for innovative treatment strategies.
“Although targeted therapy or CAR-T therapy can achieve an relatively high response rate for newly diagnosed or relapsed/refractory TP53m MCL patients, survival was still poor for these patients and more effective treatment strategies need to be exploded,” the authors noted.
Future research must focus on developing more effective therapeutic approaches to address the unmet needs of this high-risk population.
