Main Session
Sep
29
SS 17 - Hem 1: Bridging the Gap: Radiotherapy Innovations in Aggressive Lymphomas
200 - TP53 Mutations and Outcomes after Radiotherapy in Mantle Cell Lymphoma
Presenter(s)
Alok Deshane, MD - MSKCC, New York, NY
A. Deshane1, B. S. Imber1, A. Wijetunga2, B. Fregonese1, A. Zelenetz3, G. Salles3, A. Kumar3, and J. Yahalom1; 1Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, 2University of North Carolina at Chapel Hill, Chapel Hill, NC, 3Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
Purpose/Objective(s):
The role for radiotherapy (RT) in mantle cell lymphoma (MCL) is limited as MCL often presents in advanced stages. A broader role may be rational given MCL’s propensity for profound but inconsistent radiosensitivity. Common molecular alterations in MCL impact prognosis, namely TP53 mutations (TP53mut). TP53mut can influence systemic therapy choices but its impact on radiosensitivity, or RT decision making is unclear. Better understanding could guide precision radiotherapy.Materials/Methods:
We analyzed patients (pts) treated with RT for MCL from 2010-2024, focusing on a cohort with next generation sequencing (NGS) for somatic genetic alterations (n=66). Age and stage at RT, treatment intent, relapsed status, site of RT, and prior systemic therapy were collected. Sites treated in pts with TP53mut vs without TP53mut (TP53WT) were compared. Lesion SUV and diameter, extranodal (EN) status of the treated site, blastoid histology, RT dose, and metabolic response at first assessment were compared. Additionally, sites receiving very low dose radiotherapy (VLDRT, 4 Gy) and sites of local failure (LF) were analyzed. Freedom from local progression (FFLP) was compared using log rank testing.Results:
66 patients were identified, treated to 97 sites. 84 sites (87%) were treated in the relapsed setting. 54 sites (56%) were localized relapsed or early-stage disease. By site, median follow up after RT was 1.5 years. 59 sites were of pts with blastoid histology. 61 sites (64%) treated were EN. Median RT dose was 30 Gy (4-40 Gy), median lesion diameter was 3.5 cm (0.9 - 22 cm), and median SUV max was 7.5 (0 - 61.6). 80% (n=77) of sites had available PET response assessment at a median of 1.7 months (0.1 - 7.1) post-RT. Overall response rate (ORR) was 98.7%, and complete response (CR) rate was 81% (n=62). 32% of pts (n=21) treated to 33 sites (34%) harbored TP53mut. RT dose (p =0.817) and CR% (p=0.491) did not differ significantly by TP53 status. When analyzed by site, TP53mut had significantly worse 1-year FFLP than TP53WT (85% vs 100% ; p=0.002). 6 sites overall (6.2%) had LF; of note, 4 of 6 sites received only 4 Gy. TP53mut status was associated with higher risk of LF (p= 0.024). Analysis of sites treated to 4 Gy (n=14; 14.4%) revealed that TP53mut remained associated with increased risk of LF (p=0.002). However, for sites receiving >4 Gy (n= 83; Median dose 30 Gy, Range 10-40 Gy), presence of TP53mut (n=30) was not significantly associated with FFLP (p=0.069).Conclusion:
In this cohort of MCL treated with RT, response was excellent, and LF was rare. Most sites of LF received VLDRT. TP53mut was significantly associated with higher risk of LF in sites treated with 4 Gy. Despite excellent responses to RT at higher, definitive doses, sites of pts with TP53mut might respond less favorably to VLDRT, suggesting relative radioresistance and the need to consider dose escalation or combination therapy strategies.