68Ga-pentixafor PET/CT Indicates Inconsistent Response With Monoclonal Protein-based Response Criteria in Waldenström Macroglobulinemia/Lymphoplasmacytic Lymphoma Patients Treated With Bruton Tyrosine Kinase Inhibitors

Background Waldenström macroglobulinemia/lymphoplasmacytic lymphoma (WM/LPL) is a rare, indolent non-Hodgkin lymphoma. Bruton tyrosine kinase inhibitors (BTKis) have been widely used for the treatment of WM/LPL. The objective of this study is to evaluate the response assessed by 68 Ga-pentixafor PET/CT in patients with WM/LPL treated with either BTKi or chemoimmunotherapy. Patients and Methods: This is a post hoc analysis of the data from our prospective cohort study. A total of 33 patients with newly diagnosed or relapsed WM/LPL were included. The clinical response was assessed using the International Workshop of WM (IWWM) response criteria based on the change of monoclonal protein level. 68 Ga-pentixafor PET/CT response was evaluated both visually and semiquantitatively. The total lesion uptake (TLU), metabolic tumor volume (MTV), and SUVmax were measured for semiquantitative assessments and were calculated as percentage change from baseline to follow-up scans (∆TLU%, ∆MTV%, ∆SUVmax%). The change of M-protein (∆M-pro%) and IgM (∆IgM%) was also calculated. Results: Among the included patients, 15 received chemoimmunotherapy (chemo-group), while 18 patients were treated with BTKi-containing regimens (BTKi group). In PET/CT visual assessment, 14/15 (93.3%) patients in chemo-group exhibited consistent response, as assessed by 68 Ga-pentixafor PET/CT and M-protein-based IWWM criteria. However, the PET/CT-based response was inconsistent with the IWWM response in 10/18 (55.6%) patients in the BTKi group. For semiquantitative analysis, ∆TLU%, ∆MTV%, and ∆SUVmax% in chemo-group showed a strong correlation with clinical response, ∆M-pro%, and ∆IgM% values (r = 0.634–0.856, P < 0.05). However, there was no statistically significant correlation between the changes in M-protein percentage or IgM percentage and the uptake values measured by 68 Ga-pentixafor PET/CT in BTKi group ( P > 0.05). Conclusions: 68 Ga-pentixafor PET/CT provides accurate response assessment in WM/LPL patients receiving chemoimmunotherapy. However, the 68 Ga-pentixafor PET/CT-based response exhibited inconsistency with the M-protein-based IWWM criteria in those treated with BTKis, thereby suggesting the potential inadequacy of the IWWM response criteria in WM/LPL patients treated with BTKis.