Abstract A119: Weight and muscle increase associated with neoadjuvant IL-1β and PD-1 blockade plus combination chemotherapy
Peter Yu, Matthew Wu, Michael Cross, Kohki Oyama, Akiko Sagara, Jimin Min, Manuel Hidalgo, Ammar Javed, Denis Guttridge, Dafna Bar-Sagi, Greg Sacks, Chenchan Huang, Paul ObersteinAbstract
Introduction:
The pro-inflammatory cytokine IL-1β is strongly associated with cachexia, so we explored changes in cachexia endpoints in patients receiving neoadjuvant IL-1β blockade along with PD-1 blockade and combination chemotherapy.
Methods:
Patients with resectable or borderline resectable pancreatic ductal adenocarcinoma (PDAC, n = 9) were treated with canakinumab, a high-affinity monoclonal human anti-interleukin-1 β (IL-1β) antibody, the PD-1 blocking antibody tislelizumab, and gemcitabine/nab-paclitaxel (gem/nab-pac). Patient weight was examined at baseline and after 4 months of therapy. Body composition segmentation was performed at the third lumbar vertebral level (L3) using contrast-enhanced computed tomography (CT) examinations acquired in the portal venous phase at baseline and after 4 months of therapy. A separate cohort of patients with PDAC receiving standard-of-care (SOC) neoadjuvant combination chemotherapy (n=22) were also examined as historical control and weight change after 4 months of therapy was analyzed.
Results:
5 out of 9 patients (56%) increased weight >2% after 4 months of canakinumab, tislelizumab, and gem/nab-pac therapy. The median absolute weight change was 2.4 kg, median relative weight change was 4% increase. From evaluable patients (n=6), total muscle area at L3 increased, median relative increase of 9.7%. Psoas and paravertebral muscle area also increased. Changes in subcutaneous adipose tissue area and muscle density did not have clear patterns. Using simple linear regression analysis, patient weight increase correlated with total muscle area increase (R2 = 0.94, p < 0.01). In patients receiving SOC neoadjuvant chemotherapy, 2 out of 22 patients (9%) increased weight >2% after 4 months of therapy. The patients receiving neoadjuvant canakinumab, tislelizumab, and gem/nab-pac had 6 times the relative risk of weight gain compared to historical control of patients receiving SOC chemotherapy (RR 6.1, 95% CI 1.6 – 24.9; Fisher’s exact p < 0.05).
Conclusions:
We report an exploratory observation of weight and muscle increase associated with neoadjuvant blockade of IL-1β and PD-1 plus combination chemotherapy, potentially anti-cachectic. While the primary analysis was for the 9 patients in the study, the number of patients achieving weight gain was statistically higher than with a historical control of patients receiving SOC chemotherapy.
Citation Format:
Peter Yu, Matthew Wu, Michael Cross, Kohki Oyama, Akiko Sagara, Jimin Min, Manuel Hidalgo, Ammar Javed, Denis Guttridge, Dafna Bar-Sagi, Greg Sacks, Chenchan Huang, Paul Oberstein. Weight and muscle increase associated with neoadjuvant IL-1β and PD-1 blockade plus combination chemotherapy [abstract]. In: Proceedings of the AACR Conference on Pancreatic Cancer: New Frontiers in Biology and Therapeutic Development; 2026 Sep 25-28; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(18_Suppl_2):Abstract nr A119.