Dimitra R. Bakaloudi: Evaluating TMB and MSI in patients with Urothelial cancer treated with ICIs

Dimitra R. Bakaloudi, Postdoctoral GU Oncology Researcher at University of Washington, shared on X about recent paper by her as first autor, titled “Association of Tumor Mutational Burden and Microsatellite Instability With Response and Outcomes in Patients With Urothelial Carcinoma Treated With Immune Checkpoint Inhibitor” published on Science Direct.

Authors: Dimitra Rafailia Bakaloudi, Rafee Talukder, Dimitrios Makrakis, Leonidas Diamantopoulos, Thomas Enright, Jacob B. Leary, Ubenthira Patgunarajah, Vinay M. Thomas, Umang Swami, Neeraj Agarwal, Tanya Jindal, Vadim S. Koshkin, Jason R. Brown, Pedro Barata, Jure Murgić, Marija Miletić, Jeffrey Johnson, Yousef Zakharia, Gavin Hui, Alexandra Drakaki, Ignacio Duran, Lucia A. Buznego, Rafael M. Barrera, David M. Castañeda, Macarena Rey-Cárdenas, Daniel Castellano, Charles B. Nguyen, Joseph J. Park, Ajjai Alva, Rana R. McKay, Tyler F. Stewart, Ilana B. Epstein, Joaquim Bellmunt, Jonathan L. Wright, Shilpa Gupta, Petros Grivas, Ali Raza Khaki.

“I am delighted to share our manuscript evaluating Tumor Mutational Burden (TMB) and Microsatellite Instability (MSI) in patients with Urothelial cancer treated with ICIs.

Thanks to our amazing team Petros Grivas, Ali Khaki, Rafee Talukder, Fred Hutchinson Cancer Center, University of Washington.

This work is a result of our multi-institutional database which includes >1700 pts with bladder cancer. We included adults with UC who received adjuvant ICI, 1L/upfront ICI, switch maintenance avelumab (mAV), or ≥ 2L ICI with available tissue TMB or MSI data.

1L upfront treatment: OS was numerically (without statistical significance) longer in patients with TMB ≥10 versus TMB <10 (mOS 35 vs. 26 months, HR = 0.6 [95% CI, 0.4-1.1]) and in patients with MSI-H (mOS NR) and MSI-S tumors (mOS 22 months), respectively.

2+L treatment: OS was not statistically different, though mOS was numerically longer in patients with TMB ≥10 versus TMB <10 (mOS 20 vs. 12 months, HR = 0.9 [95% CI, 0.4-1.7]) and in patients with MSI-S and MSI-H tumors, mOS 17 and 12 months, respectively.

maintenance avelumab: OS was statistically significantly longer in patients with TMB ≥10 vs patients with TMB <10 (61 vs. 17 months; HR = 0.2 [95% CI, 0.05-0.6], P = .006) and numerically longer in those with MSI-H (mOS NR) versus MSI-S (mOS 24 months).

We also found that patients with MSI-H tumors had higher ORR with ICI versus patients with MSI-S tumors in 1L/upfront setting. TMB and MSI analyses by therapy line are shown in the Table.

Main conclusions:

• Longer mOS in pts with TMB≥10 compared to TMB <10 and with MSI-H and MSI-S tumors after ICI; especially mAV
• Better response rates to ICI in pts with high TMB and MSI tumors compared to low TMB and MSI-S tumors especially in the 1L treatment.”

Source: Dimitra R. Bakaloudi/X