Bfl-1 is a positive response biomarker for CDK9 inhibitor antitumor efficacy across DLBCL cell line and PDX tumors in vivo. (A-B) CB17 SCID mice were implanted with OCILY10 (A) or TMD8 (B) cells and xenograft tumors grew to ∼200 mm³ prior to treatment with AZD4573 or AZD5991. (C) Pharmacodynamic analysis of pSer2-RNAP2, cleaved caspase-3, and antiapoptotic Bcl-2 family proteins in OCILY10 xenograft tumors after 4 hours of AZD4573 treatment. Western blot loading control, GAPDH. (D) Western blot analysis of prosurvival Bcl-2 family protein levels across 8 DLBCL PDX tumor models. Loading control, GAPDH. (E-G) NOD SCID mice were implanted with LY6934 (E), LY2214 (F), or LY3604 (G) DLBCL patient-derived tumor cells and treated with either AZD4573 or AZD5991 for 3 dosing cycles. Left panels, antitumor drug responses throughout the entire study duration. Right panels, individual animal tumor volumes at the indicated day. **P < .01; ****P < .0001. ns, no significance.