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Assessment of the Efficacy of Therapies Following Venetoclax Discontinuation in CLL Reveals BTK Inhibition as an Effective Strategy.
- Mato, Anthony R;
- Roeker, Lindsey E;
- Jacobs, Ryan;
- Hill, Brian T;
- Lamanna, Nicole;
- Brander, Danielle;
- Shadman, Mazyar;
- Ujjani, Chaitra S;
- Yazdy, Maryam Sarraf;
- Perini, Guilherme Fleury;
- Pinilla-Ibarz, Javier A;
- Barrientos, Jacqueline;
- Skarbnik, Alan P;
- Torka, Pallawi;
- Pu, Jeffrey J;
- Pagel, John M;
- Gohil, Satyen;
- Fakhri, Bita;
- Choi, Michael;
- Coombs, Catherine C;
- Rhodes, Joanna;
- Barr, Paul M;
- Portell, Craig A;
- Parry, Helen;
- Garcia, Christine A;
- Whitaker, Kate J;
- Winter, Allison M;
- Sitlinger, Andrea;
- Khajavian, Sirin;
- Grajales-Cruz, Ariel F;
- Isaac, Krista M;
- Shah, Pratik;
- Akhtar, Othman S;
- Pocock, Rachael;
- Lam, Kentson;
- Voorhees, Timothy J;
- Schuster, Stephen J;
- Rodgers, Thomas D;
- Fox, Christopher P;
- Martinez-Calle, Nicolas;
- Munir, Talha;
- Bhavsar, Erica B;
- Bailey, Neil;
- Lee, Jason C;
- Weissbrot, Hanna B;
- Nabhan, Chadi;
- Goodfriend, Julie M;
- King, Amber C;
- Zelenetz, Andrew D;
- Dorsey, Colleen;
- Bigelow, Kayla;
- Cheson, Bruce D;
- Allan, John N;
- Eyre, Toby A
Published Web Location
https://doi.org/10.1158/1078-0432.ccr-19-3815Abstract
Purpose
Venetoclax-based therapy is a standard-of-care option in first-line and relapsed/refractory chronic lymphocytic leukemia (CLL). Patient management following venetoclax discontinuation remains nonstandard and poorly understood.Experimental design
To address this, we conducted a large international study to identify a cohort of 326 patients who discontinued venetoclax and have been subsequently treated. Coprimary endpoints were overall response rate (ORR) and progression-free survival for the post-venetoclax treatments stratified by treatment type [Bruton's tyrosine kinase inhibitor (BTKi), PI3K inhibitor (PI3Ki), and cellular therapies].Results
We identified patients with CLL who discontinued venetoclax in the first-line (4%) and relapsed/refractory settings (96%). Patients received a median of three therapies prior to venetoclax; 40% were BTKi naïve (n = 130), and 81% were idelalisib naïve (n = 263). ORR to BTKi was 84% (n = 44) in BTKi-naïve patients versus 54% (n = 30) in BTKi-exposed patients. We demonstrate therapy selection following venetoclax requires prior novel agent exposure consideration and discontinuation reasons.Conclusions
For BTKi-naïve patients, selection of covalently binding BTKis results in high ORR and durable remissions. For BTKi-exposed patients, covalent BTK inhibition is not effective in the setting of BTKi resistance. PI3Kis following venetoclax do not appear to result in durable remissions. We conclude that BTKi in naïve or previously responsive patients and cellular therapies following venetoclax may be the most effective strategies.See related commentary by Rogers, p. 3501.Many UC-authored scholarly publications are freely available on this site because of the UC's open access policies. Let us know how this access is important for you.
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