ATK had a consultancy with GSK, CTI Biopharma, Imago Biosciences, received honoraria from Incyte, MorphoSys, BMS, received travel support from Abbvie and MorphoSys, and participated on a Data Safety Monitoring Board or Advisory Board for Incyte. DAS had a consultancy with Abbvie, Gilead, Agios, Celyad, Foghorn, Incyte, Intellisphere, Kite, Magenta, Novartis, Affimed, Molecular Partners, PGEN Therapeutics, Takeda, and Zentalis. DAS served on the advisory board for Syros, Shattuck Labs, Jasper Therapeutics, Dark Blue Therapeutics, BMS, Syndax, Servier, Rigel Pharmaceuticals, AvenCell, Kite, Magenta, Novartis, Astellas, BlueBird Bio, Intellia, BMS, and Nkarta. DAS received research funding from Jazz Pharmaceuticals. MP had a consultancy with received honoraria from ION Pharma, Jansen Oncology, Olema Pharmaceuticals, Daiichi Sankyo, Kura Oncology, Accutar Biotech, and Nurix. AP received research funding from Monte Rosa Therapeutics, Frontier Med, Valerio, Abbvie, Immuneering, and Arvinas. LM participated on the advisory board for MorphoSys. GK received honoraria from Astellas and research funding from Prelude, Sumitomo Pharam, Schrodinger, Cyteir, and Abbvie. AV is a current equity holder in Stelexis, Clinstreet, and Bioconvergent health. AV received research funding from Prelude, BMS, Curis, and Halia. AV is a member of the board of directors or advisory committee of Stelexis, Curis and Calico. NB, MW, JR, AM, DH, SR, and WJH are current employees and equity holders of Prelude Therapeutics. OA-W is a founder and scientific advisor of Codify Therapeutics, holds equity in this company, and receives research funding from this company. OA-W has served as a consultant for Foundation Medicine Inc., Merck, Prelude Therapeutics, Amphista Therapeutics, MagnetBio, and Janssen, and is on the Scientific Advisory Board of Envisagenics Inc., Harmonic Discovery Inc., and Pfizer Boulder; OA-W has received prior research funding from H3B Biomedicine, Nurix Therapeutics, Minovia Therapeutics, and LOXO Oncology unrelated to the current manuscript. EMS received research funding from Bayer; was a consultant for Amgen, AbbVie, Seattle Genetics, and Biotheryx; served as a consultant and received research funding from Syndax; was a member of the Board of Directors or advisory committee for PTC Therapeutics and Syros; served as a consultant and was member of the Board of Directors or advisory committee for Astellas Pharmaceutical, Agios Pharmaceuticals, and Genentech; served as a consultant, received research funding, and was a member of the Board of Directors or advisory committee for Daiichi-Sankyo, Celgene Pharmaceuticals, and Novartis; and is a current equity holder in privately held Auron Therapeutics. All other authors have no conflicts of interest to declare. All conflicts of interest declared are unrelated to the content of this manuscript.

All methods were performed in accordance with the relevant guidelines and regulations. The study was approved by the review boards at the participating institutions. The names of these boards can be found in Supplementary Table 9. All patients provided written informed consent prior to enrollment in the study.