Genomic Features of Response to Combination Immunotherapy in Patients with Advanced Non-Small-Cell Lung Cancer

Cancer Cell

Volumn 33, Issue 5, 2018, Pages 843-852.e4

  Hellmann, Matthew D ^a,b   Nathanson, Tavi ^c   Rizvi, Hira ^a   Creelan, Benjamin C ^d   Sanchez Vega, Francisco ^a   Ahuja, Arun ^c   Ni, Ai ^a   Novik, Jacki B ^c   Mangarin, Levi M B ^a   Abu Akeel, Mohsen ^a   Liu, Cailian ^a   Sauter, Jennifer L ^a   Rekhtman, Natasha ^a   Chang, Eliza ^c   Callahan, Margaret K ^a,b   Chaft, Jamie E ^a,b   Voss, Martin H ^a,b   Tenet, Megan ^a   Li, Xue Mei ^e   Covello, Kelly ^e   Renninger, Andrea ^e   Vitazka, Patrik ^e   Geese, William J ^e   Borghaei, Hossein ^f   Rudin, Charles M ^a,b   Antonia, Scott J ^d   Swanton, Charles ^g,h   Hammerbacher, Jeff ^c,i   Merghoub, Taha ^a,b   McGranahan, Nicholas ^g   Snyder, Alexandra ^a   Wolchok, Jedd D ^a,b   more..

^a MEMORIAL SLOAN KETTERING CANCER CENTER   (United States)

^b WEILL CORNELL MEDICAL COLLEGE   (United States)

^c MOUNT SINAI SCHOOL OF MEDICINE   (United States)

^d H LEE MOFFITT CANCER CENTER AND RESEARCH INSTITUTE   (United States)

^e BRISTOL MYERS SQUIBB   (United States)

^f FOX CHASE CANCER CENTER   (United States)

^g UNIVERSITY COLLEGE LONDON   (United Kingdom)

^h THE FRANCIS CRICK INSTITUTE   (United Kingdom)

ⁱ MEDICAL UNIVERSITY OF SOUTH CAROLINA   (United States)

Author keywords

CTLA 4; immunotherapy; lung cancer; mutation burden; PD 1; TMB

Indexed keywords

CYTOTOXIC T LYMPHOCYTE ANTIGEN 4; IPILIMUMAB; NIVOLUMAB; PROGRAMMED DEATH 1 RECEPTOR; ANTINEOPLASTIC AGENT;

ADULT; ADVANCED CANCER; AGED; ARTICLE; CANCER IMMUNOTHERAPY; CANCER PATIENT; CLINICAL FEATURE; COHORT ANALYSIS; CONTROLLED STUDY; FEMALE; GENOMICS; HUMAN; HUMAN TISSUE; MAJOR CLINICAL STUDY; MALE; MUTATION; NON SMALL CELL LUNG CANCER; PHASE 3 CLINICAL TRIAL (TOPIC); PRIORITY JOURNAL; PROGRESSION FREE SURVIVAL; VERY ELDERLY; WHOLE EXOME SEQUENCING; GENETICS; IMMUNOTHERAPY; LUNG TUMOR; MIDDLE AGED; PROCEDURES;

ADULT; AGED; AGED, 80 AND OVER; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; CARCINOMA, NON-SMALL-CELL LUNG; FEMALE; HUMANS; IMMUNOTHERAPY; IPILIMUMAB; LUNG NEOPLASMS; MALE; MIDDLE AGED; MUTATION; NIVOLUMAB; PROGRESSION-FREE SURVIVAL; WHOLE EXOME SEQUENCING;

EID: 85045237409     PISSN: 15356108     EISSN: 18783686     Source Type: Journal    
DOI: 10.1016/j.ccell.2018.03.018     Document Type: Article

References (61)

1. Anagnostou, V., Smith, K.N., Forde, P.M., Niknafs, N., Bhattacharya, R., White, J., Zhang, T., Adleff, V., Phallen, J., Wali, N., et al. Evolution of neoantigen landscape during immune checkpoint blockade in non-small cell lung cancer. Cancer Discov. 7 (2017), 264–276.
2. Borghaei, H., Paz-Ares, L., Horn, L., Spigel, D.R., Steins, M., Ready, N.E., Chow, L.Q., Vokes, E.E., Felip, E., Holgado, E., et al. Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer. N. Engl. J. Med. 373 (2015), 1627–1639.
3. Burr, M.L., Sparbier, C.E., Chan, Y.C., Williamson, J.C., Woods, K., Beavis, P.A., Lam, E.Y.N., Henderson, M.A., Bell, C.C., Stolzenburg, S., et al. CMTM6 maintains the expression of PD-L1 and regulates anti-tumour immunity. Nature 549 (2017), 101–105.
4. Campbell, J.D., Alexandrov, A., Kim, J., Wala, J., Berger, A.H., Pedamallu, C.S., Shukla, S.A., Guo, G., Brooks, A.N., Murray, B.A., et al. Nat. Genet. 48 (2016), 607–616.
5. Carbone, D.P., Reck, M., Paz-Ares, L., Creelan, B., Horn, L., Steins, M., Felip, E., van den Heuvel, M.M., Ciuleanu, T.E., Badin, F., et al. First-line nivolumab in stage IV or recurrent non-small-cell lung cancer. N. Engl. J. Med. 376 (2017), 2415–2426.
6. Carter, S.L., Cibulskis, K., Helman, E., McKenna, A., Shen, H., Zack, T., Laird, P.W., Onofrio, R.C., Winckler, W., Weir, B.A., et al. Absolute quantification of somatic DNA alterations in human cancer. Nat. Biotechnol. 30 (2012), 413–421.
7. Chalmers, Z.R., Connelly, C.F., Fabrizio, D., Gay, L., Ali, S.M., Ennis, R., Schrock, A., Campbell, B., Shlien, A., Chmielecki, J., et al. Analysis of 100,000 human cancer genomes reveals the landscape of tumor mutational burden. Genome Med., 9, 2017, 34.
8. Cibulskis, K., Lawrence, M.S., Carter, S.L., Sivachenko, A., Jaffe, D., Sougnez, C., Gabriel, S., Meyerson, M., Lander, E.S., Getz, G., Sensitive detection of somatic point mutations in impure and heterogeneous cancer samples. Nat. Biotechnol. 31 (2013), 213–219.
9. Cibulskis, K., McKenna, A., Fennell, T., Banks, E., DePristo, M., Getz, G., ContEst: estimating cross-contamination of human samples in next-generation sequencing data. Bioinformatics 27 (2011), 2601–2602.
10. Costello, M., Pugh, T.J., Fennell, T.J., Stewart, C., Lichtenstein, L., Meldrim, J.C., Fostel, J.L., Friedrich, D.C., Perrin, D., Dionne, D., et al. Discovery and characterization of artifactual mutations in deep coverage targeted capture sequencing data due to oxidative DNA damage during sample preparation. Nucleic Acids Res., 41, 2013, e67.
11. Curran, M.A., Montalvo, W., Yagita, H., Allison, J.P., PD-1 and CTLA-4 combination blockade expands infiltrating T cells and reduces regulatory T and myeloid cells within B16 melanoma tumors. Proc. Natl. Acad. Sci. USA 107 (2010), 4275–4280.
12. DePristo, M.A., Banks, E., Poplin, R., Garimella, K.V., Maguire, J.R., Hartl, C., Philippakis, A.A., del Angel, G., Rivas, M.A., Hanna, M., et al. A framework for variation discovery and genotyping using next-generation DNA sequencing data. Nat. Genet. 43 (2011), 491–498.
13. Dong, Z.Y., Zhong, W.Z., Zhang, X.C., Su, J., Xie, Z., Liu, S.Y., Tu, H.Y., Chen, H.J., Sun, Y.L., Zhou, Q., et al. Potential predictive value of TP53 and KRAS mutation status for response to PD-1 blockade immunotherapy in lung adenocarcinoma. Clin. Cancer Res. 23 (2017), 3012–3024.
14. Eisenhauer, E.A., Therasse, P., Bogaerts, J., Schwartz, L.H., Sargent, D., Ford, R., Dancey, J., Arbuck, S., Gwyther, S., Mooney, M., et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur. J. Cancer 45 (2009), 228–247.
15. Fabrizio, D., Malboeuf, C., Lieber, D., Zhong, S., He, J., White, E., Coyne, M., Silterra, J., Brennan, T., Ma, J., et al. 102PAnalytic validation of a next generation sequencing assay to identify tumor mutational burden from blood (bTMB) to support investigation of an anti-PD-L1 agent, atezolizumab, in a first line non-small cell lung cancer trial (BFAST). Ann. Oncol., 28, 2017, mdx363.018.
16. Frampton, G.M., Fichtenholtz, A., Otto, G.A., Wang, K., Downing, S.R., He, J., Schnall-Levin, M., White, J., Sanford, E.M., An, P., et al. Development and validation of a clinical cancer genomic profiling test based on massively parallel DNA sequencing. Nat. Biotechnol. 31 (2013), 1023–1031.
17. Gandara, D.R., Kowanetz, M., Mok, T.S.K., Rittmeyer, A., Fehrenbacher, L., Fabrizio, D., Otto, G., Malboeuf, C., Lieber, D., Paul, S.M., et al. 1295OBlood-based biomarkers for cancer immunotherapy: tumor mutational burden in blood (bTMB) is associated with improved atezolizumab (atezo) efficacy in 2L+ NSCLC (POPLAR and OAK). Ann. Oncol., 28, 2017, mdx380.
18. Gao, J., Shi, L.Z., Zhao, H., Chen, J., Xiong, L., He, Q., Chen, T., Roszik, J., Bernatchez, C., Woodman, S.E., et al. Loss of IFN-gamma pathway genes in tumor cells as a mechanism of resistance to anti-CTLA-4 therapy. Cell 167 (2016), 397–404.e9.
19. George, S., Miao, D., Demetri, G.D., Adeegbe, D., Rodig, S.J., Shukla, S., Lipschitz, M., Amin-Mansour, A., Raut, C.P., Carter, S.L., et al. Loss of PTEN is associated with resistance to anti-PD-1 checkpoint blockade therapy in metastatic uterine leiomyosarcoma. Immunity 46 (2017), 197–204.
20. Glanville, J., Huang, H., Nau, A., Hatton, O., Wagar, L.E., Rubelt, F., Ji, X., Han, A., Krams, S.M., Pettus, C., et al. Identifying specificity groups in the T cell receptor repertoire. Nature 547 (2017), 94–98.
21. Goodman, A.M., Kato, S., Bazhenova, L., Patel, S.P., Frampton, G.M., Miller, V., Stephens, P.J., Daniels, G.A., Kurzrock, R., Tumor mutational burden as an independent predictor of response to immunotherapy in diverse cancers. Mol. Cancer Ther. 16 (2017), 2598–2608.
22. Gubin, M.M., Zhang, X., Schuster, H., Caron, E., Ward, J.P., Noguchi, T., Ivanova, Y., Hundal, J., Arthur, C.D., Krebber, W.J., et al. Checkpoint blockade cancer immunotherapy targets tumour-specific mutant antigens. Nature 515 (2014), 577–581.
23. Hadrup, S.R., Bakker, A.H., Shu, C.J., Andersen, R.S., van Veluw, J., Hombrink, P., Castermans, E., Thor Straten, P., Blank, C., Haanen, J.B., et al. Parallel detection of antigen-specific T-cell responses by multidimensional encoding of MHC multimers. Nat. Methods 6 (2009), 520–526.
24. Hammers, H.J., Plimack, E.R., Infante, J.R., Rini, B.I., McDermott, D.F., Lewis, L.D., Voss, M.H., Sharma, P., Pal, S.K., Razak, A.R.A., et al. Safety and efficacy of nivolumab in combination with ipilimumab in metastatic renal cell carcinoma: the CheckMate 016 study. J. Clin. Oncol. 35 (2017), 3851–3858.
25. Hellmann, M.D., Callahan, M.K., Awad, M.M., Calvo, E., Ascierto, P.A., Atmaca, A., Rizvi, N.A., Hirsch, F.R., Selvaggi, G., Szustakowski, J.D., et al. Tumor mutation burden and efficacy of nivolumab monotherapy and in combination with ipilimumab in small cell lung cancer. Cancer Cell, 2018, 10.1016/j.ccell.2018.04.001.
26. Hellmann, M.D., Rizvi, N.A., Goldman, J.W., Gettinger, S.N., Borghaei, H., Brahmer, J.R., Ready, N.E., Gerber, D.E., Chow, L.Q., Juergens, R.A., et al. Nivolumab plus ipilimumab as first-line treatment for advanced non-small-cell lung cancer (CheckMate 012): results of an open-label, phase 1, multicohort study. Lancet Oncol. 18 (2017), 31–41.
27. Karosiene, E., Lundegaard, C., Lund, O., Nielsen, M., NetMHCcons: a consensus method for the major histocompatibility complex class I predictions. Immunogenetics 64 (2012), 177–186.
28. Landau, D.A., Carter, S.L., Stojanov, P., McKenna, A., Stevenson, K., Lawrence, M.S., Sougnez, C., Stewart, C., Sivachenko, A., Wang, L., et al. Evolution and impact of subclonal mutations in chronic lymphocytic leukemia. Cell 152 (2013), 714–726.
29. Lawrence, M.S., Stojanov, P., Polak, P., Kryukov, G.V., Cibulskis, K., Sivachenko, A., Carter, S.L., Stewart, C., Mermel, C.H., Roberts, S.A., et al. Mutational heterogeneity in cancer and the search for new cancer-associated genes. Nature 499 (2013), 214–218.
30. Le, D.T., Durham, J.N., Smith, K.N., Wang, H., Bartlett, B.R., Aulakh, L.K., Lu, S., Kemberling, H., Wilt, C., Luber, B.S., et al. Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. Science 357 (2017), 409–413.
31. Levine, A.J., Oren, M., The first 30 years of p53: growing ever more complex. Nat. Rev. Cancer 9 (2009), 749–758.
32. Li, H., Durbin, R., Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics 25 (2009), 1754–1760.
33. Luksza, M., Riaz, N., Makarov, V., Balachandran, V.P., Hellmann, M.D., Solovyov, A., Rizvi, N.A., Merghoub, T., Levine, A.J., Chan, T.A., et al. A neoantigen fitness model predicts tumour response to checkpoint blockade immunotherapy. Nature 551 (2017), 517–520.
34. Manguso, R.T., Pope, H.W., Zimmer, M.D., Brown, F.D., Yates, K.B., Miller, B.C., Collins, N.B., Bi, K., LaFleur, M.W., Juneja, V.R., et al. In vivo CRISPR screening identifies Ptpn2 as a cancer immunotherapy target. Nature 547 (2017), 413–418.
35. McGranahan, N., Furness, A.J., Rosenthal, R., Ramskov, S., Lyngaa, R., Saini, S.K., Jamal-Hanjani, M., Wilson, G.A., Birkbak, N.J., Hiley, C.T., et al. Clonal neoantigens elicit T cell immunoreactivity and sensitivity to immune checkpoint blockade. Science 351 (2016), 1463–1469.
36. Mezzadra, R., Sun, C., Jae, L.T., Gomez-Eerland, R., de Vries, E., Wu, W., Logtenberg, M.E.W., Slagter, M., Rozeman, E.A., Hofland, I., et al. Identification of CMTM6 and CMTM4 as PD-L1 protein regulators. Nature 549 (2017), 106–110.
37. Nathanson, T., Ahuja, A., Rubinsteyn, A., Aksoy, B.A., Hellmann, M.D., Miao, D., Van Allen, E., Merghoub, T., Wolchok, J.D., Snyder, A., Hammerbacher, J., Somatic mutations and neoepitope homology in melanomas treated with CTLA-4 blockade. Cancer Immunol. Res. 5 (2017), 84–91.
38. Ott, P.A., Hu, Z., Keskin, D.B., Shukla, S.A., Sun, J., Bozym, D.J., Zhang, W., Luoma, A., Giobbie-Hurder, A., Peter, L., et al. An immunogenic personal neoantigen vaccine for patients with melanoma. Nature 547 (2017), 217–221.
39. Patel, S.J., Sanjana, N.E., Kishton, R.J., Eidizadeh, A., Vodnala, S.K., Cam, M., Gartner, J.J., Jia, L., Steinberg, S.M., Yamamoto, T.N., et al. Identification of essential genes for cancer immunotherapy. Nature 548 (2017), 537–542.
40. Pfeifer, G.P., Denissenko, M.F., Olivier, M., Tretyakova, N., Hecht, S.S., Hainaut, P., Tobacco smoke carcinogens, DNA damage and p53 mutations in smoking-associated cancers. Oncogene 21 (2002), 7435–7451.
41. Reck, M., Rodriguez-Abreu, D., Robinson, A.G., Hui, R., Csoszi, T., Fulop, A., Gottfried, M., Peled, N., Tafreshi, A., Cuffe, S., et al. Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer. N. Engl. J. Med. 375 (2016), 1823–1833.
42. Rizvi, N.A., Hellmann, M.D., Snyder, A., Kvistborg, P., Makarov, V., Havel, J.J., Lee, W., Yuan, J., Wong, P., Ho, T.S., et al. Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science 348 (2015), 124–128.
43. Rizvi, H., Sanchez-Vega, F., La, K., Chatila, W., Jonsson, P., Halpenny, D., Plodkowski, A., Long, N., Sauter, J.L., Rekhtman, N., et al. Molecular determinants of response to anti-programmed cell death (PD)-1 and anti-programmed death-ligand (PD-L)-Ligand 1 blockade in patients with non-small-cell lung cancer profiled with targeted next-generation sequencing. J. Clin. Oncol. 36 (2018), 633–641.
44. Rooney, M.S., Shukla, S.A., Wu, C.J., Getz, G., Hacohen, N., Molecular and genetic properties of tumors associated with local immune cytolytic activity. Cell 160 (2015), 48–61.
45. Rosenberg, J.E., Hoffman-Censits, J., Powles, T., van der Heijden, M.S., Balar, A.V., Necchi, A., Dawson, N., O'Donnell, P.H., Balmanoukian, A., Loriot, Y., et al. Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: a single-arm, multicentre, phase 2 trial. Lancet 387 (2016), 1909–1920.
46. Sahin, U., Derhovanessian, E., Miller, M., Kloke, B.P., Simon, P., Lower, M., Bukur, V., Tadmor, A.D., Luxemburger, U., Schrors, B., et al. Personalized RNA mutanome vaccines mobilize poly-specific therapeutic immunity against cancer. Nature 547 (2017), 222–226.
47. Schumacher, T.N., Schreiber, R.D., Neoantigens in cancer immunotherapy. Science 348 (2015), 69–74.
48. Skoulidis, F., Byers, L.A., Diao, L., Papadimitrakopoulou, V.A., Tong, P., Izzo, J., Behrens, C., Kadara, H., Parra, E.R., Canales, J.R., et al. Co-occurring genomic alterations define major subsets of KRAS-mutant lung adenocarcinoma with distinct biology, immune profiles, and therapeutic vulnerabilities. Cancer Discov. 5 (2015), 860–877.
49. Snyder, A., Makarov, V., Merghoub, T., Yuan, J., Zaretsky, J.M., Desrichard, A., Walsh, L.A., Postow, M.A., Wong, P., Ho, T.S., et al. Genetic basis for clinical response to CTLA-4 blockade in melanoma. N.Engl. J. Med. 371 (2014), 2189–2199.
50. Snyder, A., Nathanson, T., Funt, S.A., Ahuja, A., Buros Novik, J., Hellmann, M.D., Chang, E., Aksoy, B.A., Al-Ahmadie, H., Yusko, E., et al. Contribution of systemic and somatic factors to clinical response and resistance to PD-L1 blockade in urothelial cancer: an exploratory multi-omic analysis. PLoS Med., 14, 2017, e1002309.
51. Szolek, A., Schubert, B., Mohr, C., Sturm, M., Feldhahn, M., Kohlbacher, O., OptiType: precision HLA typing from next-generation sequencing data. Bioinformatics 30 (2014), 3310–3316.
52. Taube, J.M., Klein, A., Brahmer, J.R., Xu, H., Pan, X., Kim, J.H., Chen, L., Pardoll, D.M., Topalian, S.L., Anders, R.A., Association of PD-1, PD-1 ligands, and other features of the tumor immune microenvironment with response to anti-PD-1 therapy. Clin. Cancer Res. 20 (2014), 5064–5074.
53. Taylor-Weiner, A., Zack, T., O'Donnell, E., Guerriero, J.L., Bernard, B., Reddy, A., Han, G.C., AlDubayan, S., Amin-Mansour, A., Schumacher, S.E., et al. Genomic evolution and chemoresistance in germ-cell tumours. Nature 540 (2016), 114–118.
54. Tran, E., Ahmadzadeh, M., Lu, Y.C., Gros, A., Turcotte, S., Robbins, P.F., Gartner, J.J., Zheng, Z., Li, Y.F., Ray, S., et al. Immunogenicity of somatic mutations in human gastrointestinal cancers. Science 350 (2015), 1387–1390.
55. Van Allen, E.M., Miao, D., Schilling, B., Shukla, S.A., Blank, C., Zimmer, L., Sucker, A., Hillen, U., Foppen, M.H., Goldinger, S.M., et al. Genomic correlates of response to CTLA-4 blockade in metastatic melanoma. Science 350 (2015), 207–211.
56. Van Allen, E.M., Wagle, N., Stojanov, P., Perrin, D.L., Cibulskis, K., Marlow, S., Jane-Valbuena, J., Friedrich, D.C., Kryukov, G., Carter, S.L., et al. Whole-exome sequencing and clinical interpretation of formalin-fixed, paraffin-embedded tumor samples to guide precision cancer medicine. Nat. Med. 20 (2014), 682–688.
57. van Rooij, N., van Buuren, M.M., Philips, D., Velds, A., Toebes, M., Heemskerk, B., van Dijk, L.J., Behjati, S., et al. Tumor exome analysis reveals neoantigen-specific T-cell reactivity in an ipilimumab-responsive melanoma. J. Clin. Oncol. 31 (2013), e439–e442.
58. Wei, S.C., Levine, J.H., Cogdill, A.P., Zhao, Y., Anang, N.A.S., Andrews, M.C., Sharma, P., Wang, J., Wargo, J.A., Pe'er, D., Allison, J.P., Distinct cellular mechanisms underlie anti-CTLA-4 and anti-PD-1 checkpoint blockade. Cell 170 (2017), 1120–1133.e17.
59. Wolchok, J.D., Chiarion-Sileni, V., Gonzalez, R., Rutkowski, P., Grob, J.J., Cowey, C.L., Lao, C.D., Wagstaff, J., Schadendorf, D., Ferrucci, P.F., et al. Overall survival with combined nivolumab and ipilimumab in advanced melanoma. N. Engl. J. Med. 377 (2017), 1345–1356.
60. Zaretsky, J.M., Garcia-Diaz, A., Shin, D.S., Escuin-Ordinas, H., Hugo, W., Hu-Lieskovan, S., Torrejon, D.Y., Abril-Rodriguez, G., Sandoval, S., Barthly, L., et al. Mutations associated with acquired resistance to PD-1 blockade in melanoma. N. Engl. J. Med. 375 (2016), 819–829.
61. Zehir, A., Benayed, R., Shah, R.H., Syed, A., Middha, S., Kim, H.R., Srinivasan, P., Gao, J., Chakravarty, D., Devlin, S.M., et al. Mutational landscape of metastatic cancer revealed from prospective clinical sequencing of 10,000 patients. Nat. Med. 23 (2017), 703–713.