Rapid, real time pathology review for ECOG/ACRIN 1412: a novel and successful paradigm for future lymphoma clinical trials in the precision medicine era

Rebecca L King, Grzegorz S Nowakowski, Thomas E Witzig, David W Scott, Richard F Little, Fangxin Hong, Randy D Gascoyne, Brad S Kahl, William R Macon, Rebecca L King, Grzegorz S Nowakowski, Thomas E Witzig, David W Scott, Richard F Little, Fangxin Hong, Randy D Gascoyne, Brad S Kahl, William R Macon

Abstract

ECOG/ACRIN 1412 (E1412) is a randomized, phase II open-label study of lenalidomide/RCHOP vs. RCHOP alone in adults with newly diagnosed de novo diffuse large B-cell lymphoma (DLBCL) and requires NanoString gene expression profiling (GEP) for cell-of-origin testing. Because of high ineligibility rate on retrospective expert central pathology review (ECPR), real-time (RT) ECPR was instituted to confirm diagnosis and ensure adequate tissue for GEP prior to study enrollment. Goal was notification of eligibility within 2 working days (WD). Initially, 208 patients were enrolled, 74 (35.6%) of whom were deemed ineligible by retrospective ECPR. After initiation of RT-ECPR, 219 patients were registered. Of these, 73 (33.3%) were ineligible and were declined enrollment; 47 (21.5% of total) had an ineligible diagnosis on RT-ECPR, and 26 (11.9% of total) had inadequate tissue. Because the 73 ineligible patients were never enrolled, no study slots were "lost" during this phase. Notification of eligibility occurred in an average of 1 WD (Range 0-4) with 97.3% within 2 WD. This novel RT-ECPR serves as a model for future lymphoma trials. Real-time ECPR can help to reduce costs and ensure that study slots accurately reflect the targeted population. In the precision-medicine era, rapid collection of relevant pathology/biomarker data is essential to trial success.

Trial registration: ClinicalTrials.gov NCT01856192.

Conflict of interest statement

G.S.N., MD: Celgene, Roche, Bayer, MorphoSys and Nanostring-Consulting (no personal compensation, money to Mayo): Celgene, Bayer, MorphoSys, AbbVie, Pharmacyclics, and Roche. D.W.S., MBChB, PhD: Consultant for Celgene. Inventor on a patent: “Methods for selecting and treating lymphoma types.” (Institution). B.S.K., MD: Performed consulting for Genentech and Celgene and receives research funding from Genentech and Celgene. The remaining authors declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1
Schematic of traditional vs. real-time expert central pathology review

References

    1. Swerdlow SH, et al. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. 4th ed. Lyon, France: IARC; 2008.
    1. Swerdlow SH, et al. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. 4th ed. Lyon: IARC; 2017.
    1. Zelenetz AD, et al. Diffuse large B-cell lymphoma version 1.2016. J. Natl. Compr. Canc. Netw. 2016;14:196–231. doi: 10.6004/jnccn.2016.0023.
    1. Rosenwald A, et al. The use of molecular profiling to predict survival after chemotherapy for diffuse large-B-cell lymphoma. N. Engl. J. Med. 2002;346:1937–1947. doi: 10.1056/NEJMoa012914.
    1. Sarkozy C, Traverse-Glehen A, Coiffier B. Double-hit and double-protein-expression lymphomas: aggressive and refractory lymphomas. Lancet Oncol. 2015;16:e555–e567. doi: 10.1016/S1470-2045(15)00005-4.
    1. Scott DW, et al. Determining cell-of-origin subtypes of diffuse large B-cell lymphoma using gene expression in formalin-fixed paraffin-embedded tissue. Blood. 2014;123:1214–1217. doi: 10.1182/blood-2013-11-536433.
    1. Staiger AM, et al. Clinical impact of the cell-of-origin classification and the MYC/ BCL2 dual expresser status in diffuse large B-cell lymphoma treated within prospective clinical trials of the german high-grade non-Hodgkin’s Lymphoma Study Group. J. Clin. Oncol. 2017;35:2515–2526. doi: 10.1200/JCO.2016.70.3660.
    1. Nowakowski GS, Vitolo U. Recent advances in clinical studies and the evolving role of subtyping for patients with diffuse large B-cell lymphoma. Future Oncol. 2017;13:859–862. doi: 10.2217/fon-2016-0567.
    1. Nowakowski, G. S. & Czuczman, M. S. ABC, GCB, and double-hit diffuse large B-cell lymphoma: does subtype make a difference in therapy selection? Am. Soc. Clin. Oncol. Educ. Book. e449–e457 (2015). .
    1. Nowakowski GS, et al. Beyond RCHOP: a blueprint for diffuse large B cell lymphoma research. J. Natl. Cancer Inst. 2016;108:djw257. doi: 10.1093/jnci/djw257.
    1. Nowakowski GS, et al. ROBUST: lenalidomide-R-CHOP versus placebo-R-CHOP in previously untreated ABC-type diffuse large B-cell lymphoma. Future Oncol. 2016;12:1553–1563. doi: 10.2217/fon-2016-0130.
    1. Moore EM, Aggarwal N, Surti U, Swerdlow SH. Further exploration of the complexities of large B-Cell lymphomas with MYC abnormalities and the importance of a blastoid morphology. Am. J. Surg. Pathol. 2017;41:1155–1166. doi: 10.1097/PAS.0000000000000818.
    1. Manso BA, et al. Whole-exome analysis reveals novel somatic genomic alterations associated with cell of origin in diffuse large B-cell lymphoma. Blood Cancer J. 2017;7:e553. doi: 10.1038/bcj.2017.33.
    1. Maurer MJ, et al. Personalized risk prediction for event-free survival at 24 months in patients with diffuse large B-cell lymphoma. Am. J. Hematol. 2016;91:179–184. doi: 10.1002/ajh.24223.
    1. Haioun C, et al. Rituximab versus observation after high-dose consolidative first-line chemotherapy with autologous stem-cell transplantation in patients with poor-risk diffuse large B-cell lymphoma. Ann. Oncol. 2009;20:1985–1992. doi: 10.1093/annonc/mdp237.
    1. Teras LR, et al. 2016 US lymphoid malignancy statistics by World Health Organization subtypes. Ca. Cancer J. Clin. 2016;66:443–459. doi: 10.3322/caac.21357.
    1. Howlader N, et al. Cancer-specific mortality, cure fraction, and noncancer causes of death among diffuse large B-cell lymphoma patients in the immunochemotherapy era. Cancer. 2017;123:3326–3334. doi: 10.1002/cncr.30739.
    1. National Cancer Institute—Bethesda. Cancer Stat Facts: Non-Hodgkin Lymphoma (2017).
    1. Bowen JM, et al. Lymphoma diagnosis at an academic centre: rate of revision and impact on patient care. Br. J. Haematol. 2014;166:202–208. doi: 10.1111/bjh.12880.
    1. Cook IS, McCormick D, Poller DN. Referrals for second opinion in surgical pathology: implications for management of cancer patients in the UK. Eur. J. Surg. Oncol. (EJSO). 2001;27:589–594. doi: 10.1053/ejso.2001.1150.
    1. LaCasce AS, et al. Comparison of referring and final pathology for patients with non-Hodgkin’s lymphoma in the National Comprehensive Cancer Network. J. Clin. Oncol. 2008;26:5107–5112. doi: 10.1200/JCO.2008.16.4061.
    1. Lester JF, et al. The clinical impact of expert pathological review on lymphoma management: a regional experience. Br. J. Haematol. 2003;123:463–468. doi: 10.1046/j.1365-2141.2003.04629.x.
    1. Matasar MJ, et al. Expert second-opinion pathology review of lymphoma in the era of the World Health Organization classification. Ann. Oncol. 2012;23:159–166. doi: 10.1093/annonc/mdr029.
    1. Prescott RJ, Wells S, Bisset DL, Banerjee SS, Harris M. Audit of tumour histopathology reviewed by a regional oncology centre. J. Clin. Pathol. 1995;48:245–249. doi: 10.1136/jcp.48.3.245.
    1. Proctor IE, McNamara C, Rodriguez-Justo M, Isaacson PG, Ramsay A. Importance of expert central review in the diagnosis of lymphoid malignancies in a regional cancer network. J. Clin. Oncol. 2011;29:1431–1435. doi: 10.1200/JCO.2010.31.2223.
    1. Swapp RE, Aubry MC, Salomão DR, Cheville JC. Outside case review of surgical pathology for referred patients: the impact on patient care. Arch. Pathol. Lab. Med. 2013;137:233–240. doi: 10.5858/arpa.2012-0088-OA.
    1. Laurent C, et al. Impact of expert pathologic review of lymphoma diagnosis: study of patients from the French lymphopath network. J. Clin. Oncol. 2017;35:2008–2017. doi: 10.1200/JCO.2016.71.2083.
    1. Puvvada SD, et al. A phase II study of belinostat (PXD101) in relapsed and refractory aggressive B-cell lymphomas: SWOG S0520. Leuk. Lymphoma. 2016;57:2359–2369. doi: 10.3109/10428194.2015.1135431.
    1. Stiff PJ, et al. Autologous transplantation as consolidation for aggressive non-Hodgkin’s lymphoma. N. Engl. J. Med. 2013;369:1681–1690. doi: 10.1056/NEJMoa1301077.
    1. Stopeck AT, et al. A phase 2 trial of standard-dose cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) and rituximab plus bevacizumab for patients with newly diagnosed diffuse large B-cell non-Hodgkin lymphoma: SWOG 0515. Blood. 2012;120:1210–1217. doi: 10.1182/blood-2012-04-423079.
    1. Stopeck AT, et al. A phase II trial of single agent bevacizumab in patients with relapsed, aggressive non-Hodgkin lymphoma: Southwest oncology group study S0108. Leuk. Lymphoma. 2009;50:728–735. doi: 10.1080/10428190902856808.
    1. Persky DO, et al. Phase II study of rituximab plus three cycles of CHOP and involved-field radiotherapy for patients with limited-stage aggressive B-cell lymphoma: Southwest Oncology Group study 0014. J. Clin. Oncol. 2008;26:2258–2263. doi: 10.1200/JCO.2007.13.6929.
    1. Swinnen LJ, et al. Response-adapted therapy for aggressive non-Hodgkin’s lymphomas based on early [18F] FDG-PET scanning: ECOG-ACRIN Cancer Research Group study (E3404) Br. J. Haematol. 2015;170:56–65. doi: 10.1111/bjh.13389.
    1. Leonard JP, Martin P, Roboz GJ. Practical implications of the 2016 revision of the World Health Organization classification of lymphoid and myeloid neoplasms and acute leukemia. J. Clin. Oncol. 2017;35:2708–2715. doi: 10.1200/JCO.2017.72.6745.
    1. Zinzani PL, et al. Ultrasound-guided core-needle biopsy is effective in the initial diagnosis of lymphoma patients. Haematologica. 1998;83:989–992.
    1. de Margerie-Mellon C, et al. Diagnostic yield and safety of computed tomography-guided mediastinal core needle biopsies. J. Thorac. Imaging. 2015;30:319–327. doi: 10.1097/RTI.0000000000000160.
    1. Jin M, Wakely PE., Jr. Endoscopic/endobronchial ultrasound-guided fine needle aspiration and ancillary techniques, particularly flow cytometry, in diagnosing deep-seated lymphomas. Acta Cytol. 2016;60:326–335. doi: 10.1159/000447253.

Source: PubMed

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