High total metabolic tumor volume at baseline predicts survival independent of response to therapy
Laetitia Vercellino, Anne-Segolene Cottereau, Olivier Casasnovas, Hervé Tilly, Pierre Feugier, Loic Chartier, Christophe Fruchart, Louise Roulin, Lucie Oberic, Gian Matteo Pica, Vincent Ribrag, Julie Abraham, Marc Simon, Hugo Gonzalez, Reda Bouabdallah, Olivier Fitoussi, Catherine Sebban, Armando López-Guillermo, Laurence Sanhes, Franck Morschhauser, Judith Trotman, Bernadette Corront, Bachra Choufi, Sylvia Snauwaert, Pascal Godmer, Josette Briere, Gilles Salles, Philippe Gaulard, Michel Meignan, Catherine Thieblemont, Laetitia Vercellino, Anne-Segolene Cottereau, Olivier Casasnovas, Hervé Tilly, Pierre Feugier, Loic Chartier, Christophe Fruchart, Louise Roulin, Lucie Oberic, Gian Matteo Pica, Vincent Ribrag, Julie Abraham, Marc Simon, Hugo Gonzalez, Reda Bouabdallah, Olivier Fitoussi, Catherine Sebban, Armando López-Guillermo, Laurence Sanhes, Franck Morschhauser, Judith Trotman, Bernadette Corront, Bachra Choufi, Sylvia Snauwaert, Pascal Godmer, Josette Briere, Gilles Salles, Philippe Gaulard, Michel Meignan, Catherine Thieblemont
Abstract
Early identification of ultra-risk diffuse large B-cell lymphoma (DLBCL) patients is needed to aid stratification to innovative treatment. Previous studies suggested high baseline total metabolic tumor volume (TMTV) negatively impacts survival of DLBCL patients. We analyzed the prognostic impact of TMTV and prognostic indices in DLBCL patients, aged 60 to 80 years, from the phase 3 REMARC study that randomized responding patients to R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) into maintenance lenalidomide or placebo. TMTV was computed on baseline positron emission tomography/computed tomography using the 41% maximum standardized uptake value method; the optimal TMTV cutoff for progression-free (PFS) and overall survival (OS) was determined and confirmed by a training validation method. There were 301 out of 650 evaluable patients, including 192 patients classified as germinal center B-cell-like (GCB)/non-GCB and MYC/BCL2 expressor. Median baseline TMTV was 238 cm3; optimal TMTV cutoff was 220 cm3. Patients with high vs low TMTV showed worse/higher Eastern Cooperative Oncology Group performance status (ECOG PS) ≥2, stage III or IV disease, >1 extranodal site, elevated lactate dehydrogenase, International Prognostic Index (IPI) 3-5, and age-adjusted IPI 2-3. High vs low TMTV significantly impacted PFS and OS, independent of maintenance treatment. Although the GCB/non-GCB profile and MYC expression did not correlate with TMTV/survival, BCL2 >70% impacted PFS and could be stratified by TMTV. Multivariate analysis identified baseline TMTV and ECOG PS as independently associated with PFS and OS. Even in responding patients, after R-CHOP, high baseline TMTV was a strong prognosticator of inferior PFS and OS. Moreover, TMTV combined with ECOG PS may identify an ultra-risk DLBCL population. This trial was registered at www.clinicaltrials.gov as #NCT01122472.
Conflict of interest statement
Conflict-of-interest disclosure: O.C. received research funding from Roche, Takeda, and Gilead and is on the advisory board of or received honoraria from Celgene, Roche, Takeda, Gilead, BMS, Merck, Abbvie, and Janssen outside the submitted work. H.T. received research funding and personal fees from Celgene; personal fees and nonfinancial support from Roche; and personal fees from Takeda, Janssen, Gilead, and Karyopharm outside the submitted work. P.F. received honoraria and travel accommodations from and had a consulting/advisory role with Roche/Genentech, Janssen, Gilead, and Abbvie. L.O. and R.B. received funding from Roche. V.R. received honoraria from Infinity Pharmaceuticals, BMS, Eisai, PharmaMar, and Gilead Sciences; had a consulting/advisory role with Infinity Pharmaceuticals, BMS, PharmaMar, Gilead Sciences, NanoString Technologies, Incyte, BMS, MSD, Roche/Genentech, Epizyme, AstraZeneca, and immune design; received research funding from arGEN-X BVBA; has patents, royalties, and other intellectual property regarding BAY1000394 studies on mantle cell lymphoma; provided expert testimony for Servier; received travel/accommodation expense funding from Roche, BMS, and AstraZeneca; and received research grants from AstraZeneca, BMS, Boehringer Ingelheim, Janssen Cilag, Merck, Novartis, Pfizer, Roche, and Sanofi. F.M. had an advisory role with and received honoraria from Celgene, Roche, Gilead Sciences, Servier, Epizyme, BMS, Bayer, and Novartis and received honoraria from Janssen. P. Godmer was invited to a congress/conference by Celgene. G.S. received financial compensation for participating in advisory boards or consulting from Abbvie, Autolus, Celgene, Gilead, Epizyme, Janssen, Karyopharm, Kite, Merck, Morphosys, Novartis, Roche, Servier, and Takeda and participated in educational events for Abbvie, Amgen, Celgene, Gilead, Janssen, Kite, Morphosys, Novartis, Roche, Servier, Takeda. P. Gaulard received research funding from Takeda and Innate Pharma and is on the advisory board and received honoraria from Takeda. C.T. received honoraria from Roche, Amgen, Janssen, Celgene, Gilead Science/Kyte; had a consulting/advisory role with Roche, Gilead Sciences, Janssen, Celgene, and Novartis; and received research and travel/accommodation expense funding from Roche and Novartis. The remaining authors declare no competing financial interests.
© 2020 by The American Society of Hematology.
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Source: PubMed