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4298 R-DA-EPOCH Treatment Is Highly Effective Therapy for Primary Mediastinal Large B-Cell Lymphoma: A Real-World Multi-Centre Retrospective Evaluation

Program: Oral and Poster Abstracts
Session: 627. Aggressive Lymphomas: Clinical and Epidemiological: Poster III
Hematology Disease Topics & Pathways:
Research, Lymphomas, Clinical Research, B Cell lymphoma, Combination therapy, Diseases, real-world evidence, Therapies, Lymphoid Malignancies
Monday, December 12, 2022, 6:00 PM-8:00 PM

Anna Santarsieri1*, Rory Bennett2*, David Hopkins3*, Katharine L. Lewis, MBBS, MRCP, FRCPath4, Cecilia N Gyansah5*, Lisa Cooke6*, Sateesh K. Nagumantry7*, Nimish K. Shah5*, Chan Y. Cheah4, Pamela McKay, MD3*, Michael Dickinson, MD8, John F. Seymour, MBBS, PhD, FRACP2 and George A Follows1*

1Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom
2Peter MacCallum Cancer Centre, Melbourne, VIC, Australia
3Beatson West of Scotland Cancer Centre, Glasgow, United Kingdom
4Sir Charles Gairdner Hospital, University of Western Australia, Perth, Western Australia, Australia
5Norfolk and Norwich University Hospitals NHS Foundation Trust, Norwich, United Kingdom
6The Queen Elizabeth Hospital King's Lynn NHS Foundation Trust, King's Lynn, United Kingdom
7Peterborough City Hospital, Peterborough, United Kingdom
8Peter MacCallum Cancer Centre, Royal Melbourne Hospital and The University of Melbourne, Melbourne, Australia

Primary mediastinal large B-cell lymphoma (PMBL) is an aggressive non-Hodgkin lymphoma which typically presents in young adults with a bulky mediastinal mass. Standard immunochemotherapy with R-CHOP21 alone is associated with a significant relapse risk if consolidative radiotherapy (RT) is omitted (Chan et al. Cancer Medicine. 2019; 8: 4626-4632). Dose-intensified regimens such as R-CHOP14, R-VACOP-B and R-DA-EPOCH have been reported to deliver better outcomes than R-CHOP21 with reduced requirement for RT and associated long-term risks, although direct randomised comparisons of regimens are lacking. Following publication of the prospective NCI trial which showed R-DA-EPOCH achieves excellent event-free (EFS) and overall survival (OS) without the need for RT (Dunleavy et al. NEJM. 2013; 368: 1408-1416), this regimen was adopted as a standard of care at multiple centres internationally. To date, few large real-world studies of R-DA-EPOCH with long-term follow-up have been published. Here we present a retrospective study of 122 adults from 9 centres in England, Scotland and Australia who were treated with first-line R-DA-EPOCH for PMBL 2010 - 2022 with a median follow-up of 3.2 (range: 0.3 – 11.6) years.

Patients (pts) had a median age of 34.1 years at diagnosis, with female preponderance (60%). Disease bulk (≥10cm) was present in 62%, 83% had raised LDH and 64% had stage 1-2 disease. Age-adjusted International Prognostic Index was 0,1,2 and 3 in 15%, 44%, 34% and 7% respectively.

The majority of pts received 6 cycles of R-DA-EPOCH (87%); only 4% completed <5 cycles. Of note, 13% of pts received R-CHOP as their first cycle of chemotherapy for stabilisation before commencing R-DA-EPOCH. The use of interim PET-CT (iPET) varied between institutions, with 72% (88/122) having an iPET after 2, 3 or 4 cycles (n=54, 30, 4, respectively). Likewise, end of treatment PET (ePET) was performed in 85% (104/122), being omitted in certain pts who had achieved a metabolic remission on iPET. Of the iPET pts, 41% achieved complete metabolic response (CMR) (Deauville Score [DS] ≤3), with no statistical difference in proportions between iPET2 and iPET3. 69% of iPET negative patients had an ePET and all remained DS ≤3 on ePET, while 59% (29/49) of iPET positive patients who had an ePET became DS≤3. Of all the ePET pts, 72% achieved DS ≤3. Consolidative RT was delivered more frequently in this real-world cohort than in the prospective trial, with 31% of pts receiving RT (16/75 (21%) of ePET DS≤3 pts and 16/29 (55%) of ePET DS4+ pts).

With a median follow-up of 3.2 years, 3-year PFS was 92.8% (95% CI: 88.1-97.7%), and 3-year OS was 97.2% (94.2-100%). There have been 8 progression events, with 6 cases of primary refractory disease at or before the ePET scan, and two relapses at 6 and 7 months after completing chemotherapy. Both of these pts had achieved ePET DS≤3 and had no RT. Of the 98 pts followed up beyond 1 year, no relapses have been observed. Of pts who had an initial cycle of R-CHOP, one has progressed with refractory disease after 5 x R-DA-EPOCH. 121/122 pts had at least 1 PET scan - 74% (90/121) achieved CMR on either iPET / ePET or both and the negative predictive values for relapse after achieving CMR on iPET and ePET was 97.2% and 97.3% respectively. Of 31 pts who failed to achieve a PET DS≤3 on either iPET (23 pts) or ePET (28 pts), 81% (25/31) have not relapsed. Of the 23 ePET DS4 patients, none have relapsed, but 14 / 23 had RT. Of the 8 ePET DS5 patients, 3 remain disease free with 2/3 receiving RT. Of the 10 ePET DS4-5 pts who did not receive RT, 70% (7/10) achieved CMR at mean 4.4 months after final chemotherapy, whilst 30% (3/10) pts remain PET positive but have not required further treatment.

There have been 4 deaths in total (3 refractory disease and 1 death due to complications of allogeneic transplant). Two second malignancies (Hodgkin lymphoma at 4 years, serous ovarian malignancy at 3.5 years) have been reported and pregnancy data will be presented.

In conclusion, with this large multi-centre real-world dataset with long-term follow-up, we demonstrate that R-DA-EPOCH is a highly effective regimen to treat PMBL and that potentially, ePET has little additional utility in pts with CMR on iPET. The use of RT appears more widespread in real-world practice as the majority of pts who were ePET DS4+ were treated with RT. Pts who achieved a metabolic remission on either interim or end of treatment PET/CT had a very low relapse risk and no relapses beyond 1 year were reported.

Disclosures: Santarsieri: Takeda: Other: Conference funding 2021; Janssen: Honoraria. Lewis: AstraZeneca: Consultancy, Honoraria; IQVIA: Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Patents & Royalties; Loxo-Lilly: Membership on an entity's Board of Directors or advisory committees, Patents & Royalties; Novartis: Patents & Royalties; Roche: Consultancy, Honoraria. Nagumantry: Alexion: Honoraria; Janssen: Honoraria. Shah: Janssen: Consultancy; Abbvie: Consultancy. Cheah: TG Therapeutics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Research Funding; AstraZeneca: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Beigene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Lilly: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; MSD: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. McKay: Abbvie: Consultancy; AstraZeneca: Consultancy; Beigene: Consultancy; Celgene/BMS: Consultancy; Epizyme: Consultancy; Gilead/Kite: Consultancy, Speakers Bureau; Incyte: Consultancy, Speakers Bureau; Janssen: Consultancy, Speakers Bureau; Recordati Rare Diseases: Consultancy; Roche: Consultancy; Takeda: Consultancy. Dickinson: Roche, BMS, Novartis, Kite, Gilead, NKARTA, AdiCet Bio, Interius, Janssen, MSD: Consultancy; Roche, BMS, Novartis, Kite, Gilead, NKARTA, AdiCet Bio, Interius, Janssen, MSD, Amgen: Honoraria; Roche, Novartis, Kite, Gilead, MSD, Takeda, Celgene: Research Funding. Seymour: AstraZeneca: Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees; Genor Biopharma: Membership on an entity's Board of Directors or advisory committees; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Celgene: Consultancy, Research Funding, Speakers Bureau; TG Therapeutics: Consultancy; F. Hoffmann-La Roche Ltd: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Follows: Janssen: Honoraria; Abbvie: Honoraria; Roche: Honoraria; Astra Zeneca: Honoraria.

*signifies non-member of ASH