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877 Real World Escalated Beacopdac Delivers Similar Outcomes to Escalated Beacopp and Superior Outcomes to Response-Adapted (RATHL) ABVD, While Potentially Reducing Toxicity Compared with Escalated BeacoppClinically Relevant Abstract

Program: Oral and Poster Abstracts
Type: Oral
Session: 624. Hodgkin Lymphomas and T/NK cell Lymphomas: Hodgkin Lymphoma Clinical Outcomes Data
Hematology Disease Topics & Pathways:
Hodgkin Lymphoma, Adults, Lymphomas, Clinical Research, Clinically Relevant, Diseases, Real World Evidence, Lymphoid Malignancies, Young Adults, Study Population
Monday, December 13, 2021: 6:15 PM

Anna Santarsieri1*, Katherine Sturgess, MA, MBBChir, MRCP, MSc1*, Pauline Brice2*, Tobias F Menne, MD, PhD, FRCPath3*, Wendy Osborne, MBBS3*, Thomas Creasey, MBBS3*, Kirit M. Ardeshna, MD, MA, FRCP, FRCPath4, Sarah Behan1*, Kaljit Bhuller5*, Stephen Booth, MA, MBBChir, MRCP, FRCPath6*, Graham P. Collins, MD, DPhil7, Kate Cwynarski4*, Andrew Davies, MD, PhD8*, Michelle Furtado, MD, FRCPath, PhD9*, Eve Gallop-Evans10*, Andrew Hodson, MD11*, Sunil Iyengar, MD, FRCPath, PhD12*, Stephen G Jones13*, Kim Linton14*, Nicolas Martinez-Calle, MD, MSc15*, Pamela McKay16*, Sateesh K Nagumantry17*, Deirdre O'Mahony, MD18, Beth Phillips19*, Neil Phillips20*, John F Rudge, MA, PhD21*, Nimish Shah22*, Gwyneth Stafford1*, Alex Sternberg, MRCP, MRCPath23*, Rachel Trickey10*, Benjamin J Uttenthal1*, Nathasha Wetherall24*, Andrew K McMillan25 and George A Follows1*

1Department of Haematology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom
2APHP, Hôpital Saint-Louis, Hemato-Oncologie, Université de Paris, Paris, France
3Department of Haematology, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom
4Department of Haematology, University College London Hospitals NHS Foundation Trust, London, United Kingdom
5University Hospitals of Leicester NHS Trust, Leicester, United Kingdom
6Department of Haematology, Oxford University Hospitals, Milton Keynes, United Kingdom
7Oxford University Hospitals NHS Foundation Trust, Oxford, ENG, United Kingdom
8NCRI/Cancer Research UK Experimental Cancer Medicines Centre, University of Southampton, Faculty of Medicine, Southampton, United Kingdom
9Royal Cornwall Hospital, Truro, United Kingdom
10Velindre Cancer Centre, Cardiff, United Kingdom
11Haematology, Ipswich Hospital NHS Trust, Ipswich, United Kingdom
12Department of Haemato-Oncology, Royal Marsden Hospital, Sutton, United Kingdom
13Department of Haematology, Sherwood Forest Hospitals NHS Trust, Sutton-in-Ashfield, United Kingdom
14The Christie NHS Foundation Trust and Manchester Cancer Research Centre, Manchester, United Kingdom
15Nottingham University Hospitals NHS Trust, Nottingham, ENG, United Kingdom
16Beatson West of Scotland Cancer Centre, Glasgow, SCO, United Kingdom
17Peterborough City Hospital, Peterborough, GBR
18Department of Oncology, Cork University Hospital, Cork, Cork, IRL
19University of Manchester, Manchester, GBR
20Department of Haematology, Royal Stoke University Hospital, Stoke-on-Trent, United Kingdom
21Department of Earth Sciences, Bullard Laboratories, Cambridge, United Kingdom
22Haematology, Norfolk and Norwich University Hospitals NHS Foundation Trust, Norwich, United Kingdom
23Department of Haematology, Great Western Hospital, Swindon, ENG, United Kingdom
24University Hospital Southampton, Southampton, United Kingdom
25Nottingham University Hospitals NHS Trust, Nottingham, United Kingdom

Background:

In the treatment of advanced Hodgkin lymphoma, it is increasingly common UK practice to modify escalated BEACOPP (eBPP) by removing oral procarbazine and replacing it with intravenous dacarbazine (250mg/m2 D2-3) to reduce haematopoietic stem cell and gonadal toxicity. However, published data of the "escalated BEACOPDac (eBPDac)" regimen are very limited.

Methods:

This is a retrospective study of 225 patients from 20 centres in the UK, Ireland and France who were treated with eBPDac first line for advanced stage Hodgkin Lymphoma. Toxicity outcomes were compared with 58 matched patients treated with eBPP at 4 UK centres and survival outcomes were compared with 2073 eBPP patients in the HD18 trial1 and with 1088 patients aged 18-59y in the RATHL trial2,3. Most eBPDac patients were treated as per HD18 protocol. The 34 patients treated in Paris followed the AHL2011 protocol with two courses of eBPDac given upfront and if iPET2 negative were deescalated to 4 cycles of ABVD.

Toxicity outcomes:

Toxicity was compared between eBPDac patients (n=225; median follow-up 22.1 months) and matched real-world UK eBPP patients (n=58; median follow-up 52.7 months) over the first 4 cycles. eBPP and eBPDac patients were well matched with no significant differences in age (median 23 y vs 26 y), sex, stage (stage 3/4 82% vs 83%) and international prognostic score (IPS 3+ 74% vs 65%). 55% of eBPDac patients received only 4 cycles (vs 12% of eBPP patients; p<0.001) reflecting publication of HD18 trial data. Mean day 8 (D8) ALT was similar between the two regimens. Mean D8 neutrophil count tended to be lower in eBPDac than eBPP patients (2.04 vs 2.45; p=0.072; G-CSF given D9), however it increased to 6.48 in eBPDac patients given GCSF from D4. There were fewer non-elective days of inpatient care for eBPDac compared with eBPP (mean 3.35 vs 5.84; p=0.022), and eBPDac patients received fewer red cell transfusions compared with eBPP patients (mean 1.79 units vs 4.16 units; p<0.001). Women aged <35, who completed ≥4 cycles of eBPDac/eBPP had a similar rate of return of menstrual cycles (eBPP 22/25; eBPDac 41/41), although eBPDac patients appeared to restart menstruation earlier post chemotherapy (mean 4.64 months vs 9.12 months, p=0.0026). However, this could also reflect the higher mean chemotherapy cycle number completed by the eBPP women (5.86 vs 4.60; p<0.001). The use of Goserelin to suppress ovulation varied between centres.

Disease outcomes:

The eBPDac patients (n=225) were younger than the HD18 patients (median age 26 y vs 35 y, p<0.001) and the RATHL patients (median age 26 y vs 31 y). However, they had higher risk disease than HD18 (IPS 4+ 36% vs 16%, p<0.001) and RATHL patients (IPS 3+ 65% vs 33%, p<0.001) and more stage 4 disease than HD18 (66% vs 36%, p<0.001) and RATHL (66% vs 28%, p<0.001). Of the 225 patients who started eBPDac, 77% achieved iPET2 Deauville score (DS) ≤3, similar to RATHL (DS ≤3: 83.7%) and HD18 (DS ≤3: 76%). Of the eBPDac patients, one patient had primary refractory disease, and ten have relapsed at 6 to 36 months. One 56-year-old eBPDac patient with high IPS died with bowel perforation during cycle 1 and one 34-year-old with alcoholic liver disease died 8 months after treatment while still in remission. There have been no lymphoma-related deaths to date.

Figure 1 shows Kaplan-Meier plots for progression-free survival (PFS) and overall survival (OS). The PFS at 22 months (median follow-up) of eBPDac patients was 94.9% (91.7-98.3%) which is similar to HD18 3 year PFS of 92.3% (91.1-93.5%) and appears superior to RATHL 5 year PFS 81.4% (78.9-83.7%). The difference in PFS between eBPDac and RATHL is most marked in IPS3+ patients. The OS rates with all 3 regimens are excellent, with 22 month eBPDac OS estimate of 98.9% (97.4-100%).

Summary/Conclusion:

Accepting the limitations of a retrospective study, we suggest that substituting dacarbazine for procarbazine is unlikely to compromise the efficacy of eBPP and may have some toxicity benefits. Despite the clear preference of clinicians to offer this regimen to high-risk advanced stage patients, with nearly 2 years median follow-up we have observed similar PFS and OS compared to HD18 but superior survival estimates compared with 18-59y RATHL patients, suggesting that eBPDac is highly efficacious for the treatment of Hodgkin lymphoma.

References:

1Borchmann P et al. Lancet 2017; 390:2790-2802

2Johnson P et al. NEJM. 2016; 374:2419-2429

3Russell J et al. Ann Hematol 2021; 100:1049-1058

Disclosures: Brice: MSD: Research Funding; Amgen: Other: Travel/accommodations/expenses; Roche: Other: Travel/accommodations/expenses; Takeda: Research Funding. Menne: Kite/Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel grant, Research Funding, Speakers Bureau; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel grants; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel grants; Astra Zeneca: Research Funding; Jazz: Other: Travel grants; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel grants; Bayer: Other: Travel grants; Kyowa Kirin: Other: Travel grants; Daiichi Sankyo: Honoraria, Membership on an entity's Board of Directors or advisory committees; Atara: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Other: Honoraria for Lectures; Roche: Other: Honoraria for Lectures. Osborne: Roche: Other; Takeda: Other; Pfizer: Other; Servier: Other; Gilead: Other; Novartis: Other; MSD: Other. Ardeshna: Gilead, Beigene, Celegene, Novartis and Roche: Membership on an entity's Board of Directors or advisory committees; Gilead, Beigene, Celegene, Novartis and Roche: Honoraria; Norvartis, BMS, Autolus, ADCT, Pharmocyclics and Jansen: Research Funding. Collins: ADC Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Speakers Bureau; Incyte: Honoraria, Speakers Bureau; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel expenses, Speakers Bureau; Amgen: Research Funding; Celgene: Research Funding; Beigene: Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AstraZeneca: Honoraria, Research Funding. Cwynarski: Adienne, Takeda, Roche, Autolus, KITE, Gilead, Celgene, Atara, Janssenen: Other. Davies: Janssen: Honoraria, Research Funding; Karyopharm Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Acerta Pharma/AstraZeneca: Honoraria, Research Funding; ADC Therapeutics: Honoraria, Research Funding; BioInvent: Research Funding; Incyte: Membership on an entity's Board of Directors or advisory committees; Kite: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel to scientific conferences, Research Funding; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel to scientific conferences, Research Funding. Furtado: Abbvie: Other: Conference support. Gallop-Evans: Takeda: Membership on an entity's Board of Directors or advisory committees; Kyowa-Kirin: Membership on an entity's Board of Directors or advisory committees. Iyengar: Gilead: Membership on an entity's Board of Directors or advisory committees, Other: conference support, Speakers Bureau; Takeda: Membership on an entity's Board of Directors or advisory committees, Other: conference support, Speakers Bureau; Beigene: Membership on an entity's Board of Directors or advisory committees; Abbvie: Other: conference support; Janssen: Other: conference support, Speakers Bureau. Linton: Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Aptitude Health: Honoraria; Hartley Taylor: Honoraria; University of Manchester: Current Employment; Celgene: Research Funding; BeiGene: Research Funding; Genmab: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Martinez-Calle: Abbvie: Other. McKay: Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead: Honoraria, Other: Travel Support; KITE: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Support; Janssen: Honoraria, Other: Travel Support; Beigene: Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS/Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees. Nagumantry: Takeda, Alexion, Abbvie: Other. Shah: Abbvie, Janssen and Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees. Uttenthal: Jazz: Other; Takeda: Other; Roche: Other. McMillan: Pfizer: Research Funding; F. Hoffmann-La Roche Ltd: Consultancy, Honoraria, Speakers Bureau; Amgen: Membership on an entity's Board of Directors or advisory committees; Abvie: Membership on an entity's Board of Directors or advisory committees. Follows: Janssen, Abvie, Roche, AZ: Other.

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