Type: Oral
Session: 624. Hodgkin Lymphomas: Clinical and Epidemiological: Potentially Practice-Changing Trials in Hodgkin Lymphoma
Hematology Disease Topics & Pathways:
Hodgkin lymphoma, Combination therapy, Research, Lymphomas, Clinical Research, Diseases, Treatment Considerations, Lymphoid Malignancies, Adverse Events
Methods: All patients (pts) aged 17-70 years (y) with radioencompassable, limited stage cHL (stage IA, IB, IIA, non-bulky [<10 cm], +/- extranodal extension) diagnosed December 2011-June 2022, an era where staging PET scans were available, and planned for curative intent treatment with ABVD were identified. PET scans performed 2011-2014 were evaluated based on the International Harmonization Project and were retrospectively re-reviewed by the Deauville (D) criteria (D1-2, DX = negative, D3-5 = positive). All pts received ABVD x 2 and those with a positive PET2 (PET2 pos) were switched to radiotherapy (RT). If PET2 neg, pts were recommended to receive a further ABVD x 2 (‘ABVD era’) or AVD x 2 after the policy change (‘AVD era’), for a total of 4 cycles. An era-to-era outcome comparison and a secondary analysis comparing outcomes in the as-treated PET2 neg groups (ABVD4 vs. ABVD2/AVD2) were performed. Bleomycin pulmonary toxicity was determined by the treating physician based on clinical and radiographic features, resulting in permanent bleomycin discontinuation +/- steroid treatment.
Results: 188 pts were identified, 69 in the ABVD era, 119 the AVD era. Median age 34 y (range 17-68), 22 (12%) were age ≥60, 98 (52%) females, 34 (18%) stage I. The median size of the largest mass was 4 cm (range 1-9 cm). The majority of pts (179, 95%) had a staging PET. Overall, 17 (9%) pts received RT at a similar frequency between eras (p=0.30).
159/188 pts (85%) were managed per policy recommendation with all deviations in the later era. Two pts did not have PET2, 1 was planned for combined modality therapy and 1 non-compliant. For the remaining 27 pts, 19 continued ABVD with PET2 neg and 5 continued chemotherapy following PET2 D3 by physician discretion. The remaining 3 pts had individual treatment modifications. Median follow-up for alive pts was 73 months (range 15-149), 122 months (range 15-149) in the ABVD era, 59 months (range 26-101) in the AVD era. For all pts, the 5-year (5 y) PFS was 93.8%, and 5 y OS was 99.3% with only 1 death due to cHL.
There was no difference in age ≥60 y (p=0.93), sex (p=0.57), stage (p=0.40), or mass size ≥5 cm (p=0.94) distribution across the two eras. In the era-to-era (ABVD era vs. AVD era) comparison (n=188), outcomes were similar: 5 y PFS 92.3% vs. 94.9% (p=0.504), 5 y OS 98.4% vs. 100% (p=0.220). In total, 15 pts (8%) were determined to have bleomycin toxicity: 11 (16%) in the ABVD era, 9 (82%) during cycle 3 or 4, while only 4 (3%) had pulmonary toxicity in the AVD era, all during cycle 2 of ABVD (p=0.001). The median age was 55.5 y for all pts with pulmonary toxicity during cycle 2 (3.2%).
163/186 pts (88%) had a PET2 neg scan. All but 2 completed treatment with chemotherapy alone, with 158 (97%) completing 4 cycles. Two PET2 neg pts switched to RT due to poor chemotherapy tolerance. The remaining 23 (12%) were PET2 pos; 14 (61%) switched to RT as planned, and the remainder completed treatment with 2 further cycles of chemotherapy by physician choice. PET2 response status was unaltered with D score re-review. By PET2 status, 5 y PFS was 95% for PET2 neg, with no difference by D score (p=0.33) and 82% for PET2 pos pts (p=0.15).
In an as-treated analysis of PET2 neg pts who completed treatment with either ABVD x 2 (n=65) or AVD x 2 (n=96) in both eras, there was no difference in baseline clinical features. There further was no difference in PFS (5 y 91.2% vs. 95.9%, p=0.39) or OS (5 y 98.4% vs. 100%, p=0.998) in the ABVD and AVD groups, respectively. In total, 6 pts (9%) in the PET2 neg ABVD group relapsed, 4 at the original disease site and 2 pts (3%) died, 1 from cHL. Four pts (4%) in the PET2 neg AVD group relapsed, all at the original site, and 1 pt died due to cardiac cause.
Conclusion: Omission of bleomycin for cycles 3 and 4 in limited stage cHL following a PET2 neg scan (D1-2, DX), preserves excellent outcomes and may reduce the incidence of pulmonary toxicity. Rare pulmonary toxicity can occur during cycle 2 of ABVD and with older adults at risk, omission of bleomycin for all cycles should be strongly considered.
Disclosures: Villa: Merck, Abbvie, Roche, AstraZeneca, BeiGene, Janssen, BMS/Celgene, Kite/Gilead, InCyte: Consultancy; Roche, AstraZeneca: Research Funding; Merck, Abbvie, Roche, AstraZeneca, BeiGene, Janssen, BMS/Celgene, Kite/Gilead, InCyte: Honoraria. Gerrie: AstraZeneca, Beigene, Janssen, Lilly: Research Funding; AstraZeneca, Beigene, Janssen, Lily, Celgene: Honoraria. Venner: Janssen, BMS, GSK, Sanofi, Pfizer, Abbvie, Forus: Honoraria. Scott: Roche: Consultancy, Honoraria; AstraZenenca: Consultancy, Honoraria; Genmab: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Roche/Genentech: Research Funding; Veracyte: Consultancy, Honoraria; Nanostring: Patents & Royalties: use of gene expresssion to subtype aggressive lymphoma. Sehn: Roche, Seattle Genetics: Speakers Bureau; AbbVie, Acerta, Apobiologix, AstraZeneca, Celgene, Debiopharm, Genentech, Genmab, Gilead Sciences, Incyte Corporation, Janssen, Karyopharm Therapeutics, Kite Pharma, Lundbeck, Merck, MorphoSys, Novartis, Sandoz, Takeda, TG Therapeutics, Verastem Oncology: Membership on an entity's Board of Directors or advisory committees; Teva: Other: Research Grants; F. Hoffmann-La Roche Ltd; Genentech, Inc.; Teva: Research Funding; AbbVie; Amgen; AstraZeneca; Beigene; BMS/Celgene; Genmab; Kite/Gilead; Incyte; Janssen; Merck; Seagen; F. Hoffmann-La Roche Ltd; Genentech, Inc.: Honoraria; AbbVie; Amgen; AstraZeneca; Beigene; BMS/Celgene; Genmab; Kite/Gilead; Incyte; Janssen; Merck; Seagen; F. Hoffmann-La Roche Ltd; Genentech, Inc.: Consultancy. Savage: Regeneron: Other: DSMC; Seagen: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy; Bristol Myers Squibb: Consultancy, Research Funding.