ANIMATE: A UK PHASE II PET RESPONSE-ADAPTED TRIAL of NIVOLUMAB in RELAPSED / REFRACTORY CLASSICAL HODGKIN LYMPHOMA.
No Thumbnail Available
All Authors
Collins, G.
Kirkwood, A.
Tyson, C.
Lawrie, E.
Clifton-Hadley, L.
Miall, F.
Ledieu, R.
Phillips, E.
Osborne, W.
Culligan, D.
LTHT Author
Burton, Cathy
LTHT Department
Oncology
Haematology
Haematology
Non Medic
Publication Date
2024
Item Type
Conference Abstract
Language
Subject
ADULT , DRUG-RELATED SIDE EFFECTS AND ADVERSE REACTIONS , HODGKIN DISEASE , COHORT STUDIES , DRUG THERAPY, COMBINATION , DRUG THERAPY , DISEASE-FREE SURVIVAL , WOMEN , FOLLOW-UP-STUDIES , ECONOMICS , HYPERTHYROIDISM , MEN , NEUTROPHILS , SURVIVAL RATE , CHEMOTHERAPY , CLINICAL TRIALS AS TOPIC , POSITRON EMISSION TOMOGRAPHY COMPUTED TOMOGRAPHY , RECURRENCE , UVEITIS , ANTIBODIES , IMMUNOTHERAPY
Subject Headings
Abstract
Background: Relapsed classical Hodgkin Lymphoma (rCHL) is treated with curative intent using chemotherapy aiming for complete metabolic response (CMR) followed by autologous stem cell transplant (ASCT) in suitable patients. Aim(s): The ANIMATE trial was designed to assess the response to single agent nivolumab (a programmed death-1 inhibitor, PD1i) in ASCT-fit patients failing to achieve CMR to 1st or 2nd line relapse treatment. Method(s): Adults with rCHL undergoing 1st or 2nd line relapse therapy were registered. Centrally reviewed FDG-PET-CT was performed (PET0) after 2 cycles (or 4 for Brentuximab vedotin, BV). Patients achieving CMR (Deauville 1-3, PET0-) received standard of care. Patients with Deauville 4-5 (PET0+) received 4 cycles of nivolumab 240mg every 2 weeks. Patients with subsequent CMR or progressive disease (PD) stopped treatment and all others continued with 4 further doses. The primary endpoint was overall response (OR) to 4-8 cycles. Assuming an OR of 60%, seeking to exclude a rate <= 40%, 30 patients with >= 16 responses were required (1-sided alpha 0.1, 80% power). Secondary endpoints included: overall survival (OS), progression free survival (PFS), the proportion receiving SCT and safety. Result(s): 78 eligible patients were registered. Initial treatment was A(B)VD in 60%; 10% having received escalated BEACOPP/BEACOPDac. 38% had primary refractory disease. The most frequently used 1st line relapse regimen was GDP in 57% followed by ifosfamide containing regimens (IGEV and IVE) in 31%. The CMR rate to the 3 most commonly used 1st line regimens was: GDP 20/44 (45.5%), IGEV 5/11 (45.5%) and IVE 8/11 (72.7%). 11 participants were registered during 2nd line relapse treatment with BV +/-bendamustine the most common regimen (70%). 76 had a per protocol PET0, 50% were PET0+. 31 were given nivolumab, median age 33 years, 58% male and 13% post 2nd line relapse treatment. Thirteen patients had CMR or partial metabolic response to nivolumab: OR 41.9% (80% CI: 29.7-55.0; CMR 25.8%) With 29 months median follow-up: 2y PFS was 66.2% (Figure; 95% CI: 45.9-80.3). Partly due to the strict definition of progression, eleven patients with inadequate response received further treatment pre-PD giving 2y failure free survival rate of 38.1%. 25/31 nivolumab treated patients received SCT, 15 ASCT (no PFS events; median FU from SCT 22.1 months) and 10 allogeneic (3 PFS events; 29.7 months). The 2y OS was 91.9% for all registered; 94.6%/87.4% in the PET0-/PET0+ groups (nivolumab cohort: 90.0%). 6/78 registered patients died; 3 in the nivolumab cohort, all post PD. Of 10 patients receiving chemotherapy/BV after nivolumab, with response assessment available, 6 achieved CMR. Of 4 patients refractory to all prior chemotherapy, 2 achieved CMR and one PMR to post-nivolumab chemotherapy. 28% of patients experienced grade 3 adverse events (no grade 4-5), the most common being neutropenia and line infection (6% grade 3 each). 3 experienced immune related reactions: 1 grade 2 uveitis and 2 reports of grade 1 hyperthyroidism. Summary/Conclusion: In the 2nd or 3rd line relapse setting in ASCT-fit patients, the primary endpoint was not met and OR lower than reported in other studies suggesting single agent PD1 inhibition may not be an optimal strategy. However a 2y OS of 90% was encouraging. This may in part be caused by high response rates to treatment post nivolumab, even in patients who had failed to respond to any previous line, suggesting a possible chemosensitising effect. Nivolumab was well tolerated with no high grade immune related reactions. Further work is needed to optimise outcomes in this setting but these data support PD1 inhibition as an important component of the rCHL treatment pathway. Although non-randomised, our data showed highest response rates to IVE as 1st relapse chemotherapy. (Figure present).
Journal
HemaSphere