Huntsman Cancer Institute-University of Utah, Salt Lake City, UT
Charlotte Burton Wagner , Daniel Arthur Ermann , Kenneth M. Boucher , Adrienne Nedved , Ivana N. M. Micallef , Haris Hatic , Gaurav Goyal , Erin Hickey , Amanda Fegley , Courtney Samuels , Manali K. Kamdar , Sheeba Habeeb Ba Aqeel , Pallawi Torka , Kira MacDougall , Azra Borogovac , Sridevi Rajeeve , Kalub Fedak , Elizabeth Travers , Harsh Shah
Background: The AETHERA trial demonstrated improvement in PFS with 16 cycles of brentuximab vedotin (BV) after autologous stem cell transplant (ASCT) in BV-naive patients with high-risk relapsed/refractory classical Hodgkin lymphoma (r/r cHL). However, in real world, patients are rarely able to complete all 16 cycles of BV at full dose. We performed a multicenter retrospective study to assess the impact of cumulative dose on toxicity and 2-year PFS. Methods: Patients from 11 institutions across the US who had received at least one cycle of BV maintenance after ASCT for r/r cHL with one of these features were included: primary refractory disease (PRD), extra-nodal disease (END), or relapse < 12 months of diagnosis (RL<12). PFS was compared between the three cohorts based on a total cumulative dose of 28.8 mg/kg (1.8 mg/kg x 16 cycles): C1, those that received >75% (21.7 to 28.8 mg/kg) cumulative dose of BV, C2, those that received between 51% -75% (14.5 to 21.6 mg/kg) dose and C3, those that received ≤ 50% (≤ 14.4 mg/kg) dose. Results: Between July 2015-June 2019, 100 patients with a median age of 34 years (19-70) underwent ASCT for r/r cHL. At relapse, 44% had PRD, 47% had RL<12, 39% had END and 45% had received BV as initial (1%) or salvage (44%) therapy. 71% had CR before ASCT and 23% received >1 line of salvage (>1 SLT). There was no difference in baseline characteristics between the cohorts. Thirty-six patients were in C1, 27 in C2, and 37 in C3. Only 14% of patients received full cumulative dose of BV. The median number of cycles completed was 12. Fifty-seven patients discontinued early: 39 for toxicity, 7 for progression, 5 for patient preference, 2 for cost and 4 for other reasons. Six of the patients who stopped early for progression were in C3. Grade ≥3 adverse events for neuropathy, neutropenia, and infections were 16%, 7%, and 5% respectively. There was no difference in severity of neuropathy in patients who had received BV prior to ASCT (p=.37). The median follow up was 3.37 years (.4–6.35). The 2-year PFS was 85% for all subjects, 94% for C1, 84% for C2, and 72% for C3 (p=.079) (Table). Patients in C3 had worse PFS compared to C1 (p=.035); this difference remained significant after adjusting for five other factors. There was no difference in PFS between C1 and C2 (p=.29). Conclusions: The majority of patients discontinued BV maintenance early due to toxicity. 2-year PFS was robust regardless of cumulative dose of BV. We conclude that total cumulative dose of 28.8 mg/kg of BV maintenance is not necessary and 51%-75% of total BV dose may still attain a similar PFS advantage.
Patient cohort | N | 2-year PFS (95% CI) | P-value, unadj. | P-value, adj for PRD, CR before ASCT, RL<12, >1 SLT, Prior BV |
---|---|---|---|---|
All | 100 | 0.85 (0.77-0.92) | --- | --- |
C1 | 36 | 0.94 (0.87-1.00) | Ref. | Ref |
C2 | 27 | 0.84 (0.71-1.00) | 0.29 | 0.22 |
C3 | 37 | 0.72 (0.59-0.88) | 0.035 | 0.024 |
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