SINGLE AGENT BRENTUXIMAB VEDOTIN AS BRIDGE TO ALLOGENEIC STEM CELL TRANSPLANT IN ADOLESCENTS WITH RELAPSED ANAPLASTIC LARGE CELL LYMPHOMA (ALCL): THE UCLH EXPERIENCE

Abstract

Introduction: Optimal treatment for relapsed ALCL in children and adolescents is still subject of debate. We present here the results of our salvage strategy in the TYA Unit at UCLH, using single agent brentuximab vedotin (BV) as bridge to allogeneic stem cell transplant (alloHSCT). Methods: Between 2011 and 2021 we treated 7 patients with relapsed ALCL; all patients had received first line treatment according to ALCL99 guidelines. All relapses were biopsy proven and centrally reviewed if not performed at UCLH. Brentuximab Vedotin was given at the standard dose of 1.8mg/kg intravenously every 3 weeks. Results: All 7 patients were male; median age at diagnosis was 16 (range 13–19). Baseline characteristics were as follows: 7/7 were CD30+, 3/7 were CD3+, 6/7 biopsies were ALK positive, and 3/7 presented with a small cell/lymphohistiocitic (SC/LH) pattern. Six/7 patients had stage IV disease, 4/7 had skin involvement, bone marrow involvement was seen in 3/7 cases (infiltrate between 2 and 10%); 1/7 patients had bulky disease. Of the 7 patients, 3 had primary progressive disease, while 4/7 patients initially achieved a complete metabolic response (CMR), but had a very early relapse, between 2 and 3 months after completion of treatment. 6/7 patients received BV as first line of salvage treatment, 1 as second salvage, after failing ICM (ifosfamide, carboplatin, mitoxantrone), which was still our standard of care in 2011. Median number of doses of BV received was 3 (range 2–5); 6/7 (86%) patients obtained a complete metabolic remission, after a median of 3 doses (range 3–5). One patient progressed on BV; after failing crizotinib he achieved CMR with vinblastine-dexamethasone, then proceeded to transplant and is in long term remission. All 6 patients who achieved a complete remission after BV proceeded to alloHSCT, 1/6 from fully matched sibling donor, 3/6 from haploidentical donors, 2/6 from matched unrelated donors. Conditioning regimen was myeloablative for 5/6 patients, using Cyclophosphamide/total body irradiation +/- Campath depending on donor source; one patient received intermediate intensity conditioning with BEAM (BCNU, etoposide, cytarabine, melphalan)-Campath. With a median follow up of 55 months (range 4–133), all 6 patients are alive and 5/6 (83%) remain in remission with no need for further treatment; 1/6 patients relapsed 8 months post-transplant. This patient was re-challenged with BV, with the addition of donor lymphocytes infusions (DLI) and achieved a complete remission. Conclusions: Salvage treatment with single agent BV followed by alloHSCT is effective in adolescents with relapsed ALCL and lead to durable responses in a cohort of patients with high prevalence of high-risk features (advanced stage, SC/LH pattern, CD3+, early relapse after first line treatment). Interestingly, in one patient who relapsed after alloHSCT, BV and DLI were successful in inducing another complete remission. Keywords: Molecular Targeted Therapies, Non-Hodgkin (Pediatric, Adolescent, and Young Adult), Stem Cell Transplant No conflicts of interests pertinent to the abstract.