Outcomes in pediatric relapsed/refractory anaplastic large cell lymphoma: A multi-institutional retrospective analysis.

Lianna Jean Marks Stanford University School of Medicine, Palo Alto, CA info_outline Lianna Jean Marks, Victor Ritter, Liora M. Schultz, Eric J. Lowe, Catherine Aftandilian

Authors Lianna Jean Marks Stanford University School of Medicine, Palo Alto, CA info_outline Lianna Jean Marks, Victor Ritter, Liora M. Schultz, Eric J. Lowe, Catherine Aftandilian Organizations Stanford University School of Medicine, Palo Alto, CA, Children's Hospital of The King's Daughters Surgical Group, Norfolk, VA Abstract Disclosures Research Funding Other Stanford Maternal & Child Health Research Institute Award Background: Treatment options for relapsed or refractory (R/R) anaplastic large cell lymphoma (ALCL) have increased in the era of targeted therapies such as brentuximab vedotin (BV) and Anaplastic Lymphoma Kinase (ALK)-inhibitors. However, there is no standard treatment and limited published data evaluating their use in this patient population. Methods: We conducted a retrospective, multi-institutional study of patients <22 yrs old at initial diagnosis with R/R ALCL treated between 2011-2021 across 18 institutions. Results: We identified 85 patients with R/R ALCL (median age at initial diagnosis 12 yrs, 67% male, 96% ALK+). Treatment for initial diagnosis included ALCL99 (31%), ANHL12P1 + BV (32%), ANHL12P1 + crizotinib (CZ) (11%), ANHL0131 (14%), or other (13%). Median time from diagnosis to relapse was 0.7 yrs (range 0.2-10.8 yrs) with sixteen patients (18%) relapsing on initial chemotherapy. Stage at relapse for 82 ALK+ patients: I (9%), II (15%), III (41%), IV (35%). Initial re-induction regimens shown in the table. Fifty-nine (72%) patients received a hematopoietic stem cell transplant (HSCT), 11 autologous and 49 allogeneic with one receiving both. Of 59 transplanted patients, 10 relapsed (6 allo 4 auto) and 7 died. All but one of the patients who relapsed post-HSCT responded to additional therapy and remain alive. Of 23 ALK+ patients who never had a transplant, 4 patients died and 19 are alive in remission. Eleven remain on active therapy (6 CZ, 3 BV, 1 BV+CZ, 1 vinblastine) with eight off therapy. Patients who received a transplant more likely to be off therapy and alive. Duration of treatment for patients receiving BV or the ALK-inhibitor CZ varied widely (BV 1-11 yrs; CZ 2-10 yrs) with 20 patients continuing on therapy at the time of data collection. Five-year overall survival for patients with or without transplant was 91% (CI 84-99%) and 86% (CI 73-100%) respectively. Conclusions: This is the largest collection of patients with R/R ALK+ ALCL treated in the era of targeted therapy. Patients achieved excellent responses to ALK-inhibitor or BV monotherapy, but questions remain about duration of therapy. Transplant may not be necessary for all R/R patients including those with high-risk disease. Characteristic Overall N = 82 Not transplanted N = 23 Transplanted N = 59 Time to first relapse in yrs, Median (IQR) 0.7 (0.5 – 1.2) 0.8 (0.5 – 2.0) 0.7 (0.5 – 1.1) First re-induction regimen, n (%) ALK-inhibitor Brentuximab Chemo Chemo + Targeted Vinblastine - 39 (48) 17 (21) 13 (16) 9 (11) 4 (4.9) - 11 (48) 5 (22) 4 (17) 2 (8.7) 1 (4.3) - 28 (47) 12 (20) 9 (15) 7 (12) 3 (5.1) Achieved CR, n (%) 76 (93) 19 (83) 57 (97) Second relapse, n (%) 14 (17) 4 (17) 10 (17) Treatment outcome, n (%) Alive off Alive on Dead - 51 (62) 20 (24) 11 (13) - 8 (35) 11 (48) 4 (17) - 43 (73) 9 (15) 7 (12) Death, n (%) Death due to ALCL progression Death due to treatment toxicity Death due to other cause - 4 (4.9) 4 (4.9) 3 (3.7) - 3 (13) 0 (0) 1 (4.3) - 1 (1.7) 4 (6.8) 2 (3.4)