Autologous and allogeneic stem cell transplantation for ALK-positive anaplastic large cell lymphoma: An analysis of the EBMT lymphoma working party

Abstract Background Adults with anaplastic lymphoma kinase-positive anaplastic large cell lymphoma (ALK-pos. ALCL) treated with CHOP or variants have a significantly better prognosis than patients (pts) with other major T-cell entities. Accordingly, the experience with autologous (ASCT) and allogeneic transplantation (allo-SCT) in such pts is limited. Methods: We analyzed major outcomes of pts >18 years diagnosed with ALK-pos. ALCL and registered with EBMT and co-operating Asian centers between 2010 and 2022. Because of the large patient numbers we were able to separately analyze pts transplanted up-front and for relapsed/ refractory (r/r) disease. Results: In total, 282 pts underwent ASCT (up-front n=81; salvage n=201) and 77 pts salvage allo-SCT (median age 40 and 31 years, respectively). In pts given up-front ASCT, 69% had IPI ≥ 3 at diagnosis. Brentuximab vedotin (BV)-containing therapy before up-front ASCT, salvage ASCT, and allo-SCT had been administered to 25.9%, 24.4%, and 28.6% respectively. Among pts who underwent salvage ASCT, 70% pts received 2 and 30% received 3 therapy lines prior to transplantation. In the salvage allo-SCT group, 48% had 2 and 52% had 3 therapy lines prior to transplantation. The majority of patients undergoing salvage ASCT or allo-SCT had chemo-sensitive disease (CR/PR) (94.5% vs. 90.9%) prior to transplantation. Particularly, 75.1% and 70.2% had second complete remission or later (CR2+) at salvage auto- and allo-SCT, accordingly. Seventeen % of pts relapsing after ASCT subsequently received allo-SCT. With a median follow-up of 2 years, 2-yr progression-free survival (PFS) and overall survival (OS) were 79.2% and 91.3% after up-front ASCT and 59.7% (p=0.016) and 83.9% (p=0.72) after salvage ASCT. 2-yr relapse incidence (RI) and non-relapse mortality (NRM) were 18.1% and 36.8% (p=0.012), and 2.6% and 3.4% (p=0.09), respectively, for up-front and salvage ASCT. Patients consolidated with up-front ASCT in first CR (CR1) or first PR (PR1) did not show statistically different PFS (p=0.78), OS (p=0.309), RI (p=0.94) or NRM (p=0.43). A trend for higher NRM (9.2% vs. 2.3%; p=0.06) was documented in pts in second PR (PR2) or later (PR2+) as compared to CR2+ pts. OS (80.8% vs. 87.8%; p=0.45), PFS (both 61%), and RI (29.3% vs. 36.1%; p=0.4) did not differ significantly. For pts undergoing allo-SCT median follow-up was 3.3 years (yr) and 3-yr PFS 66.2%; 3-yr OS 78.5%, RI 24.1%; and NRM 9.6%. Three-yr PFS and -OS were 69.4% and 85% for pts allografted in CR2+ and 77.3% and 77.3% for pts allografted in PR2+. None of these differences were significantly different statistically. Notably, survival after allo-SCT was better in 2L than in 3L+ (3-yr PFS 82.4 vs. 52.7%, p=0.008; 3-yr OS 84.7% vs. 73.2%, p=0.24) due to lower RI (8.9% vs. 36.7%; p=0.007) while NRM was comparable (8.6% vs. 10.6%; p=0.81). The 3-yr RI post-allo-SCT for CR2+/PR2+/stable and progressive disease (SD/PD) were 21.9%, 14.1% and 57.1% (p=0.08) while 3-yr NRM was 8.7%, 8.6% and 14.3% (p=0.773). Conclusion: In ALK-pos. ALCL, ASCT and allo-SCT resulted in excellent long-term survival. Optimal results were observed for ASCT administered for consolidation in first remission or r/r disease for chemosensitive disease (CR/PR). In such pts, allo-SCT can be reserved for pts relapsing after ASCT. All other pts should be considered candidates for allo-SCT with excellent outcomes recorded for pts who predominantly were in CR prior to allo-SCT.