Autologous and Allogeneic Stem Cell Transplantation for Major T-Cell Lymphoma Entities: An Analysis of the EBMT Lymphoma Working Party

Background:

There is a paucity of large-scale and long-term outcome data of autologous- and allogeneic stem cell transplantation (auto-; allo-SCT) for the major T-cell entities, differentiating between patients (pts) treated for consolidation or relapsed/refractory disease (r/r) and between entities. Therefore, we analyzed auto- and allo-SCT activities registered with EBMT and co-operating Asian centers between 2002 and 2022.

Methods:

Pts meeting the following criteria were included: age≥18 years (yrs), diagnosis of peripheral T-cell lymphoma not otherwise specified (PTCL NOS), angioimmunoblastic T-cell lymphoma (AITL), and anaplastic lymphoma kinase (ALK)-negative (ALK-), and ALK+ anaplastic large cell lymphoma (ALCL), auto-SCT as first SCT or allo-SCT either as first SCT or after auto-SCT. For the subgroup analyses (front-line vs salvage), we focused on the time period between 2016 and 2022 acknowledging the improved data quality.

Results:

In total, 7108 pts received auto-SCT and 1292 pts allo-SCT between 2002 and 2022. Diagnosis was PTCL NOS (n=3359 vs n=670), AITL (n=2412 vs n=426), ALK- ALCL (n=994 vs n=109), and ALK+ ALCL (n=343 vs n=87), respectively.

With a median follow-up of 3.3 and 3.9 yrs for all entities, 5-yr progression-free survival (PFS) for PTCL NOS, AITL, ALK- and ALK+ ALCL after auto-SCT was 37.5%, 37.2%, 57.6%, 57.5%, respectively (p<0.001), and after allo-SCT 41.6%, 51.1%, 40.1%, 62.3%, respectively (p<0.001). 5-yr overall survival (OS) was 53.1%, 54.4%, 72.9%, 80.2%, respectively after auto-SCT (p<0.001) and 47.2%, 53.8%, 47.9%, 79.9%, respectively (p<0.001) after allo-SCT. The 5-yr relapse incidence (RI) and non-relapse mortality (NRM) were 52.3% and 7%, respectively for auto-SCT, and 27.4% and 26.5%, respectively for allo-SCT.

Of all pts, 2578 underwent auto-SCT and 332 directly allo-SCT between 2016 and 2022 while 427 of auto-SCT pts (16.6%) received allo-SCT subsequently.

Auto-SCT pts transplanted in first CR (CR1) and second CR (CR2) showed superior outcomes compared to pts treated in first PR (PR1) and progressive disease (PD) [2-yr PFS 62.9% vs. 54.8% vs 47.4% vs 32.5%, p<0.001; 2-yr OS: 80.7% vs 71.8% vs 69.4% vs 52%, p<0.001]. This trend was also documented across distinct entities. 2-yr PFS in PTCL NOS, AITL and ALK- ALCL was as following: CR1 (60.3%/56.8%/76.6%, p<0.001), CR2 (52%/44.6%/69.7%, p<0.001), PR1 (42.4%/45.6%/58.4%, p=0.01), and PD (26.9%/33.2%/49.5%, p=0.75); and 2-yr OS CR1 (75.4%/79.2%/91%, p≤0.001), CR2 (67.5%/66%/83.7%, p≤0.001), PR1 (60.8%/70.8%/79.1%, p=0.03), and PD (50.5%/58.6%/52.5%, p=0.75), respectively. Pts undergoing auto-SCT in first-line (1L) vs 2L vs 3L+ had better survival results in 1L: 2-yr PFS 58.5% vs 49% vs 41.5%, p<0.001; 2-yr OS: 77.1% vs 65.5% vs 63%, p<0.001, accordingly. The 2-yr RI post-auto-SCT for CR1, CR2, PR1, and PD was 32.6%, 41%, 50%, and 56.8% (p<0.001).

In the allo-SCT group, outcomes in CR1/PR1, CR2 and PD pts were as follows: 2-yr PFS: 65% vs 64.9% vs 39.7% (p<0.001); 2-yr OS: 68.8% vs 71.3% vs 37.8% (p<0.001). Considering distinct entities, 2-yr PFS and 2-yr OS in PTCL, AITL and ALK- ALCL were: 2-yr PFS CR1/PR1 pts (68.2%/61.8%/61.7%, p=0.79), CR2 (55.7%/71%/67.6%, p=0.19) and PD (40.3%/41.7%/33.3, p=0.54); 2-yr OS CR1/PR1 (68.2%/64.3%/79.5, p=0.87), CR2 (66.1%/73.5%/76.5%, p=0.52) and PD (38.1%/41.4%/29.6%, p=0.4), respectively. Notably, the survival after allo-SCT was similar following 1L, 2L and 3L+ (2 yr PFS 56.1-65.1%, p=0.56; 2 yr OS 59.3-68.6%, p=0.22). The 2-yr RI post-allo-SCT for CR1/PR1, CR2 and PD was 15.6%, 16% and 35.6% (p=0.003) while 2-yr NRM was without significant differences (19.4%-24.7%, p=0.48).

Conclusion:

In the major T-cell entities, transplantation resulted in excellent long-term survival after auto- or allo-SCT. Auto-SCT in CR1/CR2 resulted in the best survival. Outcomes post-auto-SCT differed significantly among entities; further analyses therefore should report auto-SCT results separately for each entity. In contrast, outcomes after allo-SCT were determined by disease status before transplantation but not by the number of prior therapies or the specific entity probably reflecting the “equalizing” properties of the graft vs lymphoma effect. This analysis does not allow a direct comparison of auto- and allo-SCT; taking into account the efficacy and toxicity data, auto-SCT works best in early CR pts while allo-SCT should be strongly considered for all other pts.

Shumilov:Oncopeptides: Consultancy, Honoraria, Other: Travel and congress support; Incyte: Honoraria; BMS: Consultancy, Honoraria; Gilead: Consultancy, Honoraria, Other: Travel and congress support; Pfizer: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Other: Travel and congress support; Stemline: Consultancy, Honoraria; Sanofi-Aventis: Consultancy, Honoraria, Other: Congress support. Carpenter:Vertex Pharmaceuticals Incorporated: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Bluebird Biotech: Honoraria. Zeiser:Sanofi: Honoraria; Mallinkrodt: Consultancy, Honoraria; Neovii: Consultancy; Medac: Honoraria; Incyte: Consultancy, Honoraria; Ironwood Pharmaceuticals, Inc.: Consultancy; Novartis: Consultancy, Honoraria. Nur:Novartis: Research Funding; Vertex: Speakers Bureau. Mielke:Celgene/BMS; Novartis; Janssen; Pfizer: Speakers Bureau; Gilead/KITE: Other: travel support, expert panel; Immunicum/Mendes; Miltenyi: Other: DSMB; SWECARNET: Other. Nicholson:Kite/Gilead: Honoraria, Research Funding; Novartis: Honoraria; BMS/Celgene: Honoraria; Autolus: Membership on an entity's Board of Directors or advisory committees. Lenz:AGIOS: Research Funding; AQUINOX: Research Funding; Gilead: Honoraria, Research Funding; BMS: Honoraria; Constellation: Honoraria; Genase: Honoraria; Genmab: Honoraria; Hexal/Sandoz: Honoraria; Immagene: Honoraria; Incyte: Honoraria; Karyopharm: Honoraria; Lilly: Honoraria; Miltenyi Biotech: Honoraria; MSD: Honoraria; NanoString: Honoraria; PentixaPharm: Honoraria; Pierre Fabre: Honoraria; Sobi: Honoraria, Speakers Bureau; Acerta: Research Funding; Roche, Gilead, BMS, Novartis, AstraZeneca, Abbvie, Incyte, Genmab, Constellation, ADC Therapeutics, Miltenyi, PentixaPharm, Sobi, Immagene, Genase, Hexal-Sandoz, Lilly, Beigene, MSD, Pierre Fabre: Consultancy; ELVESCA: Current equity holder in private company; Roche, Gilead, BMS, Novartis, AstraZeneca, Abbvie, Incyte, Genmab, Constellation, ADC Therapeutics, Miltenyi, PentixaPharm, Sobi, Immagene, Genase, Hexal-Sandoz, Lilly, Beigene, MSD, Pierre Fabre: Membership on an entity's Board of Directors or advisory committees; AbbVie, BeiGene, Sobi, Roche, Gilead, BMS: Other: Travel; MorphoSys: Honoraria, Research Funding; BeiGene: Honoraria; Amgen: Honoraria; AbbVie: Honoraria; ADC Therapeutics: Honoraria; Verastem: Research Funding; Roche: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Bayer: Honoraria, Research Funding; AstraZeneca: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Celgene: Honoraria, Research Funding. Sureda Balari:BMS/Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Expenses, Research Funding, Speakers Bureau; Takeda Pharmaceutical: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Expenses, Research Funding, Speakers Bureau; GETH-TC: Other: President; EBMT: Other: President; GSK: Consultancy, Honoraria, Speakers Bureau; Mundipharma: Consultancy; Alexion: Honoraria; MSD: Consultancy, Honoraria, Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead Kite: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Honoraria, Other: Travel Expenses; Bluebird: Membership on an entity's Board of Directors or advisory committees. Glass:Roche, Kite Gilead, BMS: Other: travel support ; Riemser, Roche: Other: grants ; Kite Gilead, Novartis, BMS, Roche, Miltenyi, Incyte: Honoraria. Bazarbachi:Pfizer: Research Funding; Biologix: Research Funding; Amgen: Honoraria; Caribou: Honoraria; Takeda: Honoraria; Jansen: Honoraria, Research Funding; Roche: Honoraria, Research Funding. Schmitz:Janssen: Research Funding; Beigene: Other: travel grant; Roche: Honoraria, Other: travel grant; Astra Zeneca: Research Funding; Abbvie: Research Funding; BMS: Current equity holder in publicly-traded company.