ALK-negative anaplastic large cell lymphoma: features and outcomes of 235 patients from the International T-Cell Project

Abstract

Anaplastic lymphoma kinase–negative anaplastic large cell lymphoma (ALK– ALCL) is an aggressive neoplasm of T-cell/null-cell lineage. The T-Cell Project is a global prospective cohort study that consecutively enrolled patients newly diagnosed with peripheral T-cell lymphoma, registered through a centralized computer database between September 2006 and February 2018. Of 1553 validated cases from 74 sites in 13 countries worldwide, 235 were reported as ALK– ALCL. The median age at diagnosis was 54 years (range, 18-89 years), with a male predominance (62%). Stage III to IV disease was identified in 71% of patients, bulky disease and bone marrow involvement were uncommon, and 66% of patients presented with a low (0-1) International Prognostic Index score. Of all treated patients, 85% received multiagent initial chemotherapy, and 8% were consolidated with autologous hematopoietic cell transplantation. The initial overall and complete response rates were 77% and 63%, respectively. After a median follow-up of 52 months (95% confidence interval [CI], 41-63), the median progression-free survival (PFS) and overall survival (OS) were 41 months (95% CI, 17-62) and 55 months (95% CI, 36-75), respectively. The 3- and 5-year PFS rates were 52% and 43%, and the 3- and 5-year OS rates were 60% and 49%. Treatments containing both anthracycline and etoposide were associated with superior OS (P = .05) but not PFS (P = .18). In this large prospective cohort study, outcomes comparable to those previously reported in the retrospective International Peripheral T-Cell Lymphoma Project were observed. The study underscores the need for introducing novel platforms for ALK– ALCL and establishes a benchmark for future clinical trials. This trial was registered at www.clinicaltrials.gov as #NCT01142674.

Systemic ALCL Treated in Routine Clinical Practice: Outcomes Following First-Line Chemotherapy from a Multicentre Cohort

“…The survival outcomes for our cohort are comparable to data from the prospective International T cell Lymphoma Project, which described a 3-year PFS of 47% in ALK-negative patients with ALCL [ 7 , 8 ]. Comparing our findings to CHOP-treated patients in the ECHELON-2 trial, recognizing the caveat that 32% of such patients were of non-ALCL CD30+ PTCL subtypes, the outcomes of our cohort appeared inferior (3-year TTF 43.8% in our cohort vs 49% PFS in ECHELON-2).…”

“…Of note, the relapse rate in patients undergoing ASCT consolidation was 24.5% (95% CI 8.6–58.4), as compared to 22.2% (95% CI 13.7–34.7) in those potentially eligible (at least 65 years of age and in CR after induction) but who did not undergo ASCT. The International T cell Lymphoma Project recently reported similar low rates of ASCT (7%) in ALK-negative ALCL [ 8 ].…”

“…Retrospective studies support CHOEP in this context, the Nordic Lymphoma Group study reported improved survival outcomes (HR 0.48, 95% CI 0.32–0.74) when compared to CHOP in sALCL [ 9 , 17 ]. The T cell lymphoma project also reported a trend towards improved outcomes with etoposide regimens with superior 5-year OS (56% vs 69% for etoposide-containing regimens, p = 0.05) and a trend towards improved 5-year PFS (39% vs 50% for etoposide-containing regimens, p = 0.18) [ 8 ]. However, despite the potential benefit of CHOEP in sALCL, this regimen confers increased risk of morbidity and mortality compared to CHOP, particularly for patients above 60 years of age, as reported in the German NHL-B trial [ 18 ].…”

“…Cyclophosphamide, adriamycin, vincristine, prednisolone (CHOP) has been the standard of care for frontline sALCL for decades, delivering 5-year overall survival (OS) rates of 70-81% for ALK-positive cases [3][4][5] and 42-49% for ALKnegative cases [4][5][6]. The International T cell Project has reported results of 235 ALK-negative patients with sALCL, describing overall response rate (ORR) and complete response (CR) rates of 77% and 63% respectively, median progression free survival (PFS) of 41 months (95% CI 17-62) and 5-year OS rate of 49% (95% CI 35-59) [7,8]. The addition of etoposide to CHOP (CHOEP) has been suggested to be superior to CHOP in ALK-positive sALCL.…”

Role of lenalidomide in the treatment of peripheral T-cell non-Hodgkin lymphomas

“…Due to its rarity, the treatment approach has historically been similar to that used for aggressive B-cell neoplasms, such as diffuse large B-cell lymphoma (DLBCL)[ 3 , 4 ]. However, except for anaplastic lymphoma kinase (ALK)-positive anaplastic lymphoma (ALCL), treatment efficacy is limited compared to DLBCL, disease relapse is frequent even after high-dose therapy and autologous stem-cell transplantation, and long-term responses are seldom observed[ 1 , 5 - 8 ]. Allogeneic stem-cell transplantation often remains the only curative option, but many elderly and/or relapsed/refractory (R/R) patients are not eligible, and treatment morbidity and mortality are not negligible[ 9 ].…”