Anaplastic Large Cell Lymphoma, Alk‐negative: Analysis of 235 Cases Collected by the T‐cell Project

Abstract

Introduction: Anaplastic Large Cell Lymphoma, ALK-Negative(ALCL, ALK-) is an aggressive lymphoid neoplasm of T/null-cell lineage with strong expression of CD30, which represent 5.5% of all PTCL and NKTCL, with a unique ethnic and geographical distribution. ALCL, ALK-displays a poorer outcome compared to ALK-positive, with a 5-year OS of 49% and 70%, respectively. This study aims to provide accurate and update information on prognostic factors, therapy, and outcomes of ALK-ALCL registered in the T-Cell Project.Methods: Eligible patients (pts) with the first diagnosis of aggressive, mature PTCLs were prospectively registered at a dedicated website and baseline demographic, clinical and laboratory data, as well as therapy details and outcome data were collected. Results: From Sept 2006 to Feb 2018, a diagnosis of ALCL, ALK-was reported in 235 cases out of 1553 validated cases registered by 77 sites from 14 countries worldwide. The median age at diagnosis was 54 (range, 18-89) years with male predominance (61%). Stage III-IV disease was identified in 71% pts, bulky and bone marrow involvement were uncommon. Therapy was administered according to treating physician's standard practice. Out of 205 patients for which we have available data about treatment, in 9% were addressed to consolidating post-transplant chemotherapy.The overall response rate was 77% with 57% of patients achieving complete remission. After a median follow-up of 55 (95% CI, 36-75) months, the PFS was 41 (95% CI, 17-62) months, the 3-year and 5-year PFS rates were 47% and 39%, respectively. The median OS was 55 (95% CI, 36-75) months, 3-year and 5-year OS rates were 60% (95CI 48-72) and 49% (95CI35-59), respectively. International Prognostic Index (IPI) and the Prognostic Index for T-cell Lymphomas (PIT) were both predictive of clinical outcomes. Treatment with anthracycline and etoposide vs. anthracycline-only containing regimens was associated with a better OS( 3 and 5-year OS 56% and 44% vs 76% and 69%, respectively, (P = 0.05), but not PFS 3 and 5 year PFS 47% (95CI 32-59) and 39 % (95CI 29-48) vs. 65% (95CI 32-87) and 50% (95CI 36-89) respectively (P = 0.186).In the multivariate analysis the presence of B symptoms (P = 0.008), elevated LDH rate (P = 0.001), ECOG-PS >2 (P = 0.001) andPTL<150x10 9 (P = 0.05), were significant for OS. The presence of B symptoms (p = 0.02), elevated LDH (P = 0.001) and ECOG-PS>2 (P = 0.001) maintained their adverse prognostic value for PFS.Conclusions: ALCL, ALK-remains a difficult T cell lymphoma to be cured. Combinations regimens that include both etoposide and anthracycline might improve outcomes. In this large prospective ABSTRACT 283 cohort study, we observed an outcome comparable with a previous report from the retrospective International Lymphoma Project. The study underscores the urgent need for designing new treatment platforms for ALCL, ALK-, and establishes a benchmark for future prospective clinical trials.Background: Mycosis fungoides (MF) is a rare, generally indolent non-Hodgkin T-cell lymphoma of ...

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).…”

“…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.…”