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

Andrei Shustov, Maria Elena Cabrera, Monica Civallero, Monica Bellei, Young Hyeh Ko, Martina Manni, Tetiana Skrypets, Steven M Horwitz, Carmino Antonio De Souza, John A Radford, Sabela Bobillo, Maria Virginia Prates, Andrés J M Ferreri, Carlos Chiattone, Michele Spina, Julie M Vose, Annalisa Chiappella, Daniele Laszlo, Dario Marino, Caterina Stelitano, Massimo Federico, Andrei Shustov, Maria Elena Cabrera, Monica Civallero, Monica Bellei, Young Hyeh Ko, Martina Manni, Tetiana Skrypets, Steven M Horwitz, Carmino Antonio De Souza, John A Radford, Sabela Bobillo, Maria Virginia Prates, Andrés J M Ferreri, Carlos Chiattone, Michele Spina, Julie M Vose, Annalisa Chiappella, Daniele Laszlo, Dario Marino, Caterina Stelitano, Massimo Federico

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.

Conflict of interest statement

Conflict-of-interest disclosure: S.M.H. has consulted, received honorarium from, or participated in advisory boards for ADC Therapeutics, C4 Therapeutics, Celgene, Janssen, Kura Oncology, Kyowa Hakko Kirin, Myeloid Therapeutics, Seattle Genetics, Takeda, Trillium Therapeutics, Verastem, and Vividion Therapeutics; and received research support for clinical trials from ADC Therapeutics, Affimed, Aileron, Celgene, Daiichi Sankyo, Forty Seven, Inc., Kyowa Hakko Kirin, Millennium/Takeda, Portola Pharmaceuticals, Seattle Genetics, Trillium Therapeutics, and Verastem. The remaining authors declare no competing financial interests.

© 2021 by The American Society of Hematology.

Figures

Graphical abstract
Graphical abstract
Figure 1.
Figure 1.
OS and PFS. Kaplan-Meier analysis of OS and PFS in ALK– ALCL patients. (A) Five-year rate of OS was 49% (95% CI, 35-59). (B) Five-year rate of PFS was 43% (95% CI, 20-69).
Figure 2.
Figure 2.
OS and PFS according to anthracycline (Anthra) and Anthra + etoposide (ETO) treatments. Kaplan-Meier analysis of OS and PFS in patients with ALK– ALCL stratified according to use of ETO in combination with Anthra. (A) Five-year rates of OS in the ETO cohort vs no ETO cohort were 69% vs 44%, respectively. (B) Five-year rates of PFS in the ETO cohort vs the no ETO cohort were 50% vs 39%, respectively.
Figure 3.
Figure 3.
OS and PFS according to IPI and PIT. Kaplan-Meier analysis of OS (A) and PFS (C) stratified according to IPI-defined risk groups. Kaplan-Meier analysis of OS (B) and PFS (D) stratified according to PIT-defined risk groups.

Source: PubMed

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