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RARE DISEASE

Anaplastic large cell lymphoma

Synonyms: ALCL, CD30 positive anaplastic large cell lymphoma, Ki-1 positive anaplastic large cell lymphoma, Primary systemic ALCL, sACL

Drug discovery

drugs

With orphan designations

Overview

Anaplastic large cell lymphoma (ALCL) is a rare CD30-positive T-cell non-Hodgkin lymphoma with distinct subtypes: systemic (ALK-positive or ALK-negative), primary cutaneous, and breast implant-associated (BIA-ALCL). ALK-positive cases, more common in children/young adults, have favorable prognoses with anthracycline-based chemotherapy (e.g., CHOP/CHOEP). ALK-negative disease, prevalent in older adults, has poorer outcomes. Brentuximab vedotin (anti-CD30) and stem cell transplantation are key for relapsed/refractory cases. BIA-ALCL is linked to textured implants and typically resolves with implant/capsule removal [1][6][7][12][18].

Population

Represents 2-3% of all non-Hodgkin lymphomas (~15% of T-cell lymphomas) [1][4][7].
ALK-positive: Median age 34, 10-20% of childhood lymphomas [7][12].
ALK-negative: Median age 58, 1-9 cases/100,000; male predominance [7][19].

Burden

Survival: 5-year OS 70-80% (ALK-positive) vs. 33-49% (ALK-negative) [7][12].
Complications: 30-40% relapse in systemic ALCL; BIA-ALCL incidence 1:30,000 with textured implants [4][18][19].
Mortality: Aggressive ALK-negative subtypes account for most ALCL-related deaths [7][8][12].

Therapies

First-line: CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) ± etoposide (CHOEP) for ALK-positive [1][8][12].
Targeted therapy: Brentuximab vedotin (CD30-directed) for relapsed/refractory or frontline ALK-negative cases [1][12][14].
Advanced disease: Stem cell transplantation (autologous/allogeneic); BIA-ALCL requires implant removal with capsulectomy [3][8][18].

Categories: rare hematological diseases, rare neoplastic diseases, rare transplant-related disorders

Research Papers

1,411 drug discovery papers related to Anaplastic large cell lymphoma, with 3 first-in-class and 7 next-in-class early-stage therapies forecasted to outperform the average preclinical success rate. Recent publications:

2026-06-27 | CircZBTB46, a promising therapeutic target in crizotinib resistant ALK-positive T lymphomas.

Circular RNAs (circRNAs) are increasingly recognized as functional non-coding transcripts with oncogenic potential. Here, a comprehensive analysis of circRNA expression in primary ALK(+) anaplastic large-cell lymphoma (ALK( + ) ALCL) is presented. Integrated transcriptomic profiling revealed that aberrant expression of circZBTB46 and of its linear host transcript, normally restricted to dendritic cells, is exclusive to ALK(+) lymphoma cells and driven by the oncogenic NPM1::ALK/STAT3 axis. Functional studies showed that circZBTB46, unlike its protein-coding counterpart, promotes resistance to the ALK inhibitor crizotinib. Silencing circZBTB46 restored crizotinib sensitivity in resistant ALCL cells both in vitro and in vivo. Transcriptomic analyses identified PIP5K1C as a downstream effector regulated through a competitive endogenous RNA mechanism in which circZBTB46 acts as a sponge to miR-25-3p, alleviating its repression of PIP5K1C. These findings uncover a previously unrecognized mechanism of drug resistance in ALK( + ) ALCL and establish circZBTB46 as a promising therapeutic target.

Open article ↗

2026-06-25 | [A patient with dizziness and gait instability - a diagnostic challenge].

A 58-year-old patient presented with progressive cerebellar ataxia and lymphocytic pleocytosis with normal MRI findings. Detection of Anti-TR(DNER) antibodies led to the diagnosis of paraneoplastic encephalitis. Tumor workup revealed anaplastic large cell lymphoma. Combined immunotherapy and chemotherapy resulted in clinical stabilization.

Open article ↗

2026-06-05 | CircRNAs derived from the tyrosine phosphatase PTPN22 impact chemosensitivity in ALK-positive T-cell lymphomas.

Anaplastic large cell lymphoma (ALCL) is a subtype of T-cell non-Hodgkin lymphoma (NHL), classified into ALK(+) and ALK(-) subtypes, based on translocations of the ALK gene. ALK(+) ALCL have a favorable prognosis with polychemotherapy, yet some patients develop early chemoresistance, leading to treatment failure. The molecular mechanisms underlying this resistance remain poorly defined. Circular RNAs (circRNAs) have recently emerged as regulators of drug resistance in cancer, but their role in T-NHLs is largely unexplored. A comprehensive analysis of circRNA expression was performed here in primary ALK(+) ALCL biopsies. RNA-Seq identified 12 circRNAs associated with early relapse, including isoforms from the PTPN22 gene (circPTPN22), significantly upregulated in relapsed patients. Functional analyses showed that the ALK/STAT3 signaling pathway regulates circPTPN22 expression, linking oncogenic signaling to circRNA regulation. It was also found that circPTPN22 isoforms modulate responses to chemotherapy by regulating the arginine methyltransferase CARM1, a key enzyme involved in transcriptional regulation. Loss of CARM1 expression promoted drug tolerance in chemosensitive ALK(+) lymphoma cells. These findings identify the circPTPN22/CARM1 axis as a regulator of chemosensitivity and propose CARM1 inhibition as a potential strategy to overcome chemoresistance in patients with ALK(+) ALCL.

Open article ↗

2026-06-27 | CircZBTB46, a promising therapeutic target in crizotinib resistant ALK-positive T lymphomas.

Open article ↗

2026-06-25 | [A patient with dizziness and gait instability - a diagnostic challenge].

Open article ↗

2026-06-05 | CircRNAs derived from the tyrosine phosphatase PTPN22 impact chemosensitivity in ALK-positive T-cell lymphomas.

Open article ↗

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Drug Discovery Landscape

8 orphan drug designations for Anaplastic large cell lymphoma, including 2 approved therapies.

Drug	Therapy type	Regulator	Orphan designation	Approval	Sponsor
CD30-Targeted Genetically-modified Autologous T-cell immunotherapy	cell therapies	FDA	2024-01-29	—	Wu Han Bio-raid Biotech Co., Ltd.
Belinostat	small molecules	EMA	2012-10-10	—	Onxeo DK, Filial af Onxeo S.A., Frankrig
crizotinib [Xalkori]	small molecules	FDA	2012-09-28	2021-01-14	Pfizer, Inc.
Mogamulizumab	antibodies	EMA	2012-01-11	—	Kyowa Kirin Holdings B.V.
mogamulizumab	antibodies	FDA	2010-11-02	—	Kyowa Kirin Pharmaceutical Development, Inc.
Darinaparsin	small molecules	FDA	2010-09-13	—	Solasia Pharma K.K.
Brentuximab vedotin [Adcetris]	antibodies	EMA	2009-01-15	—	Takeda Pharma A/S
brentuximab vedotin [Adcetris]	antibodies	FDA	2008-10-23	2011-08-19	Seagen Inc.

Anaplastic large cell lymphoma

Anaplastic large cell lymphoma

Anaplastic large cell lymphoma

Overview

Population

Burden

Therapies

Categories: rare hematological diseases, rare neoplastic diseases, rare transplant-related disorders

Research Papers

2026-06-27 | CircZBTB46, a promising therapeutic target in crizotinib resistant ALK-positive T lymphomas.

2026-06-25 | [A patient with dizziness and gait instability - a diagnostic challenge].

2026-06-05 | CircRNAs derived from the tyrosine phosphatase PTPN22 impact chemosensitivity in ALK-positive T-cell lymphomas.

2026-06-27 | CircZBTB46, a promising therapeutic target in crizotinib resistant ALK-positive T lymphomas.

2026-06-25 | [A patient with dizziness and gait instability - a diagnostic challenge].

2026-06-05 | CircRNAs derived from the tyrosine phosphatase PTPN22 impact chemosensitivity in ALK-positive T-cell lymphomas.

Drug Discovery Landscape

Updated: Aug 14, 2026