ALK negative

The patient's condition deteriorated, and she died during her hospitalization. This case reviews the clinicopathologic findings of pcALCL, emphasizes the importance of clinicopathologic correlation in differentiating between CD30+ lymphoproliferative disorders, highlights the extremely rare phenomenon of systemic intramuscular and visceral disseminated disease occurring in pcALCL, and discusses implications for prognosis.

Immunotherapy was received by 91.4% of patients, with Alectinib and Osimertinib being common. Limitations include the observational design, small sample size, and short follow-up period, impacting the generalizability and long-term outcome assessment. Future research should address these limitations and explore longitudinal outcomes and emerging therapies.

Differentiating anaplastic lymphoma kinase-negative anaplastic large cell lymphoma of the scalp from a ruptured epidermal cyst-like mass proved challenging. We recommend considering the possibility of anaplastic large cell lymphoma if an epidermal cyst-like mass does not respond to antibiotics or conventional dressing, as illustrated by our rare case.

ALK-positive patients were significantly younger than ALK-negative patients, and survival analyses showed that both ALK-positive and younger age (≤ 40 years) were favorable prognostic factors. This is the largest series of primary CNS ALCL reported to date, which demonstrates a high proportion of ALK-positive cases and favorable outcomes for both younger and ALK-positive patients despite the involvement of a sensitive anatomic site.

This case underscores the importance of early biopsy and molecular testing when standard treatments fail. Early recognition and routine examinations, including lymph node assessments and skin biopsies, are critical for improving patient outcomes, as timely diagnosis leads to more effective treatment options and potential remission.

Screening for ALK rearrangements with IHC is both reliable and cost effective. In-house testing with IHC removes reliance on send-out testing for ALK detection, effectively cutting costs and decreasing TAT. Additionally, the creation of a reflex algorithm can improve lung cancer biomarker testing processes within hospitals.

These findings provide novel insights into the molecular portrait of ALCL, that could help improve treatment strategies and the prognosis for ALCL patients.

P1/2, N=18, Completed, University of Colorado, Denver | Active, not recruiting --> Completed

Gene expression profiling data have shownthat ALK-negative ALCL has distinctive molecular signatures, different from ALK+ ALCL and other T-cell lymphomas. Better understanding of the morphologic, immunophenotypic, genetic and molecular features of ALK-negative ALCL will help establish the correct diagnosis, guide therapeutic strategies and improve patient outcomes.

NGS is not cost-effective for advanced EGFR/ALK-negative NSCLC, but has a survival benefit over sequential SGT. Our findings provide a basis for decision-making regarding the coverage and clinical utilization of NGS in regions where EGFR alterations are prevalent.

This multicenter registration study investigated tissue-based NGS for a specific patient population with NSCLC in Taiwan.

P1/2, N=22, Active, not recruiting, Laekna Limited | Recruiting --> Active, not recruiting | N=167 --> 22

P=N/A, N=44, Completed, Washington University School of Medicine | Active, not recruiting --> Completed | Trial completion date: Dec 2024 --> Nov 2023 | Trial primary completion date: Dec 2024 --> Nov 2023

This analysis of IMS using targeted sequencing data, highlighted some possibleassociations between intratumoral microorganisms and lymphoma-specific subtypes, especially in indolentsubtypes of ALCL (BIA- and pc-) compared to systemic ALCL. Further analyses with more cases andconfirmatory techniques might confirm these initial findings. Figure.

P1/2, N=28, Recruiting, Henan Cancer Hospital | Trial primary completion date: Feb 2024 --> Jun 2024

In advanced NSCLC, ICI treatment was linked to an elevated risk of pneumonitis across all grades (1-5) as well as high-grade occurrences (3-5) compared to chemotherapy. Notably, individuals with squamous histology and high PD-L1 expression, along with those lacking a history of prior treatment, demonstrated a heightened susceptibility to developing immune-related pneumonitis of all grades (1-5) and high grades (3-5). These observations provide valuable insights for clinicians seeking to enhance the management of pulmonary toxicity associated with immunotherapy.

We discuss the role of NGS as well as its potential benefit in patients with unresectable, ALK-negative metastatic disease. Considering this case and previous literature, we support the use of NGS for patients requiring systemic treatment.

Three cases previously classified as PTCL CD30+CD15+ showed DUSP22/IRF4 rearrangements, favouring a diagnosis of ALCL, ALK-. Our results suggest that cases previously designated PTCL CD30+CD15+, likely fall within the spectrum of ALCL, ALK-; additionally, a subset of ALCL, ALK- with DUSP22/IRF4 rearrangement expresses CD15, consistent with previous reports and expands the immunophenotypic spectrum of this lymphoma subgroup.

P2, N=148, Active, not recruiting, Daiichi Sankyo | Trial completion date: Sep 2025 --> Apr 2028

P2, N=30, Active, not recruiting, Northwestern University | Trial completion date: Aug 2023 --> Aug 2024

The histologic features of CSM present a unique set of challenges posing a diagnostic dilemma, as they can bear resemblance to a range of benign and malignant cutaneous neoplasms including ALK-negative epithelioid cell histiocytoma, epithelioid perineurioma, malignant or nevoid melanoma, and epithelioid sarcoma. An accurate diagnosis is crucial for guiding proper clinical management considering that this entity typically demonstrates an excellent prognosis following a complete surgical excision.

Symptoms of androgen deficiency should be tracked in male patients with ALK-positive ANSCLC who are receiving alectinib, and testosterone replacement should be considered, as appropriate.

P2, N=373, Completed, Novartis Pharmaceuticals | Active, not recruiting --> Completed

This study demonstrated that participating in clinical trials resulted in a survival benefit that reduced the risk of death by 29.6% compared to receiving SOC in EGFR-wild-type and ALK-negative lung adenocarcinoma.

While combination of these factors was highly predictive for ICIs, it was not associated with outcomes of chemotherapy treatment. Easily available characteristics of the patients allow for highly accurate predictions of outcomes of single-agent ICI therapy in chemotherapy-pretreated NSCLC.

P1, N=38, Terminated, CSPC ZhongQi Pharmaceutical Technology Co., Ltd. | N=63 --> 38 | Recruiting --> Terminated | Trial primary completion date: Mar 2022 --> Jun 2023; The sponsor has adjusted its R&D strategy.

P1/2, N=13, Active, not recruiting, City of Hope Medical Center | Trial primary completion date: Jun 2024 --> May 2023

P2, N=33, Recruiting, Great Novel Therapeutics Biotech & Medicals Corporation | Not yet recruiting --> Recruiting

P1/2, N=35, Active, not recruiting, Hackensack Meridian Health | Trial completion date: Feb 2024 --> May 2024 | Trial primary completion date: Feb 2024 --> May 2024

P2, N=48, Active, not recruiting, City of Hope Medical Center | Trial completion date: Dec 2023 --> Dec 2024

P1/2, N=13, Active, not recruiting, City of Hope Medical Center | Trial completion date: Dec 2023 --> Jun 2024 | Trial primary completion date: Dec 2023 --> Jun 2024

In conclusion, 44% of ALCL patients, regardless of histological subtypes, showed a loss of/decrease in CD30 expression after receiving BV-containing therapy, but this phenomenon was not observed in CHL patients. A higher cumulative dose of BV and a lower amount of CD30 antigen in tumor cells in the initial biopsy materials might be predictors of a loss of/decrease in CD30 expression in ALCL patients.

As a unique class of tumors that rarely metastasize, IMTs have an unknown etiology and pathogenesis, and distant metastasis is primarily observed in patients with negative activin receptor-like kinase (ALK) expression. The preferred treatment for IMT is complete surgical resection, and the effectiveness of adjuvant therapy for patients with distant metastases is still being determined. The clinical presentation of IMT lacks specificity and is often related to the location of tumor growth, which poses a diagnostic challenge. Pathological immunohistochemistry is the only way to confirm the diagnosis at present. Our case report reminds clinicians that a category of ALK-negative IMT with a tendency toward distant metastasis should not be ignored.

We showed that following first-line immunochemotherapy, chemo-free maintenance by ICIs plus anti-angiogenesis and on-demand chemo-rechallenge provided comparable efficacy to chemo-on maintenance in terms of PFS, thus allowing the minimization of cytotoxic drugs without compromising therapeutic effectiveness. In addition, anti-angiogenesis is essential during chemo-free maintenance.

No abstract available

We subsequently stained whole tissue sections of these three cases with the ALK01 antibody and found that these three cases were indeed positive with the ALK01 protocol, suggesting that the absence of staining on the tissue microarray samples was due to a combination of sampling error as well as a dimmer signal with the ALK01 protocol. Our study demonstrates that our 5A4-based protocol is non-inferior to the ALK01 antibody for the diagnosis of ALK-positive anaplastic large cell lymphoma, thus allowing our laboratory to discontinue the use of the ALK01-based protocol.

P1/2, N=40, Suspended, Myeloid Therapeutics

P2, N=36, Not yet recruiting, Second Affiliated Hospital of Nanchang University

P1, N=18, Active, not recruiting, UNC Lineberger Comprehensive Cancer Center

P2, N=110, Recruiting, Sichuan Kelun Pharmaceutical Research Institute Co., Ltd. | Not yet recruiting --> Recruiting | Trial completion date: Apr 2025 --> Apr 2026 | Trial primary completion date: Aug 2023 --> Aug 2024

Furthermore, in a subset of patients with initial site of progression at a non-primary-site, patients undergoing concurrent immunotherapy had longer PFS than those undergoing consolidative immunotherapy (median 22.7 vs. 11.9 months; P=0.03). Concurrent immunotherapy with chemoradiotherapy may be associated with improved disease progression outcomes as compared to consolidative immunotherapy following chemoradiotherapy.

P1/2, N=28, Recruiting, Henan Cancer Hospital | Not yet recruiting --> Recruiting