AI Drug Discovery for Pharma and Biotech

Drug discovery

1

drug

With orphan designation

Overview

Primary cutaneous lymphoma (PCL) encompasses rare, heterogeneous non-Hodgkin lymphomas arising in the skin without extracutaneous involvement at diagnosis. Major subtypes include cutaneous T-cell lymphoma (CTCL) (e.g., mycosis fungoides, Sézary syndrome) and cutaneous B-cell lymphoma (CBCL) (e.g., primary cutaneous follicle center, marginal zone, and diffuse large B-cell lymphoma, leg type). Prognosis varies widely, with indolent forms demonstrating high survival rates (e.g., 10-year survival >90% for some CBCL subtypes) and aggressive subtypes (e.g., diffuse large B-cell lymphoma, leg type) showing 5-year survival rates of ~50% [1][4][7][11].

Population

  • Incidence: CTCL accounts for 71% of cases (7.7/million person-years), CBCL 29% (3.1/million) [2][14].

  • Demographics: Higher incidence in males (male-female ratio 1.7:1) [2], non-Hispanic Blacks (CTCL: 10.0/million) and non-Hispanic whites (CBCL: 3.5/million) [2][5][14]. Median age at diagnosis: 50–70 years [5][9].

Burden

  • Mortality: 5-year survival exceeds 95% for indolent subtypes but drops to 50–60% for aggressive forms [1][4][11]. Sézary syndrome carries a median survival of ≤4 years [9].

  • Relapse: Common in CBCL (56% relapse post-R-CHOP) [7] and CTCL, necessitating lifelong monitoring [4][11].

  • Quality of life: Chronic pruritus, disfigurement, and treatment-related complications (e.g., skin infections, therapy resistance) contribute to morbidity [1][5][12].

Therapies

  • Skin-directed therapies: First-line for localized disease—topical corticosteroids, phototherapy (UVB/PUVA), radiation (total skin electron beam for extensive CTCL) [3][7][11].

  • Systemic therapies: Retinoids, monoclonal antibodies (e.g., rituximab for CBCL), interferon-α, and combination regimens (e.g., R-CHOP for aggressive CBCL) [4][7][11].

  • Novel agents: Emerging use of checkpoint inhibitors, Bruton tyrosine kinase inhibitors, and CAR T-cell therapy for refractory cases [7][8].

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

Research Papers

997 drug discovery papers related to Primary cutaneous lymphoma, with 4 first-in-class and 12 next-in-class early-stage therapies forecasted to outperform the average preclinical success rate. Recent publications:

997 drug discovery papers related to Primary cutaneous lymphoma, with 4 first-in-class and 12 next-in-class early-stage therapies forecasted to outperform the average preclinical success rate. Recent publications:

2026-06-11 | Case Report: Cutaneous niche-restricted malignant phenotypes in PTCL-NOS revealed by single-cell sequencing.

Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) presenting with disseminated cutaneous involvement represents an aggressive disease subset with poor response to conventional chemotherapy and dismal prognosis. The tissue-specific molecular mechanisms driving cutaneous aggression remain poorly characterized at single-cell resolution. Here we report a 67-year-old male PTCL-NOS patient with hypertension and coronary artery disease history, presenting with generalized cutaneous nodules and rapid progression despite multi-line chemotherapy. Single-cell RNA sequencing (scRNA-seq) performed on paired skin lesions and peripheral blood at diagnosis revealed striking microenvironmental dichotomy: skin-resident malignant T cells exhibited hyperproliferative phenotypes (high CDC20B, HIST1H3B, MKI67+), activation of NF-κB and IL-17 signaling, and extensive crosstalk with endothelial cells; conversely, blood-derived lymphoma cells displayed immune evasion signatures and metabolic stress markers. Copy number variation analysis confirmed clonal expansion across both compartments with distinct tissue-specific transcriptional programs. Despite CHOP, CHOEP, DA-EPOCH, and AC-CHOP (azacitidine plus chidamide) regimens, the patient experienced primary refractory disease and died 6 months from diagnosis following COVID-19 superinfection. To our knowledge, this is the first case reporting single-cell transcriptomic comparison of skin versus blood compartments in PTCL-NOS, revealing how cutaneous microenvironment sculpts aggressive malignant phenotypes and providing potential targets for compartment-specific therapy.

Open article ↗



2026-06-01 | Primary cutaneous diffuse large B-cell lymphoma, leg type: A case with atypical immunophenotype and favorable response to R-CHOP

Primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT), is a rare and aggressive neoplasm in which early diagnosis is critical for prognostic optimization. We report the case of a 73-year-old man presenting with multiple erythematous-violaceous tumors on both legs. Histopathology revealed a diffuse proliferation of large B cells with a Ki-67 index of >90% and an atypical immunophenotype: CD10+, CD5+, and BCL2-. Despite coexpression of CD79a—classically associated with more aggressive behavior—the patient showed a favorable clinical response to R-CHOP, achieving near-complete regression after the third cycle. This case underscores the biological heterogeneity of PCDLBCL-LT and raises the possibility of unrecognized prognostic modifiers influencing treatment outcomes. Further studies are needed to elucidate the molecular determinants underlying clinical variability and to improve risk stratification and therapeutic decision-making in this lymphoma subtype.

Open article ↗



2026-06-01 | LY16 Primary cutaneous follicle centre lymphoma arising at a COVID-19 vaccination site with spontaneous regression

Abstract Primary cutaneous follicle centre lymphoma (PCFCL) is an indolent cutaneous B-cell lymphoma that may rarely show spontaneous regression. The impact of immune stimulation, including vaccination, on the behaviour and morphology of cutaneous lymphomas remains poorly understood. We present a case of a 73-year-old man who presented with an > 30-year history of an asymptomatic truncal eruption consisting of erythematous patches and indurated plaques. He developed an erythematous raised lesion over the right deltoid directly following COVID-19 vaccination to this area, which progressively enlarged into two tumoral nodules measuring 5–6 cm. Skin biopsies from the right arm and trunk demonstrated a diffuse dermal B-cell infiltrate (CD20+, PAX5+) coexpressing CD10 and BCL6, with variable BCL2 positivity and a high proliferative index (Ki-67 ∼80%). Molecular genetic analysis confirmed a monoclonal B-cell population with concordant immunoglobulin gene rearrangements across multiple biopsy sites, supporting a diagnosis of the diffuse variant of PCFCL. Full staging with positron emission tomography–­computed tomography demonstrated fluorodeoxyglucose avidity confined to the right deltoid lesions, with no systemic disease and a clear bone marrow. Notably, the deltoid tumours involuted spontaneously prior to any treatment, while the indurated truncal lesions progressed. Repeat biopsies demonstrated persistent clonal B-cell infiltrates, with admixed CD4-predominant T cells raising clinicopathological concern for mycosis fungoides. However, T-cell clonality was not diagnostic. The patient received rituximab monotherapy with near-complete clearance. This case is notable for tumoral PCFCL with high-grade appearance arising at a COVID-19 vaccination site with spontaneous regression, supporting a potential antigen-driven immunological trigger. Vaccine-associated triggering or apparent transformation of PCFCL represents an unanswered aspect of dermatological oncology and may influence future diagnostic and management approaches.

Open article ↗



2026-06-11 | Case Report: Cutaneous niche-restricted malignant phenotypes in PTCL-NOS revealed by single-cell sequencing.

Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) presenting with disseminated cutaneous involvement represents an aggressive disease subset with poor response to conventional chemotherapy and dismal prognosis. The tissue-specific molecular mechanisms driving cutaneous aggression remain poorly characterized at single-cell resolution. Here we report a 67-year-old male PTCL-NOS patient with hypertension and coronary artery disease history, presenting with generalized cutaneous nodules and rapid progression despite multi-line chemotherapy. Single-cell RNA sequencing (scRNA-seq) performed on paired skin lesions and peripheral blood at diagnosis revealed striking microenvironmental dichotomy: skin-resident malignant T cells exhibited hyperproliferative phenotypes (high CDC20B, HIST1H3B, MKI67+), activation of NF-κB and IL-17 signaling, and extensive crosstalk with endothelial cells; conversely, blood-derived lymphoma cells displayed immune evasion signatures and metabolic stress markers. Copy number variation analysis confirmed clonal expansion across both compartments with distinct tissue-specific transcriptional programs. Despite CHOP, CHOEP, DA-EPOCH, and AC-CHOP (azacitidine plus chidamide) regimens, the patient experienced primary refractory disease and died 6 months from diagnosis following COVID-19 superinfection. To our knowledge, this is the first case reporting single-cell transcriptomic comparison of skin versus blood compartments in PTCL-NOS, revealing how cutaneous microenvironment sculpts aggressive malignant phenotypes and providing potential targets for compartment-specific therapy.

Open article ↗



2026-06-01 | Primary cutaneous diffuse large B-cell lymphoma, leg type: A case with atypical immunophenotype and favorable response to R-CHOP

Primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT), is a rare and aggressive neoplasm in which early diagnosis is critical for prognostic optimization. We report the case of a 73-year-old man presenting with multiple erythematous-violaceous tumors on both legs. Histopathology revealed a diffuse proliferation of large B cells with a Ki-67 index of >90% and an atypical immunophenotype: CD10+, CD5+, and BCL2-. Despite coexpression of CD79a—classically associated with more aggressive behavior—the patient showed a favorable clinical response to R-CHOP, achieving near-complete regression after the third cycle. This case underscores the biological heterogeneity of PCDLBCL-LT and raises the possibility of unrecognized prognostic modifiers influencing treatment outcomes. Further studies are needed to elucidate the molecular determinants underlying clinical variability and to improve risk stratification and therapeutic decision-making in this lymphoma subtype.

Open article ↗



2026-06-01 | LY16 Primary cutaneous follicle centre lymphoma arising at a COVID-19 vaccination site with spontaneous regression

Abstract Primary cutaneous follicle centre lymphoma (PCFCL) is an indolent cutaneous B-cell lymphoma that may rarely show spontaneous regression. The impact of immune stimulation, including vaccination, on the behaviour and morphology of cutaneous lymphomas remains poorly understood. We present a case of a 73-year-old man who presented with an > 30-year history of an asymptomatic truncal eruption consisting of erythematous patches and indurated plaques. He developed an erythematous raised lesion over the right deltoid directly following COVID-19 vaccination to this area, which progressively enlarged into two tumoral nodules measuring 5–6 cm. Skin biopsies from the right arm and trunk demonstrated a diffuse dermal B-cell infiltrate (CD20+, PAX5+) coexpressing CD10 and BCL6, with variable BCL2 positivity and a high proliferative index (Ki-67 ∼80%). Molecular genetic analysis confirmed a monoclonal B-cell population with concordant immunoglobulin gene rearrangements across multiple biopsy sites, supporting a diagnosis of the diffuse variant of PCFCL. Full staging with positron emission tomography–­computed tomography demonstrated fluorodeoxyglucose avidity confined to the right deltoid lesions, with no systemic disease and a clear bone marrow. Notably, the deltoid tumours involuted spontaneously prior to any treatment, while the indurated truncal lesions progressed. Repeat biopsies demonstrated persistent clonal B-cell infiltrates, with admixed CD4-predominant T cells raising clinicopathological concern for mycosis fungoides. However, T-cell clonality was not diagnostic. The patient received rituximab monotherapy with near-complete clearance. This case is notable for tumoral PCFCL with high-grade appearance arising at a COVID-19 vaccination site with spontaneous regression, supporting a potential antigen-driven immunological trigger. Vaccine-associated triggering or apparent transformation of PCFCL represents an unanswered aspect of dermatological oncology and may influence future diagnostic and management approaches.

Open article ↗



Access all drug discovery articles and probability of success in trials forecasts:

Access all drug discovery articles and probability of success in trials forecasts:

Drug Discovery Landscape

1 orphan drug designation for Primary cutaneous lymphoma.

1 orphan drug designation for Primary cutaneous lymphoma.

Drug

Therapy type

Regulator

Orphan designation

Approval

Sponsor

miltefosine

small molecules

FDA

2009-03-18

ExperGen Drug Development GmbH

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228 Park Ave S,
New York, USA.

At Explority, we build first-of-its-kind AI to bring clarity to the earliest and riskiest stages of pharmaceutical research by forecasting which therapies are most likely to succeed. Explority AI web and mobile applications are properties of the Explority AI Inc., a company registered in the United States (File No. 10320493).
For all questions: support@explority.ai

Copyright © 2026 Explority AI Inc.

Explority AI logo

228 Park Ave S,
New York, USA.

At Explority, we build first-of-its-kind AI to bring clarity to the earliest and riskiest stages of pharmaceutical research by forecasting which therapies are most likely to succeed. Explority AI web and mobile applications are properties of the Explority AI Inc., a company registered in the United States (File No. 10320493).
For all questions: support@explority.ai

Copyright © 2026 Explority AI Inc.

Explority AI logo

228 Park Ave S,
New York, USA.

At Explority, we build first-of-its-kind AI to bring clarity to the earliest and riskiest stages of pharmaceutical research by forecasting which therapies are most likely to succeed. Explority AI web and mobile applications are properties of the Explority AI Inc., a company registered in the United States (File No. 10320493).
For all questions: support@explority.ai

Copyright © 2026 Explority AI Inc.