DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for Hodgkins lymphoma — screening already-approved drugs against its 44-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleHodgkins lymphoma maps to a 44-gene Open Targets module — the target space DeCure's AI scientist screens approved drugs against.
DeCure.ai methodSignature reversal (LINCS) plus network proximity (STRING) rank already-approved drugs likely to perturb this module — the same engine that produces DeCure.ai's repurposing hypotheses.
Repurposing thesisScreening approved medicines against this disease module, then publishing the evidence for the strongest candidate. Known pharmacology and human exposure data make the first question sharper — they do not establish safety or efficacy in a new indication.
Research record
01
ResearchComing soon
Candidate research + dossier — target rationale, drug-repurposing thesis and evidence pack.proof: Published dossier + on-chain hash
02
ValidationComing soon
In-vitro biological validation at a contract research org (CRO).proof: CRO contract + in-vitro report
03
Peer review & paperComing soon
Peer-reviewed paper published open-access (preprint + journal).proof: DOI + open-access link + on-chain hash
Current lead
No approved-drug candidate for hodgkins lymphoma is corroborated in the literature DeepSearch retrieved. Some conditions are managed with non-pharmacological care — a device, surgery or physical therapy — rather than a medicine; that may be the case here, or the literature we found may simply be too sparse yet to support a drug-repurposing angle.
Molecular view
IL2 inducible T cell kinase (ITK) — ITK is one of the genes genetically linked to this disease in Open Targets — shown as context, not as a drug target we're pursuing: no approved-drug candidate for this disease is yet corroborated in the literature we found.
Loading structure…
helix sheet 3rdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 4HCU · 1.43 Å · ligand 3-{4-amino-1-[(3R)-1-propanoylpiperidin-3-yl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-N-[4-(propan-2-yl)phenyl]benzamide (13L). Experimental structure, not a prediction.
What the evidence adds up to
In the KEYNOTE-087 phase 2 study of pembrolizumab in 210 patients with relapsed or refractory classic Hodgkin lymphoma, the objective response rate was 71.9% (95% CI, 65.3-77.9), with a complete response rate of 27.6% and a partial response rate of 44.3% at a median follow-up of 27.6 months. Median duration of response was 16.5 months across all patients, ranging from 11.1 months in cohort 2 (patients ineligible for stem cell transplant due to chemorefractory disease) to 24.4 months in cohort 3 (progression after transplant without prior brentuximab vedotin). Median progression-free survival was not reached in patients who achieved complete response, but was 13.8 months for those with partial response and 10.9 months for stable disease. Treatment-related adverse events of any grade occurred in 72.9% of patients, with grades 3 and 4 in 12.0%; none were fatal.
A retrospective Russian study of 101 patients with relapsed/refractory classical Hodgkin lymphoma treated with nivolumab reported a response rate of 64%: 31.6% complete and 32.7% partial. At a median follow-up of 25 months, 2-year overall survival was 96% and median progression-free survival was 17.9 months. Adverse events of any grade occurred in 87.1% of patients, with severe (grade III–IV) events in 18.8%. A separate case series of three patients treated with nivolumab after allogeneic stem cell transplant reported objective responses in all three, but one patient developed immune-related polyarthritis requiring corticosteroids and methotrexate, leading to discontinuation.
Brentuximab vedotin, an anti-CD30 antibody-drug conjugate, was evaluated in a small Chilean retrospective study of 7 patients with relapsed or refractory Hodgkin lymphoma who had received a median of 4 prior treatment lines. Three of 6 evaluable patients achieved complete remission and proceeded to autologous stem cell transplant. The review of brentuximab vedotin safety notes that peripheral neuropathy and neutropenia are the most common side effects, and that combining it with bleomycin is contraindicated due to pulmonary toxicity. A 2009 study of prednimustine in 37 patients with non-Hodgkin lymphomas reported 22 complete and 10 partial remissions, but all partial responders and five complete responders relapsed during follow-up; this study is not specific to Hodgkin lymphoma and prednimustine is not mentioned in any of the other abstracts.
What is still missing: prospective randomised comparisons of PD-1 inhibitors against each other or against brentuximab vedotin in the relapsed/refractory setting; data on optimal sequencing of these agents; and trials that stratify patients by prior transplant status, chemorefractory status, or CD30 expression level to identify who benefits most from each drug.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Blood · 2019 · 330 citations · open access
Pembrolizumab in relapsed or refractory Hodgkin lymphoma: 2-year follow-up of KEYNOTE-087
AbstractProgrammed death-1 inhibitors are approved for patients with relapsed or refractory classic Hodgkin lymphoma (RRcHL). We present the 2-year follow-up of the phase 2 KEYNOTE-087 study of pembrolizumab in 210 patients, based on HL progression after autologous stem cell transplantation (ASCT) and subsequent brentuximab vedotin (BV; cohort 1); salvage chemotherapy and BV, with ineligibility for SCT owing to chemorefractory disease (cohort 2); and progression after SCT without BV (cohort 3). With a median follow-up of 27.6 months, the objective response rate (ORR) by blinded independent central review was 71.9% (95% CI, 65.3-77.9), the complete response rate (CRR) was 27.6%, and the partial response (PR) rate was 44.3%. Median duration of response was 16.5 months (range, 0.0+ to 27.0+ [+, no progressive disease at last assessment]) in all patients, 22.1 months in cohort 1, 11.1 months in cohort 2, and 24.4 months in cohort 3. Median progression-free survival was not reached in all patients with CR: 13.8 months (95% CI, 12.0-22.1) for patients with PR and 10.9 months (95% CI, 5.6-11.1) for patients with stable disease. Median overall survival was not reached in all patients or in any cohort. Treatment-related adverse events (TRAEs) of any grade occurred in 153 (72.9%) patients; grades 3 and 4 occurred in 25 (12.0%) patients; none resulted in death. Results confirmed effective antitumor activity, durability of response, and manageable safety of pembrolizumab monotherapy in RRcHL, regardless of prior treatment and including chemoresistant cHL. This trial was registered at www.clinicaltrials.gov as #NCT02453594.
Expert Opinion on Drug Safety · 2016 · 32 citations
A safety evaluation of brentuximab vedotin for the treatment of Hodgkin lymphoma
AbstractINTRODUCTION: Brentuximab vedotin is an anti-CD30 monoclonal antibody-drug conjugate approved for treating relapsed or refractory Hodgkin lymphoma. The pivotal trial demonstrated brentuximab vedotin's efficacy and manageable toxicity profile with peripheral neuropathy and neutropenia being the most common side effects. The phase I study of brentuximab vedotin combined with ABVD or AVD revealed its contraindication with bleomycin due to pulmonary toxicity. As trials continue to investigate the drug in frontline and relapsed settings, emerging safety data will further define brentuximab vedotin's role in managing Hodgkin lymphoma. AREAS COVERED: This article reviews the current literature on brentuximab vedotin in Hodgkin lymphoma treatment, both as a single agent and in combination regimens. The review focuses on safety findings from clinical trials, expected adverse events, and rare serious toxicities. EXPERT OPINION: Brentuximab vedotin is a breakthrough antibody-drug conjugate that may provide new options in earlier lines of therapy for Hodgkin lymphoma. Results from the ongoing phase III trial comparing ABVD to AVD + brentuximab vedotin will inform whether brentuximab vedotin adds benefit to frontline therapy over the current standard of care. The optimal duration of treatment and brentuximab vedotin's potential as an alternative to radiation in early stage disease still warrant investigation.
Journal for ImmunoTherapy of Cancer · 2017 · 32 citations · open access
PD-1 blockade induces remissions in relapsed classical Hodgkin lymphoma following allogeneic hematopoietic stem cell transplantation
AbstractBACKGROUND: Allogeneic hematopoietic stem cell transplantation and checkpoint blockade therapy are immune-based therapies that have activity in selected refractory hematologic malignancies. Interest has developed in combining these treatments for high-risk hematologic diseases. However, there is concern that checkpoint blockade could augment graft-versus-host disease, and very few studies have evaluated the safety of checkpoint blockade in the post-allogeneic setting. Here, we report the outcomes of three patients with relapsed classical Hodgkin's lymphoma following allogeneic transplant that were treated with the anti-PD-1 antibody, nivolumab. CASE PRESENTATIONS: Three patients with Hodgkin's lymphoma relapsed following allogeneic transplant received nivolumab therapy at our institution. All patients were free of graft-versus-host disease and were off of all systemic immunosuppressive medications at the time of nivolumab treatment. Nivolumab was well-tolerated in two of the patients. However, nivolumab had to be discontinued in one patient due to development of immune-related polyarthritis requiring treatment with systemic corticosteroids and methotrexate. Objective responses were observed in all three patients. CONCLUSIONS: Our case series demonstrates that anti-PD-1 therapy with nivolumab can be highly effective following allogeneic transplant for Hodgkin's lymphoma, but serious immune-related adverse events can occur, requiring very close monitoring and interruption of therapy.
Continuous Treatment of Non-Hodgkin’s Malignant Lymphoma with Prednimustine (Leo 1031)
AbstractThe effect of Prednimustine was evaluated in 37 patients with generalised non-Hodgkin's lymphomas. The patients were divided into three groups according to dosage and previous treatment. Totally, in all three groups, 22 complete and 10 partial remissions were observed. During follow-up, five of the complete responders and all partial responders have relapsed. Leucopenia and thrombocytopenia were induced in several patients, but were always moderate and reversible after withdrawal of the drug. In some patients with a history of peptic ulcer or diabetes mellitus, these conditions were aggravated.
AbstractPURPOSE OF REVIEW: Despite the advances in the treatment of Hodgkin Lymphoma, patients with refractory disease still have a poor prognosis. Hodgkin Lymphoma can be refractory at first diagnosis or might become refractory later in the course of treatment. Both situations represent a therapeutic challenge. RECENT FINDINGS: Intensified chemotherapy with BEACOPP escalated has been evaluated in early unfavourable and advanced Hodgkin Lymphoma and led to an improved tumour control and reduced rates of refractory disease. Furthermore, there is growing evidence for the role of tandem autologous transplant in breaking refractory disease. For patients relapsing after autologous transplant, more recent analyses have reported outcome and defined risk factors. The antibody drug conjugate brentuximab vedotin is a new, highly effective therapeutic option for these patients. Dose-reduced allogeneic transplant is a therapeutic alternative for patients relapsing after autologous transplant, but induction of a remission is the prerequisite for a successful allogeneic transplant. Brentuximab vedotin has been evaluated as a bridge to allogeneic transplant for patients refractory to conventional treatment. SUMMARY: Recent therapeutic advances have improved the prognosis of Hodgkin Lymphoma by prevention or successful treatment of refractory disease. The use of new drugs such as brentuximab vedotin will hopefully further increase the cure rates.
Efficacy and safety of nivolumab in the treatment of relapsed/refractory classical Hodgkin’s lymphoma: Pavlov First Saint Petersburg State Medical University experience
AbstractBackground . Using modern first-line chemotherapy more than 80 % of patients with classical Hodgkin’s lymphoma can be cured, however, in 15–20 % of cases there is a relapsed/refractory disease. The use of nivolumab in international clinical practice has significantly improved treatment results of patients with relapsed/refractory classical Hodgkin’s lymphoma.Objective of this study is to evaluate the results of therapy with nivolumab in the сlinic of Pavlov First Saint Petersburg State Medical University.Materials and methods . The retrospective analysis included treatment results of 101 patients with relapsed/refractory classical Hodgkin’s lymphoma who received nivolumab in Raisa Gorbacheva Memorial Research Institute of Children Oncology, Hematology and Transplantation from February 2016 to August 2018. The group included 90 patients who received nivolumab as part of an named patient program. Therapy response was assessed using CT/PET-CT in accordance with LYRIC criteria for response assessment of malignant lymphomas to immunotherapy. Safety and tolerability were assessed by registering adverse events in accordance with NCI CTCAE version 4.03 criteria. Results . Median follow-up was 25 months. The response was registered in 64 % of patients: in 32 (31.6 %) – complete response and in 33 (32.7 %) – partial response. Stabilization and progression as the best response were registered in 5 (4.9 %) and 10 (9.8 %) patients, respectively. Indeterminate response was observed in 21 (20.6 %) patients. The 2-year overall survival was 96 %; the median of overall survival was not achieved. Progression-free survival (PFS) in studied patients was 40.6 %. The median of PFS was 17.9 months. There were no significant differences in PFS between patients with a partial and indeterminate response. Adverse events were reported in 87.1 % of patients. Severe adverse events (III–IV grade) occur in 18.8 % of patients.Conclusion . The results of a retrospective study of nivolumab therapy in Russian patients with relapsed/refractory classical Hodgkin’s lymphoma are consistent with published international data. Nivolumab demonstrates high efficacy as a monotherapy for relapsed/refractory classical Hodgkin’s lymphoma, regardless of previous therapy type and duration with well tolerance. Pseudo-progression phenomena during immunotherapy require revision of the traditional Hodgkin’s lymphoma therapy response criteria.
Revista médica de Chile · 2023 · 0 citations · open access
Experiencia clínica de uso de Brentuximab-vedotin como terapia de linfoma de Hodgkin recaído o refractario en Hospital Guillermo Grant Benavente, Concepción, Chile
AbstractINTRODUCTION: Hodgkin's lymphoma is a B-cell neoplasm with a good prognosis but a poor response to chemotherapy in refractory or relapsed cases. Brentuximab-vedotin is an anti-CD30 monoclonal antibody approved for use in these cases. This study aims to describe the clinical experience of patients treated with brentuximab-vedotin through expanded access modality. MATERIALS AND METHODS: A retrospective study on clinical information of patients diagnosed with refractory or relapsed Hodgkin's lymphoma treated with brentuximab-vedotin at the Regional Hospital of Concepción in the period 2015-2021. RESULTS: 7 patients were identified, 5/7 male, with a median age of 35 years (21-50). Five cases were mixed cellularity, and two were nodular sclerosis. Four were in stage II, 1/7 in stage III, and 3/7 in stage IV. The median number of previous treatment lines was 4 (3-5), and the relapse was post-transplantation in two cases. In 6/7 cases, brentuximab-vedotin was used as induction, and in one case, it was used as post-autologous bone marrow transplant maintenance. The administration was outpatient via a peripheral route with a median dose of 150 mg and ten cycles. In one case, dose adjustment was required due to toxicity. Three out of 6 patients achieved complete remission and underwent autologous stem cell transplantation. CONCLUSION: brentuximab-vedotin is an outpatient medication with low toxicity that can optimize the treatment of patients with relapsed-refractory Hodgkin's lymphoma.
AbstractHodgkin's disease is a rare lymphoma usually diagnosed in adults presenting with painless lymphadenopathy. Treatment includes radiation therapy for early stages of the disease and chemotherapy for advanced stages. While the majority with Hodgkin's disease will be cured of their disease, patients must complete a period of therapy with risks of significant acute side effects and serious long-term complications. This article provides an overview of the natural history, diagnosis, and staging of Hodgkin's disease as well as a discussion about treatment modalities and associated complications.
Disease module: DeepOracle (Open Targets). Approved indication: ChEMBL drug_indication (max_phase=4). Structures: RDKit from PubChem SMILES. Literature: retrieved by DeepSearch across 234,678,978 indexed works, resolved on OpenAlex.
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