^
BIOMARKER:

Chr del(17p)

7d
TP53-altered CLL Treated with Firstline Bruton's Tyrosine Kinase Inhibitor-based Therapy: A Retrospective Analysis. (PubMed, Am J Hematol)
We performed a retrospective analysis of 130 patients with CLL with baseline del(17p) and/or TP53-m treated with BTKi with or without the BCL2 inhibitor venetoclax (VEN) and with or without CD20 antibody in the firstline setting...Del(17p) was identified in <25% of cells in 26/104 (25%) of patients, and 28/101 (28%) of TP53-m were low-burden with a VAF of <10%; outcomes of these patients were similar to those with high-burden lesions. This study suggests that low-burden TP53 alterations should not be ignored when assessing genomic risk in CLL in the era of targeted therapy.
Retrospective data • Journal • IO biomarker
|
TP53 (Tumor protein P53) • IGH (Immunoglobulin Heavy Locus)
|
TP53 mutation • Chr del(17p) • IGH mutation
|
Venclexta (venetoclax)
9d
TP53 GENE MUTATION DIVERSITY IN RUSSIAN PATIENTS WITH B-CELL LYMPHOMAS (EHA 2022)
At the same time, the occurrence of “hot spots” mutations in MCL and FL is also higher than expected. Further studies concerning the type of mutations, their allelic load, and their combination with 17th chromosome lesions in association with disease course are on the way.
Clinical • Tumor Mutational Burden
|
TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden)
|
TP53 mutation • Chr del(17p) • TP53 R175H • TP53 R248Q • TP53 R273H
23d
Chronic Lymphocytic Leukemia: Chemotherapy Free and Other Novel Therapies Including CAR T. (PubMed, Curr Treat Options Oncol)
Drugs that interfere with these pathways, such as ibrutinib, venetoclax, and idelalisib, have improved clinical outcomes. Nevertheless, patients without high-risk features such as TP53 abnormalities also benefit from novel agents. Following relapse, depending on the primary oral agent used, BTK inhibitors, venetoclax in combination with anti-CD20 antibodies, or PI3K inhibitors are preferred.
Review • Journal • IO biomarker
|
TP53 (Tumor protein P53) • BCL2 (B-cell CLL/lymphoma 2) • CD19 (CD19 Molecule) • PLCG2 (Phospholipase C Gamma 2)
|
TP53 mutation • Chr del(17p) • CD19 expression
|
Venclexta (venetoclax) • ibrutinib • Zydelig (idelalisib)
25d
Study of the Use of Venetoclax in Participants With Chronic Lymphocytic Leukemia (CLL) Under Real-Life Setting (clinicaltrials.gov)
P=N/A, N=350, Recruiting, AbbVie | Trial completion date: Dec 2025 --> Dec 2024 | Trial primary completion date: Dec 2025 --> Dec 2024
Trial completion date • Trial primary completion date
|
TP53 (Tumor protein P53)
|
TP53 mutation • Chr del(17p) • TP53 mutation + Chr del(17p)
|
Venclexta (venetoclax)
26d
Study of the Use of Venetoclax in Participants With Chronic Lymphocytic Leukemia (CLL) Under Real-Life Setting (clinicaltrials.gov)
P=N/A, N=350, Recruiting, AbbVie | N=59 --> 350 | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Dec 2025
Enrollment change • Trial completion date • Trial primary completion date
|
TP53 (Tumor protein P53)
|
TP53 mutation • Chr del(17p) • TP53 mutation + Chr del(17p)
|
Venclexta (venetoclax)
2ms
Trial completion date • Combination therapy
|
HLA-DRB1 (Major Histocompatibility Complex, Class II, DR Beta 1)
|
Chr del(17p)
|
bortezomib • sirolimus • melphalan • fludarabine IV • peripheral blood stem cell transplantation • tacrolimus XR • tacrolimus intravenous
2ms
Venetoclax and Eprenetapopt for the Treatment of Relapsed of Refractory Mantle Cell Lymphoma (clinicaltrials.gov)
P2, N=0, Withdrawn, M.D. Anderson Cancer Center | N=20 --> 0 | Not yet recruiting --> Withdrawn
Enrollment change • Trial withdrawal
|
CCND1 (Cyclin D1) • NOTCH2 (Notch 2) • BIRC3 (Baculoviral IAP repeat containing 3) • NSD2 (Nuclear Receptor Binding SET Domain Protein 2)
|
TP53 mutation • Chr del(17p) • TP53 wild-type • TP53 deletion • BIRC3 mutation • CCND1 overexpression • CCND1 mutation
|
Venclexta (venetoclax) • eprenetapopt (APR-246)
2ms
ECT-001 (UM171) Expanded Cord Blood Transplant to Treat High-risk Multiple Myeloma (clinicaltrials.gov)
P1/2, N=20, Active, not recruiting, Ciusss de L'Est de l'Île de Montréal | Recruiting --> Active, not recruiting
Enrollment closed
|
CD34 (CD34 molecule) • CD27
|
Chr del(17p) • C1As
|
cyclophosphamide • melphalan • ECT-001-CB • mycophenolate mofetil
3ms
A large fraction of trisomy 12, 17p, and 11q CLL cases carry unidentified microdeletions of miR-15a/16-1. (PubMed, Proc Natl Acad Sci U S A)
In addition, ∼40% of CLL cases bearing T12, 17p, and 11q showed unidentified microdeletions of miR-15a/16-1, suggesting that miR-15a/16-1 loss cooperates with such chromosomal alterations in CLL. These data may have clinical relevance for the successful stratification of patients for treatment.
Journal • IO biomarker
|
BCL2 (B-cell CLL/lymphoma 2) • MIR15A (MicroRNA 15a)
|
Chr del(17p) • BCL2 overexpression • TS 12
3ms
Clonal and subclonal TP53 molecular impairment is associated with prognosis and progression in multiple myeloma. (PubMed, Blood Cancer J)
Notably, the acquisition of TP53 alterations at relapse dramatically worsened the clinical course of patients. Overall, our analyses showed these techniques to be highly sensitive to identify TP53 aberrations at sub-clonal level, emphasizing the poor prognosis associated with double-hit MM patients.
Journal
|
TP53 (Tumor protein P53)
|
TP53 mutation • Chr del(17p) • TP53 deletion
3ms
Trial suspension • Combination therapy
|
TP53 (Tumor protein P53) • GDF15 (Growth differentiation factor 15) • CD4 (CD4 Molecule)
|
TP53 mutation • Chr del(17p) • TP53 wild-type
|
decitabine • navtemadlin (KRT-232)
4ms
T Cell Depleted Allogeneic Hematopoietic Stem Cell Transplantation Conditioned With a Reduced Intensity Regimen in Patients With Hematologic Malignancies and Aplastic Anemia (clinicaltrials.gov)
P1, N=15, Recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: May 2022 --> May 2023 | Trial primary completion date: May 2022 --> May 2023
Trial completion date • Trial primary completion date
|
TP53 (Tumor protein P53) • FLT3 (Fms-related tyrosine kinase 3) • RUNX1 (RUNX Family Transcription Factor 1) • ASXL1 (ASXL Transcriptional Regulator 1)
|
TP53 mutation • Chr del(17p) • FLT3 mutation • RUNX1 mutation • ASXL1 mutation • Chr t(4;14) • Chr t(14;16)
|
Rituxan (rituximab) • cyclophosphamide • fludarabine IV • Thymoglobulin (anti-thymocyte globulin (rabbit))
4ms
ECT-001 (UM171) Expanded Cord Blood Transplant to Treat High-risk Multiple Myeloma (clinicaltrials.gov)
P1/2, N=20, Recruiting, Ciusss de L'Est de l'Île de Montréal | Trial completion date: Mar 2024 --> Sep 2025 | Trial primary completion date: Mar 2022 --> Sep 2021
Trial completion date • Trial primary completion date
|
CD34 (CD34 molecule) • CD27
|
Chr del(17p) • C1As
|
melphalan • ECT-001-CB • mycophenolate mofetil
4ms
Testing a New Chemotherapy Drug, KRT-232 (AMG-232) in Combination With Decitabine in Patients With Acute Myeloid Leukemia (clinicaltrials.gov)
P1b, N=48, Recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2021 --> Dec 2022 | Trial primary completion date: Dec 2021 --> Dec 2022
Trial completion date • Trial primary completion date • Combination therapy
|
TP53 (Tumor protein P53) • GDF15 (Growth differentiation factor 15) • CD4 (CD4 Molecule)
|
TP53 mutation • Chr del(17p) • TP53 wild-type
|
decitabine • navtemadlin (KRT-232)
5ms
Chronic lymphocytic leukemia: 2022 update on diagnostic and therapeutic procedures. (PubMed, Am J Hematol)
When treatment is indicated, several therapeutic options exist: a combination of the B-cell lymphoma 2 (BCL2) inhibitor venetoclax with obinutuzumab, monotherapy with inhibitors of Bruton tyrosine kinase (BTK) such as ibrutinib and acalabrutinib, or chemoimmunotherapy. Moreover, the optimal sequencing of targeted therapies remains to be determined. A particular challenge of the next few years will be to identify alternative therapies for patients with BTK and BCL2 inhibitor double-refractory disease.
Journal • IO biomarker
|
TP53 (Tumor protein P53) • CD5 (CD5 Molecule)
|
TP53 mutation • Chr del(17p) • TP53 mutation + Chr del(17p)
|
Venclexta (venetoclax) • ibrutinib • Gazyva (obinutuzumab) • Calquence (acalabrutinib)
5ms
Study of the Use of Venetoclax in Patients With Chronic Lymphocytic Leukemia (CLL) Under Real-Life Setting (clinicaltrials.gov)
P=N/A, N=59, Recruiting, AbbVie | Trial completion date: Dec 2025 --> Dec 2024 | Trial primary completion date: Dec 2025 --> Dec 2024
Clinical • Trial completion date • Trial primary completion date
|
TP53 (Tumor protein P53)
|
TP53 mutation • Chr del(17p) • TP53 mutation + Chr del(17p)
|
Venclexta (venetoclax)
5ms
Study of the Use of Venetoclax in Patients With Chronic Lymphocytic Leukemia (CLL) Under Real-Life Setting (clinicaltrials.gov)
P=N/A, N=59, Recruiting, AbbVie | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Dec 2025
Clinical • Trial completion date • Trial primary completion date
|
TP53 (Tumor protein P53)
|
TP53 mutation • Chr del(17p) • TP53 mutation + Chr del(17p)
|
Venclexta (venetoclax)
6ms
ASSURE: Acalabrutinib Safety Study in Untreated and Relapsed or Refractory Chronic Lymphocytic Leukemia Patients (clinicaltrials.gov)
P3b, N=553, Active, not recruiting, AstraZeneca | Recruiting --> Active, not recruiting
Clinical • Enrollment closed
|
TP53 (Tumor protein P53) • CD20 (Membrane Spanning 4-Domains A1) • CD19 (CD19 Molecule) • IGH (Immunoglobulin Heavy Locus) • CD5 (CD5 Molecule) • FCER2 (Fc Fragment Of IgE Receptor II)
|
Chr del(17p) • Chr del(11q) • IGH mutation
|
Calquence (acalabrutinib)
6ms
Enrollment closed
|
MYC (V-myc avian myelocytomatosis viral oncogene homolog) • CD20 (Membrane Spanning 4-Domains A1) • HLA-DRB1 (Major Histocompatibility Complex, Class II, DR Beta 1) • CD4 (CD4 Molecule) • HLA-DQB1 (Major Histocompatibility Complex, Class II, DQ Beta 1) • HLA-B (Major Histocompatibility Complex, Class I, B)
|
Chr del(17p) • Chr del(11q) • CD20 expression
|
Rituxan (rituximab) • bendamustine • fludarabine IV
6ms
Utilization of a Targeted Next Generation Sequencing Assay to Identify Copy Number Alterations in Chronic Lymphocytic Leukemia and Monoclonal B-Cell Lymphocytosis (ASH 2021)
Here we show a high sensitivity, specificity, and NPV when comparing targeted sequencing with FISH. FISH panel testing is widely used in clinical practice to characterize highly prognostic chromosomal abnormalities in CLL. Comprehensive genetic profiling with NGS has become increasingly important in the work up of hematologic malignancies and provides additional prognostic and predictive information, including clinically relevant mutations such as TP53, SF3B1 , and NOTCH1, tumor mutation load and mutations associated with resistance to chemo-immunotherapy and targeted therapies, such as BTK or BCL2 inhibitors, that FISH cannot offer.
Next-generation sequencing • Tumor Mutational Burden • IO biomarker
|
TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • NOTCH1 (Notch 1) • SF3B1 (Splicing Factor 3b Subunit 1) • CD19 (CD19 Molecule) • CD5 (CD5 Molecule)
|
TP53 mutation • Chr del(17p) • ATM mutation • Chr del(11q) • NOTCH1 mutation • SF3B1 mutation • Chr del(13)(q14) • Chr del(17p) + Chr del(11q) • TS 12
6ms
Myelodysplastic/myeloproliferative neoplasms-unclassifiable with isolated isochromosome 17q represents a distinct clinico-biologic subset: a multi-institutional collaborative study from the Bone Marrow Pathology Group. (PubMed, Mod Pathol)
The presence of i(17q) retained independent poor prognostic value in multivariable Cox-regression analysis &lsqb;HR 3.686 (1.17-11.6); P = 0.026] along with splenomegaly. We suggest that MDS/MPN-i(17q) warrants recognition as a distinct subtype within the MDS/MPN-U category based on its unique clinico-biologic features and uniformly poor prognosis.
Clinical • Journal
|
TP53 (Tumor protein P53) • SRSF2 (Serine and arginine rich splicing factor 2) • SETBP1 (SET Binding Protein 1)
|
TP53 mutation • Chr del(17p) • SRSF2 mutation
7ms
Factors Associated with Outcomes Among Refractory/Relapsed TP53-Mutated/Chromosome 17p Deletion Acute B-Cell Lymphoblastic Leukemia (B-ALL) Patients Treated with CD19-Targeted Chimeric Antigen Receptor (CAR)-T Therapy (ASH 2021)
Presence of complex cytogenetics and not bridging into allo-HSCT are two factors affecting the long-term efficacy. Further studies are needed to confirm these results, to improve the clinical management and personalization of treatment approaches for B-ALL patients harboring TP53 mutation/chromosome 17p deletion.
Clinical • IO biomarker
|
TP53 (Tumor protein P53) • CD19 (CD19 Molecule)
|
TP53 mutation • Chr del(17p)
7ms
Real-World Treatment Patterns and Outcomes of Patients with Chronic Lymphocytic Leukemia (CLL) Receiving First-Line (1L) Therapy in the United States (US) (ASH 2021)
This analysis provides the current state of 1L CLL testing and treatment patterns and outcomes in the US from 2015 to 2020. As expected, the use of novel targeted oral agents increased over time, with a corresponding increase in TTNTD. Clinical outcomes were improved in patients receiving novel targeted oral agents, both overall and in high-risk subgroups.
Clinical • HEOR • Real-world evidence • IO biomarker
|
IGH (Immunoglobulin Heavy Locus)
|
Chr del(17p) • IGH mutation
7ms
Real-World Evidence on Therapeutic Strategies and Treatment-Sequencing in Patients with Chronic Lymphocytic Leukemia: An International Study of Eric, the European Research Initiative on CLL (ASH 2021)
Regarding novel targeted agents, 1860/9173 (20.2%) patients had received at least one line of treatment with BTKi (ibrutinib, n=1788; acalabrutinib, n=72) over the disease course; 631/9173 (6.9%) with venetoclax; and, 447/9173 (4.9%) with the PI3K inhibitor idelalisib...The great majority (865/1086 cases, 79.7%) of patients who received a second line before 2014 were retreated with CIT, most commonly Bendamustine-Rituximab (284/1086, 26.1%) and Fludarabine-Cyclophosphamide-Rituximab (252/1086, 23.2%); alemtuzumab monotherapy was used in 55/1086 (5%) of patients...Patients treated with CIT (n=694) had an ORR of 68.7% (28.3% CR+40.4% PR). In conclusion, in a large international study we provide real world data regarding the selection and sequencing of treatment in CLL, charting a major shift in treatment patterns before and after the Introduction of novel trargeted agents and confirming their efficacy even in high-risk CLL.
Clinical • HEOR • Real-world evidence • IO biomarker
|
TP53 (Tumor protein P53) • BCL2 (B-cell CLL/lymphoma 2) • IGH (Immunoglobulin Heavy Locus)
|
TP53 mutation • Chr del(17p)
|
Venclexta (venetoclax) • Rituxan (rituximab) • ibrutinib • cyclophosphamide • Zydelig (idelalisib) • Calquence (acalabrutinib) • Campath (alemtuzumab) • bendamustine • fludarabine IV
7ms
Clinical Significance of Spatial Heterogeneity in Newly Diagnosed and Relapsed Multiple Myeloma (ASH 2021)
In a patient in complete response (CR) after 5 cycles RVD (Lenalidomide, Bortezomib, Dexamethasone), autologous stem cell transplant (ASCT) and 5 years of lenalidomide maintenance, follow-up PET/CT showed a single new FL in the caudal right ilium. Our findings showing divergent results from MRD assessments in bone marrow and FL underline the critical role of whole-body imaging for follow-up of patients in remission. Sampling plasma cells solely from the IC limits the ability for complete clinical decision-making.
Clinical
|
TP53 (Tumor protein P53) • SDC1 (Syndecan 1)
|
TP53 mutation • Chr del(17p)
|
lenalidomide • bortezomib • dexamethasone
7ms
Normal FISH CLL Represents a Heterogeneous Subgroup Where Prognosis Can be Refined with IGHV Mutational Status (ASH 2021)
Additional cytogenetic testing demonstrates alternative genetic alterations are common in normal 12/13/11/17 CLL pts, however, our data do not show that these alterations are significant independent predictors of TTFT or OS. While normal FISH CLL is a relatively heterogeneous group, pts with mutated IGHV represent a subset of pts with very low risk disease.
TP53 (Tumor protein P53) • CDKN2A (Cyclin-dependent kinase inhibitor 2A) • IGH (Immunoglobulin Heavy Locus) • BCL6 (B-cell CLL/lymphoma 6) • B2M (Beta-2-microglobulin)
|
Chr del(17p) • CDKN2A deletion • IGH mutation • MYC rearrangement • BCL6 rearrangement • TS 12
7ms
16p Deletion Involving BCMA Locus Is Frequent and Predominantly Observed with del17p (ASH 2021)
Our results also highlight that BCMA expressions in bulk sample may not detect the presence or absence of cells with target loss and therefore combining strategies at bulk and single cell level are necessary to understand the disease status. These results suggest the need to study del16p in patients being targeted for BCMA-directed therapy and its association with other risk factors in MM.
Tumor Mutational Burden • IO biomarker
|
TMB (Tumor Mutational Burden) • CDKN2C (Cyclin Dependent Kinase Inhibitor 2C)
|
TP53 mutation • Chr del(17p) • TP53 deletion
7ms
Zanubrutinib in Combination with Venetoclax for Patients with Treatment-Naïve (TN) Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL) with del(17p): Early Results from Arm D of the SEQUOIA (BGB-3111-304) Trial (ASH 2021)
Preliminary safety data with the 9.7-mo median follow-up suggest that zanubrutinib + venetoclax was generally well tolerated in this high-risk population, with no new safety signals identified and no TLS reported. Enrollment is ongoing; updated safety, efficacy, and biomarker data will be presented.
Clinical • Combination therapy • IO biomarker
|
BCL2 (B-cell CLL/lymphoma 2) • IGH (Immunoglobulin Heavy Locus)
|
Chr del(17p) • IGH mutation • Chr del(17)(p13.1)
|
Venclexta (venetoclax) • Brukinsa (zanubrutinib)
7ms
[VIRTUAL] EVALUATION OF CONVENTIONAL KARYOTYPE AND IN SITU HYBRIDATION BY FLUORESCENCE IN PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA NOT MUTTED TO THE IGHV GENE (HEMO 2021)
Introduction The search for somatic hypermutation of the IGHV gene, together with karyotype analysis and fluorescence in situ hybridization (FISH), are valuable resources for the prognostic stratification in chronic lymphocytic leukemia (CLL). About 80% of CLL cases have genetic alterations that correlate with prognosis.Objective To correlate alterations detected by karyotype and FISH in patients not mutated to the IGHV gene and to evaluate the importance of combining these findings.Methodology Thirty blood samples were analyzed peripheral or bone marrow of patients with CLL. Molecular testing for IGHV was performed by reverse transcription and amplification of the mRNA corresponding to the IGHV gene, followed by sequencing and database comparison. Karyotyping was performed by means of culture stimulated with mitogens B and/or oligo, and FISH used probes for MY B, cen12, IGH, RB1, ATM and TP53. Result 7 (23.33%) patients had complex karyotype ( ≥3 changes) and abnormal FISH that complemented each other; 7 (23.33%) patients had trisomy 12 in both tests; 5 (16.67%) demonstrated a normal karyotype with altered FISH (deletion of the MYB, TP53 and trisomy 12 genes). In 1 (3.33%) the 17p deletion was detected simultaneously in both tests; 1 (3.33%) had a rearrangement involving the long arm of chromosome 17; 4 (13.33%) had alterations involving one of the chromosomes: 4, 6, 11, 13 and 14 and one of the genes: MYB, ATM, RB1 and IGH. In 5 cases (16.67%), it was not possible to obtain viable metaphases in the karyotype, however FISH detected alterations involving one of the genes: ATM, RB1, IGH, TP53 and trisomy of chromosome 12.Conclusion Karyotype, FISH and IGHV carried out, simultaneously, showed relevant data for the prognostic stratification of patients with CLL. More than 50% of the detected alterations, both those found in the karyotype, such as cases with complex karyotype, and other alterations considered only in FISH, corroborated the literature, showing that they are equally unfavorable and of aggressive course, as is the case with presence of the non-mutated IGHV gene.
Clinical
|
TP53 (Tumor protein P53) • ATM (ATM serine/threonine kinase) • RB1 (RB Transcriptional Corepressor 1) • IGH (Immunoglobulin Heavy Locus)
|
Chr del(17p) • TS 12
9ms
Cytogenetic and molecular abnormalities in Waldenström's macroglobulinemia patients: correlations and prognostic impact. (PubMed, Am J Hematol)
These same factors as well as IPSSWM, tri4, CXCR4 frameshift and SPI1 mutations were significantly associated with lower OS (P<0.05). These results argue for integration of both cytogenetic and molecular screening in evaluation of first-line WM patients.
Clinical • Journal
|
TP53 (Tumor protein P53) • ARID1A (AT-rich interaction domain 1A) • MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • CXCR4 (Chemokine (C-X-C motif) receptor 4) • KMT2D (Lysine Methyltransferase 2D) • MLL2 (Myeloid/lymphoid or mixed-lineage leukemia 2) • SPI1 (Spi-1 Proto-Oncogene)
|
TP53 mutation • Chr del(17p) • KMT2D mutation • MYD88 mutation • CXCR4 mutation
10ms
Clinical • New P2 trial
|
CCND1 (Cyclin D1) • NOTCH2 (Notch 2) • BIRC3 (Baculoviral IAP repeat containing 3)
|
TP53 mutation • Chr del(17p) • TP53 deletion • BIRC3 mutation • CCND1 overexpression • CCND1 mutation
|
Venclexta (venetoclax) • eprenetapopt (APR-246)
11ms
Potential Biomarkers for Treatment Response to the BCL-2 Inhibitor Venetoclax: State of the Art and Future Directions. (PubMed, Cancers (Basel))
Moreover, various potential genetic biomarkers of venetoclax resistance have been proposed, including chromosome 17p deletion, trisomy 12, and TP53 loss or mutation. This manuscript provides an overview of biomarkers that could predict treatment response to venetoclax.
Review • Journal • IO biomarker
|
TP53 (Tumor protein P53)
|
TP53 mutation • Chr del(17p) • TS 12
|
Venclexta (venetoclax)
11ms
Haploidentical Stem Cell Transplant With Prophylactic Natural Killer DLI for Lymphoma, Multiple Myeloma, and CLL (clinicaltrials.gov)
P1, N=30, Recruiting, Noah Merin | Trial completion date: May 2023 --> May 2024 | Trial primary completion date: May 2021 --> May 2022
Trial completion date • Trial primary completion date
|
MYC (V-myc avian myelocytomatosis viral oncogene homolog) • CD20 (Membrane Spanning 4-Domains A1) • HLA-DRB1 (Major Histocompatibility Complex, Class II, DR Beta 1) • CD4 (CD4 Molecule)
|
Chr del(17p) • Chr del(11q) • CD20 expression
|
Rituxan (rituximab) • bendamustine • fludarabine IV
11ms
TP53 disruption in chronic lymphocytic leukemia under ibrutinib: more is worse? (PubMed, Clin Cancer Res)
Chronic lymphocytic leukemia patients carrying a single TP53 hit (chromosome 17p deletion or single TP53 mutation) demonstrate excellent progression-free and overall survival on ibrutinib compared to cases harboring multiple TP53 hits. Testing TP53 deletion/mutation combining FISH and deep next-generation sequencing should be performed for a correct patient evaluation.
Journal
|
TP53 (Tumor protein P53)
|
TP53 mutation • Chr del(17p) • TP53 deletion
|
ibrutinib
12ms
T Cell Depleted Allogeneic Hematopoietic Stem Cell Transplantation Conditioned With a Reduced Intensity Regimen in Patients With Hematologic Malignancies and Aplastic Anemia (clinicaltrials.gov)
P1, N=15, Recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: May 2021 --> May 2022 | Trial primary completion date: May 2021 --> May 2022
Clinical • Trial completion date • Trial primary completion date
|
TP53 (Tumor protein P53) • FLT3 (Fms-related tyrosine kinase 3) • RUNX1 (RUNX Family Transcription Factor 1) • ASXL1 (ASXL Transcriptional Regulator 1)
|
TP53 mutation • Chr del(17p) • FLT3 mutation • RUNX1 mutation • ASXL1 mutation • Chr t(4;14) • Chr t(14;16)
|
Rituxan (rituximab) • fludarabine IV • Thymoglobulin (anti-thymocyte globulin (rabbit))
1year
Clinical • Enrollment change
|
TP53 (Tumor protein P53)
|
TP53 mutation • Chr del(17p) • TP53 mutation + Chr del(17p)
|
Venclexta (venetoclax)
1year
[VIRTUAL] DECIPHERING CLINICAL IMPLICATION OF DYSREGULATED SERUM MICRORNAS IN NEWLY DIAGNOSED MULTIPLE MYELOMA: A RESULT OF COMPREHENSIVE MICRORNA PROFILING BY DEEP SEQUENCING (EHA 2021)
We also report unique miRNAs associated with patients with high tumor burden MM (clonal-PC>95%). Thus, in addition to prognostication and risk stratification, our data demonstrated the value of serum microRNAs in predicting initial response to Bortezomib-based treatment in NDMM.
Clinical
|
MIR199A1 (MicroRNA 199a-1) • MIR328 (MicroRNA 328) • MIR370 (MicroRNA 370) • MIR625 (MicroRNA 625) • MIR769 (MicroRNA 769) • miR-185 (MicroRNA 185) • MIR148A (MicroRNA 148a) • MIR214 (MicroRNA 214) • MIR29A (MicroRNA 29a)
|
Chr del(17p)
|
bortezomib
1year
Clinical • Enrollment open • Combination therapy
|
TP53 (Tumor protein P53) • GDF15 (Growth differentiation factor 15) • CD4 (CD4 Molecule)
|
TP53 mutation • Chr del(17p)
|
decitabine • navtemadlin (KRT-232)
1year
[VIRTUAL] GENOMIC ANALYSIS AND PRECISION THERAPY FOR RECURRENT AND RESISTANT SARCOMA (ASPHO 2021)
Genomic sequencing of refractory/relapsed sarcomas showed a low mutation burden. RNA analysis resulted in identification of potential novel therapeutic targets. Further analysis of patient molecular subgroups and therapeutic strategies is ongoing.
Tumor Mutational Burden
|
TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • RB1 (RB Transcriptional Corepressor 1) • WT1 (WT1 Transcription Factor) • EWSR1 (EWS RNA Binding Protein 1) • FOXO1 (Forkhead box O1) • FLI1 (Fli-1 Proto-Oncogene ETS Transcription Factor) • SS18 (SS18 Subunit Of BAF Chromatin Remodeling Complex) • HMGA2 (High mobility group AT-hook 2)
|
TP53 mutation • Chr del(17p) • MYC amplification • TMB-L • RB1 deletion • EWSR1-FLI1 fusion
1year
Study of the Use of Venetoclax in Patients With Chronic Lymphocytic Leukemia (CLL) Under Real-Life Setting (clinicaltrials.gov)
P=N/A, N=250, Recruiting, AbbVie | Trial completion date: Dec 2022 --> Dec 2024 | Trial primary completion date: Dec 2022 --> Dec 2024
Clinical • Trial completion date • Trial primary completion date
|
TP53 (Tumor protein P53)
|
TP53 mutation • Chr del(17p) • TP53 mutation + Chr del(17p)
|
Venclexta (venetoclax)
1year
Clinical • Trial completion date • Combination therapy
|
HLA-DRB1 (Major Histocompatibility Complex, Class II, DR Beta 1)
|
Chr del(17p)
|
bortezomib • sirolimus • melphalan • fludarabine IV • peripheral blood stem cell transplantation • tacrolimus XR • tacrolimus intravenous
over1year
GAS7 Deficiency Promotes Metastasis in MYCN-driven Neuroblastoma. (PubMed, Cancer Res)
Analysis of expression profiles and the ultrastructure of zebrafish NB tumors with MYCN overexpression identified that GAS7 deficiency led to (i) downregulation of genes involved in cell-cell interaction, (ii) loss of contact among tumor cells as critical determinants of accelerated metastasis, and (iii) increased levels of MYCN protein. These results provide the first genetic evidence that GAS7 depletion is a critical early step in the cascade of events culminating in NB metastasis in the context of MYCN overexpression.
Journal
|
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • GAS7 (Growth Arrest Specific 7)
|
Chr del(17p) • MYCN amplification
over1year
Successful treatment with silver nitrate chemical cauterization for paronychia and granulation in a patient with chronic lymphocytic leukemia undergoing ibrutinib therapy (PubMed, Rinsho Ketsueki)
In February 2019, paronychia (grade 1) developed in the patient's right foot's first toe; hence, topical gentamicin and taping therapy were performed. In July 2019, paronychia/granulation (grade 2) was aggravated and successfully treated with silver nitrate chemical cauterization and taping therapy. The patient was continuously treated with 420 mg/day IBR without dose reduction or discontinuation, resulting in successful disease control of CLL with del 17p.
Clinical • Journal
|
EGFR (Epidermal growth factor receptor)
|
Chr del(17p)
|
ibrutinib • gentamicin sulfate
over1year
[VIRTUAL] De Novo and Therapy-Related Pure Erythroid Leukemia Harbor Distinct TP53 Genetic Alterations (USCAP 2021)
The de novo PEL group had >1 TP53 mutation, hotspot TP53 mutations, and less common TP53 LOH compared to t-PEL. TP53 hotspot mutation in t-PEL were only observed in the presence of a strong predisposing condition. Overall, these findings show distinct TP53 genetic alterations in de novo PEL and t-PEL, possibly reflecting different selective fitness advantages associated with TP53 dysregulation.
BRCA Biomarker
|
TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset)
|
TP53 mutation • BRCA1 mutation • Chr del(17p) • TP53 R175H
over1year
KRT-232 (AMG-232) and Decitabine in Treating Patients With Relapsed, Refractory, or Newly-Diagnosed Acute Myeloid Leukemia (clinicaltrials.gov)
P1b, N=58, Suspended, National Cancer Institute (NCI) | Trial completion date: Dec 2020 --> Dec 2021 | Trial primary completion date: Dec 2020 --> Dec 2021
Clinical • Trial completion date • Trial primary completion date • Combination therapy
|
TP53 (Tumor protein P53) • GDF15 (Growth differentiation factor 15) • CD4 (CD4 Molecule)
|
TP53 mutation • Chr del(17p)
|
decitabine • navtemadlin (KRT-232)
over1year
Combination Chemotherapy and Donor Stem Cell Transplant Followed by Ixazomib Citrate Maintenance Therapy in Treating Patients With Relapsed High-Risk Multiple Myeloma (clinicaltrials.gov)
P1, N=11, Completed, OHSU Knight Cancer Institute | Active, not recruiting --> Completed | Trial completion date: Jul 2021 --> Sep 2020
Clinical • Trial completion • Trial completion date
|
HLA-DRB1 (Major Histocompatibility Complex, Class II, DR Beta 1)
|
Chr del(17p)
|
cytarabine • etoposide IV • Ninlaro (ixazomib) • methotrexate • carmustine • melphalan • methotrexate IV • tacrolimus intravenous • tacrolimus oral
over1year
New P1 trial • Combination therapy
|
HLA-DRB1 (Major Histocompatibility Complex, Class II, DR Beta 1)
|
Chr del(17p)
|
fludarabine IV
almost2years
Study of the Use of Venetoclax in Patients With Chronic Lymphocytic Leukemia (CLL) Under Real-Life Setting (clinicaltrials.gov)
P=N/A, N=250, Recruiting, AbbVie | Trial completion date: Dec 2021 --> Dec 2022 | Trial primary completion date: Dec 2021 --> Dec 2022
Clinical • Trial completion date • Trial primary completion date
|
TP53 (Tumor protein P53)
|
TP53 mutation • Chr del(17p) • TP53 mutation + Chr del(17p)
|
Venclexta (venetoclax)
over2years
T Cell Depleted Allogeneic Hematopoietic Stem Cell Transplantation Conditioned With a Reduced Intensity Regimen in Patients With Hematologic Malignancies and Aplastic Anemia (clinicaltrials.gov)
P1, N=15, Recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: May 2020 --> May 2021 | Trial primary completion date: May 2020 --> May 2021
Clinical • Trial completion date • Trial primary completion date
|
TP53 (Tumor protein P53) • FLT3 (Fms-related tyrosine kinase 3) • RUNX1 (RUNX Family Transcription Factor 1) • ASXL1 (ASXL Transcriptional Regulator 1)
|
TP53 mutation • Chr del(17p) • FLT3 mutation • RUNX1 mutation • ASXL1 mutation • Chr t(4;14) • Chr t(14;16)
|
Rituxan (rituximab) • fludarabine IV • Thymoglobulin (anti-thymocyte globulin (rabbit))