Shyam A. Patel, MD, PhD, is an associate professor at the University of Massachusetts Chan Medical School; as well as a hematologist and oncologist at the UMass Memorial Medical Center.

Dr Patel on the p53 IHC Positivity as Potential Surrogate for Multi-Hit TP53 Mutations in MDS and AML

"It is important to know this information because early identification of multi-hit 

 might change the overall plan or the goals of care for a given patient. For example…patients [with multi-hit 

 status] might benefit from expedited stem cell transplant or from just knowing this prognostic information early on."

Shyam A. Patel, MD, PhD, an associate professor at the University of Massachusetts Chan Medical School and a hematologist and oncologist at the UMass Memorial Medical Center, highlighted findings from a bootstrap analysis designed to determine the optimal p53 immunohistochemistry (IHC) positivity threshold that correlates with multi-hit 

 mutational status in patients with myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML).

The aim of this analysis was to assess whether IHC could serve as a surrogate marker for 

 allelic state, thereby informing risk stratification and guiding early therapeutic decisions, Patel began.

Although the 2022 International Consensus Classification (ICC) provides a clinical framework for defining multi-hit 

 status, it does not fully equate to biallelic 

 disruption, he explained. Therefore, identifying a reproducible and accessible method to infer multi-hit status remains a clinical priority, Patel stated.

Findings from the study showed that, among 82 patients with concurrent IHC and next-generation sequencing (NGS) data, a p53 IHC positivity threshold of 7% was found to best correlate with multi-hit 

 status, Patel reported. Furthermore, increasing p53 IHC positivity was associated with poorer overall survival, supporting its prognostic relevance. Notably, false-negative IHC results occurred exclusively in patients with sole 

 nonsense or frameshift mutations, highlighting a potential limitation in the assay's sensitivity for certain mutation types.

Patel emphasized the clinical implications of early 

 risk identification. Patients found to harbor multi-hit 

 status may be candidates for expedited allogeneic stem cell transplant or other intensive interventions, he added. The ability to stratify patients based on a widely available and relatively low-cost assay like IHC could allow for earlier prognostic discussions and treatment planning, particularly in centers where comprehensive genomic testing may not be readily accessible, Patel noted. These findings support incorporating p53 IHC into initial diagnostic workflows for patients with suspected MDS or AML, Patel concluded.

Videos

Shyam A. Patel, MD, PhD, discusses the threshold of p53 IHC positivity best correlating with multi-hit TP53 mutational status in MDS and AML.

Jonathan M. Gerber, MD, is a member of the faculty in the Department of Medicine at New York University (NYU) Grossman School of Medicine; as well as the chief clinical officer of the NYU Perlmutter Cancer Center. 

, which provides oncology professionals with the resources and information they need to provide the best patient care. In both digital and print formats, OncLive covers every angle of oncology practice, from new technology to treatment advances to important regulatory decisions.

In today’s OncClub episode, we had the pleasure of speaking with Jonathan M. Gerber, MD; and Shyam A. Patel, MD, PhD, about a study they conducted investigating the use of immunohistochemistry (IHC) as a biomarker for early 

 mutation identification in patients with myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). Dr Gerber is a member of the faculty in the Department of Medicine at New York University (NYU) Grossman School of Medicine; as well as the chief clinical officer of the NYU Perlmutter Cancer Center. Dr Patel is an associate professor at the University of Massachusetts Chan Medical School; as well as a hematologist and oncologist at the UMass Memorial Medical Center in Worcester. 

In our exclusive interview, Drs Gerber and Patel discussed the evaluation of p53 IHC as a surrogate biomarker for 

-mutant MDS and AML. They shared how the presence of 

 mutations in these diseases significantly worsens prognosis, necessitating urgent treatment. They also highlighted how IHC results are available within 48 to 72 hours. Gerber and Patel explained this study's design and patient population, as well as how IHC's inverse correlation with overall survival highlights its potential as an early biomarker, though it has lower sensitivity for certain mutations.

 to see additional findings and insights from this research! 
___

That’s all we have for today! Thank you for listening t

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Podcasts

Drs Gerber and Patel discuss a study they conducted investigating the use of IHC as a biomarker for early TP53 mutation identification in MDS and AML.

IHC Testing Leads to Early Detection of TP53-Mutant AML and MDS: With Jonathan M. Gerber, MD; and Shyam A. Patel, MD, PhD

Dr Patel on Second Primary Cancer Prevention Strategies After CAR T-Cell Therapy in Hematologic Malignancies

“One of the components of secondary prevention is identifying patients who have an inherent baseline risk or predisposition to developing SPCs. Another major aspect of secondary prevention includes identifying patients who may have baseline inflammation or comorbidities that might place them at higher risk for developing SPCs.”

Shyam A. Patel, MD, PhD, associate professor, Department of Medicine, UMass Chan Medical School; hematologist/oncologist, UMass Memorial Medical Center, discusses potential secondary prevention strategies for monitoring and mitigating the risk of developing second primary cancers (SPCs) in patients with hematologic malignancies after treatment with CAR T-cell therapy.

Secondary prevention strategies play a critical role in mitigating several of the risks associated with CAR T-cell therapy, particularly the development of SPCs, Patel begins. One of the key secondary prevention strategies is identifying patients who have an inherent baseline risk or predisposition for developing SPCs, he states. This includes patients with pre-existing clonal hematopoiesis, a condition in which a subpopulation of blood cells displays somatic mutations within the hematopoietic compartment, causing a clonal expansion of these mutated cells, Patel details.

These mutations can predispose patients to clonal expansion of the mutated cells, potentially leading to the development of malignancies, especially in the post–CAR T-cell therapy setting, Patel explains. Given this increased risk, it may be prudent to screen patients for baseline clonal hematopoiesis prior to initiating CAR T-cell therapy, he says. However, despite its potential value, there is currently no consensus in the guidelines regarding this approach for secondary SPC prevention, Patel notes.

In addition to clonal hematopoiesis, another significant component of secondary prevention involves identifying patients with baseline inflammation or comorbidities that may elevate their risk of developing SPCs following treatment with CAR T-cell therapy, Patel continues. Overall, secondary prevention efforts should focus on stratifying patients based on their baseline risk factors, including clonal hematopoiesis and other comorbidities, Patel concludes.

Shyam A. Patel, MD, PhD, discusses secondary prevention strategies that may mitigate the risk of developing SPCs after receipt of CAR T-cell therapy.

Dr Patel on Second Primary Cancer Prevention Strategies After CAR T-Cell Therapy

Saurabh Dahiya, MD, FACP, is an associate professor of medicine at Stanford University School of Medicine; as well as clinical director of Cancer Cell Therapy in the Division of Blood and Marrow Transplantation and Cell Therapy at Stanford Medicine

, which provides oncology professionals with the resources and information they need to provide the best patient care. In both digital and print formats, 

 covers every angle of oncology practice, from new technology to treatment advances to important regulatory decisions.

In today’s OncClub episode, we had the pleasure of speaking with Saurabh Dahiya, MD, FACP, and Shyam A. Patel, MD, PhD, about their research into the risk of developing second primary cancers (SPCs) following CAR T-cell therapy and how this risk, though low, may be mitigated. Dr Dahiya is an associate professor of medicine at Stanford University School of Medicine and Clinical Director of Cancer Cell Therapy in the Stanford BMT and Cell Therapy division in Palo Alto, California. Dr Patel is an associate professor in the Department of Medicine at the UMass Chan Medical School, as well as a hematologist/oncologist at UMass Memorial Medical Center in Worcester, Massachusetts.

In our exclusive interview, Drs Dahiya and Patel discussed the pathobiology of SPCs that develop after CAR T-cell therapy, potential SPC prevention strategies, and how SPC research may help optimize CAR T-cell product development in the future.

 to see additional findings and insights from this research! 

That’s all we have for today! Thank you for listening to this episode of 

For more updates in oncology, be sure to visit 

 is also on social media. On X, and BlueSky, follow us at @OncLive. On Facebook, like us at OncLive, and follow our OncLive page on LinkedIn.

*OncLive On Air is available on: Apple Podcasts, Google Podcasts, Spotify, Amazon Music, Audacy, CastBox, Deezer, iHeart, JioSaavn, Listen Notes, Player FM, Podcast Addict, Podchaser, RadioPublic, and TuneIn.

Drs Dahiya and Patel discuss how SPC research may help optimize CAR T-cell product development in the future.

How Second Primary Cancer Risk Factors Into CAR T-Cell Therapy Considerations: With Saurabh Dahiya, MD, FACP; and Shyam A. Patel, MD, PhD

Shyam A. Patel, MD, PhD, discusses the impact of donor-engrafted clonal hematopoiesis on the risk of disease relapse and survival outcomes with allo- and auto-HSCT.

Dr Patel on the Impact of Donor-Engrafted Clonal Hematopoiesis on Outcomes With Auto-/Allo-HSCT

Shyam A. Patel, MD, PhD, assistant professor, University of Massachusetts Chan Medical School, discusses the impact of donor-engrafted clonal hematopoiesis on the risk of disease relapse and survival outcomes with allogeneic and autologous hematopoietic stem cell transplant (allo-HSCT; auto-HSCT) in patients with hematologic malignancies.

Patel and colleagues conducted a comprehensive meta-analysis and meta-regression to evaluate the impact of donor-derived clonal hematopoiesis and pretransplant clonal hematopoesis on patient outcomes with allo-HSCT and auto-HSCT, respectively. The investigation evaluated 9 studies on auto-HSCT and 5 with allo-HSCT.

Results showed distinct effects of donor-derived clonal hematopoiesis on clinical outcomes depending on the type of transplant, Patel begins. For patients who underwent auto-HSCT, the pre-transplant clonal hematopoiesis was associated with poorer outcomes across several clinical parameters, including overall survival (OS), progression-free survival (PFS), and an increased risk of therapy-related neoplasms, he reports. These findings indicate that pre-transplant clonal hematopoiesis is a significant negative prognostic factor in auto-HSCT, potentially due to the superior engraftment potential of mutated hematopoietic stem cells compared to their wild-type counterparts, which may lead to worse overall outcomes, Patel explains.

In contrast, the impact of donor-derived clonal hematopoiesis in allo-HSCT showed a more nuanced effect, Patel continues. Although the presence of clonal hematopoiesis did not significantly affect OS, PFS, or non-relapse mortality, it was associated with a decreased risk of disease relapse, he details. This suggests a potential beneficial role of donor-derived clonal hematopoiesis in the context of allo-HSCT, possibly due to a graft-vs-leukemia (GvL) effect that may enhance the antitumor activity of the graft, Patelsays.

Overall, the study highlights a bimodal effect of clonal hematopoiesis, Patel states. Although it is predictive of inferior outcomes with auto-HSCT, it may provide some protective benefits with allo-HSCT, Patel notes. This distinction underscores the need for tailored approaches in screening for clonal hematopoiesis based on the type of stem cell transplant, he emphasizes. For auto-HSCT, prospective CHIP screening of the donor appears crucial due to its association with adverse outcomes with pre-transplant clonal hematopoesis, whereas the utility of such screening is less clear and may not be as critical for those undergoing allo-HSCT, Patelconcludes.

Shyam A. Patel, MD, PhD

Articles

Dr Patel on the p53 IHC Positivity as Potential Surrogate for Multi-Hit TP53 Mutations in MDS and AML

IHC Testing Leads to Early Detection of TP53-Mutant AML and MDS: With Jonathan M. Gerber, MD; and Shyam A. Patel, MD, PhD

Dr Patel on Second Primary Cancer Prevention Strategies After CAR T-Cell Therapy

How Second Primary Cancer Risk Factors Into CAR T-Cell Therapy Considerations: With Saurabh Dahiya, MD, FACP; and Shyam A. Patel, MD, PhD

Dr Patel on the Impact of Donor-Engrafted Clonal Hematopoiesis on Outcomes With Auto-/Allo-HSCT