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Karen M. Winkfield, MD, PhD; Narjust Florez, MD, FASCO; Gilberto de Lima Lopes Junior, MD, MBA, FASCO; Coral Olazagasti, MD; Vonetta M. Williams, MD, PhD

 Fighting Disparities and Saving Lives: An Exploration of Challenges and Solutions in Cancer Care

During a Case-Based Roundtable® event, Andrew M. Brunner, MD, discussed dosing strategy for erythropoiesis-stimulating agents as well as dose modifications and safety for the novel agents imetelstat and luspatercept. 

Brunner Discusses Dosing Approaches for ESA and Novel Therapies for Low-Risk MDS

The FDA granted fast track designation to NX-5948 for treating relapsed/refractory Waldenström macroglobulinemia after 2 or more lines of therapy, including a BTK inhibitor.

FDA Grants NX-5948 Fast Track Designation in R/R Waldenström Macroglobulinemia

Here are some of the highlights from this year's 2024 ASH Annual Meeting & Exposition.

Promising Advances in Hematology: Key Findings From ASH 2024

Memorial Sloan Kettering Cancer Center physicians describe challenges in diagnosis, patient care, and the potential expansion of telehealth in this continuation of November's coverfeature.

Multidisciplinary GVHD Care Reveals Unmet Needs and Opportunities

Fixed-duration, subcutaneous epcoritamab-bysp achieved durable responses with a manageable safety profile in older patients with newly diagnosed large B-cell lymphoma who are not candidates for anthracycline-based therapy.

Epcoritamab Delivers Durable Responses in Anthracycline-Ineligible LBCL

AI's Role in Differentiating MDS and Pre-MDS at ASH 2024

Palak Dave, a postdoctoral fellow at Moffitt Cancer Center and Research Institute, discusses the diagnostic challenges between myelodysplastic syndrome (MDS) and pre-MDS conditions, such as idiopathic cytopenia of undetermined significance (ICUS) and clonal cytopenia of undetermined significance (CCUS).


While pre-MDS conditions exhibit abnormalities similar to MDS, their severity is not as pronounced. The manual diagnosis of these conditions is often hindered by subjectivity, leading to variability in how patients are categorized. This inconsistency can result in different classifications for similar cases, making the diagnosis challenging and unreliable.

In response, Dave presents a study to be discussed at the 2024 American Society of Hematology (ASH) Annual Meeting and Exposition. The research explores the use of artificial intelligence (AI) to standardize and accelerate the diagnosis of MDS and pre-MDS conditions.

The AI approach employs deep learning to distinguish MDS from pre-MDS by analyzing bone marrow aspirate smear images alone, without relying on additional clinical data, genetic tests, or other inputs. The study aims to evaluate how effectively this method can differentiate between the conditions based solely on pathology images, potentially leading to more consistent and accurate diagnoses. This innovative use of AI could improve the diagnostic process and help clinicians make more reliable decisions for patients.



The main difference between MDS and pre-MDS conditions lies in the threshold of abnormalities. In pre-MDS conditions, such as ICUS and CCUS, they do have abnormalities similar to MDS, but not as high as MDS. When they analyze these things manually, there are challenges, [particularly due to] subjectivity. This subjectivity can result in variability, potentially causing a patient to be categorized differently. To address this, we are working to standardize the process to ensure more consistent and reliable classification.

It is a deep learning approach designed to automatically distinguish MDS from pre-MDS conditions using only bone marrow aspirate smear images. No additional clinical data, genetic testing, or other inputs are involved—just image data. The goal is to explore how accurately this method can perform using only pathology images.

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Palak Dave discusses the diagnostic challenges between myelodysplastic syndrome and pre-MDS conditions.

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Breaking Down T-Cell Therapies: TCR and CAR T Mechanisms

Paulina Velasquez, MD, assistant faculty member, St. Jude Children’s Research Hospital, discusses the differences between T-cell receptor (TCR)-based and chimeric antigen receptor (CAR) T-cell therapies.

 but differ significantly in their mechanisms and antigen recognition capabilities. TCR-based T cells are MHC-dependent, meaning they are limited to treating patients with specific MHC types. They can recognize both intracellular and cell surface antigens by associating with MHC, providing a broad range of targets. Their exclusive specificity minimizes off-target effects. However, TCR T cells lack additional co-stimulatory signals, which can limit their expansion but reduce the likelihood of exhaustion, making them potentially longer-lasting.

In contrast, CAR T cells are MHC-independent, enabling them to treat a broader patient population regardless of MHC type. They primarily target cell surface antigens and incorporate co-stimulatory domains, which promote greater expansion and persistence of T cells. However, the increased activation and persistence can also lead to higher rates of T cell exhaustion, potentially reducing their long-term effectiveness.

Each approach offers unique advantages and limitations. TCR-based therapies are versatile in antigen recognition but restricted to certain populations and may not expand as effectively. CAR T cells offer broader accessibility and better initial expansion but face challenges with exhaustion and antigen specificity. The balance between these factors guides the choice of therapy based on the clinical scenario.

 Talking about T-cell–based cell therapies, there are 2 different strategies that are the mainstay at the moment, one being TCR–based T-cell therapies and the other ones being chimeric antigen receptor–based T-cell therapies.

Those 2 strategies use T cells, and although they have similarities, when you think about the way they work, they differ in what antigen is being recognized. For example, one strategy, the TCR-based strategy, is MHC-dependent. So it is going to work for just a certain group of people.

CAR T cells, on the other hand, operate through an MHC-independent mechanism. This is advantageous because it removes the limitation to a certain population. However, they are mostly limited to targeting cell surface antigens. CAR T cells do have additional co-stimulation, which allows them to persist longer and expand better. But at the same time, as mentioned, the flip side is that they can become more exhausted, which can impact their effectiveness.

This transcription has been edited for clarity with AI.

Paulina Velasquez, MD, discusses the differences between T-cell receptor-based and chimeric antigen receptor T-cell therapies.

Merryman Discusses the Role of MRD in Lymphoma Care and Trials

Reid Merryman, MD, clinical investigator and assistant professor at Dana-Farber Cancer Institute, discusses which patients are typically monitored for minimal residual disease (MRD) and whether there are specific subtypes or stages where the assessment is particularly critical.

In addition, Merryman explains how MRD is currently being used in clinical trials.

I would say for lymphoma, if we take out [chronic lymphocytic leukemia (CLL)] for lymphoma right now, MRD is not a standard part of clinical practice. We really need prospective, randomized, phase 3 trials to let us know how best to use MRD to guide treatment. So, outside of trials and clinics, I am not testing MRD for my [patients with] lymphoma.

So, I think we are seeing a lot of trials tracking MRD. I would say that almost all trials now are building a collection of plasma samples so that they can look and see how MRD changes with treatment. And we are just starting to see trials that are using MRD to guide therapies. I think there are a few different ways that MRD can be used. So, we can look at changes in MRD at an early time point and then use that to either deescalate therapy or escalate therapy, depending on the MRD status, or, we can use it to guide consolidation, like that mantle cell lymphoma trial I talked about. So, at the end of treatment, we can look at MRD results and we can decide whether we should or should not do additional treatment. There are also some trials that are testing MRD serially and using that to decide when we can stop treatment, and in some cases, when we should restart treatment if MRD emerges. Those are kind of 3 patterns of trials for how to use MRD.

Reid Merryman, MD, discusses which patients are typically monitored for minimal residual disease and whether there are specific subtypes or stages where the assessment is particularly critical.


Erba Explores myeloMATCH Substudies Targeting Genetic Diversity in AML, MDS

Harry Erba, MD, PhD, professor of medicine at Duke Cancer Institute, chair of the SWOG Leukemia Committee, and co-chair of the myeloMATCH Senior Science Council, discusses the specific substudies included in myeloMATCH, a trial representing a significant shift in how acute myeloid leukemia (AML) is treated by addressing the disease's complexity and genetic diversity.

In order to improve outcomes for [patients] with acute myeloid leukemia and myelodysplastic syndromes [MDS], it is critical that we understand the heterogeneity of this patient population in terms of the drivers of the disease pathogenesis. We have a lot of information about the mutations that are present in patients with AML and MDS.

 Out of the 10s of 1000s of genes in each of our cells, there is only a handful, maybe 50 to 60, that are currently mutated in people with acute myeloid leukemia, and they fall into very distinct classes, such as splicing mutations, chromatin modifiers, DNA methylation, enzymes activating signals, transcription factors, cohesin molecules, and such. We truly believe that these mutations underlie a pathogenesis of the disease. We have already started to make great inroads into the treatment of acute myeloid leukemia by identifying some of these targets.

Some of the targets identified are more common like 

ther mutations are now targets for other therapies, such as the Menin inhibitors and patients with 

. myeloMATCH attempts to identify these mutations at the time of diagnosis and then assign patients to clinical trials meant to optimize the initial therapy and then subsequent therapy for these patients based on this mutational analysis.

 myeloMATCH activated on May 16, 2024, and we already have patients accrued to the study. The idea here is that after a patient is screened and the genetic profile is defined, the patient will then be assigned to an appropriate study. Now, we plan to have studies for every subtype that we identified and plan to develop studies for new targets that are identified. But at this point, myeloMATCH is activating with 2 studies: 1 from the Canadian Cancer Trials Group in intermediate-risk AML as defined by [European LeukemiaNet (ELN)] 2017 criteria, and a SWOG study of high-risk, poor-risk, or average-risk karyotype AML as defined by ELN 2017.

 There are other studies coming. We are developing studies for 

, for core binding factors, and those studies are coming for the initial treatment of younger patients with acute myeloid leukemia. We are doing a similar thing for older patients, identifying these mutations and then developing trials.

Harry Erba, MD, PhD, discusses the specific substudies included in myeloMATCH.

Incorporating Immunotherapy Into Hodgkin Lymphoma Treatment Strategies

Stephen M. Ansell, MD, PhD, chair of the Division of Hematology at Mayo Clinic in Rochester, Minnesota, discusses how immunotherapy is being integrated into treatment for patients with advanced stage Hodgkin lymphoma.


Additionally, he explains how the treatment for these patients is becoming more personalized.

One of the regimens, the nivolumab [Opdivo]/AVD [doxorubicin, vinblastine, and dacarbazine]/chemotherapy, has an immune checkpoint blocking antibody, the nivolumab right in the combination, but I think more broadly, PD-1 blockade and agents such as pembrolizumab or nivolumab have really been broadly used in patients with Hodgkin lymphoma, many in the post transplant relapse setting and then subsequently in the salvage treatment combinations before going to a transplant. And now, as I mentioned in the frontline therapy. And the advantages are that you can see benefits for patients in each of these scenarios. In fact, interesting data suggests that using a PD-1 blocking antibody before intensive treatment like a stem cell transplant actually results in significantly greater benefit, suggesting that we are doing something immunological when we do that, that kind of treatment

 I think in many respects, the personalization is really focused on the patient's frailty vs, shall we say, robustness to tolerate treatment. One of the things that has been very interesting is that nivolumab, AVD, and chemotherapy is very well-tolerated in elderly patients. One of the problems with Hodgkin lymphoma is that elderly patients have really been very difficult to treat, purely because of the challenges they have tolerating these treatments. But the use of nivolumab and AVD has actually shown that regimen can be well-tolerated.

Similarly, using brentuximab [vedotin; Adcetris]/AVD, by doing the brentuximab alone first and then the rest of the regimen, has also shown that you can give that to elderly patients. So the personalization is not personalized to the point of understanding the tumor biology. It is more personalized to the understanding of the patient and their needs.

Stephen M. Ansell, MD, PhD, discusses how immunotherapy is being integrated into treatment for patients with advanced stage Hodgkin lymphoma.


Optimizing Treatment Decisions for Patients With CML

Michael J. Mauro, MD, director of the chronic myeloid leukemia (CML) program in the leukemia service at Memorial Sloan Kettering Cancer Center, discusses decision-making for patients with chronic myeloid leukemia (CML).

CML is a complex disease and according to Mauro, decision-making often depends on the stage at diagnosis. He explains that it is crucial to carefully assess both the disease and the patient's overall health, including comorbidities, to find the best treatment plan that offers the highest benefit with the lowest risk.

Mauro shares that treatment should be practical and experts must ensure that patients are not denied the possibility of a curative approach due to fears of adverse events or uncertainty. With multiple therapies available for the treatment of CML, experts can make adjustments based on patient response. As a result, Mauro believes that cure should remain a potential goal for all patients.

 Decision-making for a [patient with] CML can be complicated, depending on the state on the stage you are at when a patient [with CML] is first diagnosed. That is probably the most important point: to sort of do it right [by] looking at all the factors, [including] the disease itself and the patient in great detail–their health, comorbidities, and what is best for them. The [goal should be] to have the highest yield and the lowest risk, to achieve the best response, to probably be practical with milestones and goals of therapy without shortchanging the patient's meaning. Let us not exclude the possibility of a curative approach for all patients with CML or an optimum approach simply based on fear of adverse events or uncertainty.

The good thing is, we have multiple therapies available, so switching and optimization based on the patient’s response can really make headway, [even] if we do not see exactly the perfect trajectory. And again, I think, hopefully, a cure can still be at least a considered goal for all patients.

Michael J. Mauro, MD, discusses decision-making for patients with chronic myeloid leukemia.

Investigational Studies and Therapies in MDS 

David Sallman, MD, myeloid section head and associate member of the Malignant Hematology Department, H. Lee Moffitt Cancer Center and Research Institute, discusses some of the innovative therapies and strategies being investigated in myelodysplastic syndromes (MDS) studies.

 The 1 trial we are maybe most eagerly awaiting for is the VERONA trial [NCT04401748], which is a phase 3 trial of azacitidine with venetoclax versus azacitidine therapy alone. Of course, in AML, this has very much changed the standard-of-care for elderly AML, although it is impacting many patients in all different situations. So, it is a relatively similar type design. I think in MDS, we know that the cytopenia toxicities are a little bit less well tolerated, and thus, we have a lower schedule of venetoclax. There has been a large phase 1, borderline phase 2 study presented by Jacqueline Garcia, MD, at ASH where there are 107 patients, and response rates, at least from composite [complete] response [CR] rates, are significantly higher. Data from our center that we published look relatively identical from that perspective. But…we need to improve overall survival. That is really the key primary end point of the trial, and so that is what we are currently waiting on. I think particularly for patients that can go to allogeneic stem cell transplant, the therapy is very effective. I think it really does induce deeper and what I would call [minimal residual disease (MRD)]-negative remissions, which not has not really been a thing in myelodysplastic syndrome. But I think that the balance of what percentage of patients get there may tip whether or not the trial is positive or not. Although, I think the utilization, at least in the United States, will still be significantly high. They kind of went over those data in detail. Again, we need that trial.

The 1 other main study that we hope to have data by the end of the year is the SELECT-MDS-1 [NCT04797780], which is a phase 3 trial of azacitidine/tamibarotene vs azacitidine alone. This is a little bit for a biomarker-specific group. You have to have what is called RARA overexpression, which is about 50% of MDS patients. What we are going to know at least by the end of the year is the CR rate in the first 190 patients. The trial is actively occurring up to over 500 patients with a secondary end point of overall survival. Hopefully, we are going to have both of these data, maybe by the end of the year, and maybe finally, changing that frontline landscape because the whole field is a little bit in a lull, I would say, with a lot of negative trials, and then whether or not the standard-of-care is changing or is not changing, or do we need to start from scratch and completely redesign these type of studies.

David Sallman, MD, discusses some of the innovative therapies and strategies being investigated in myelodysplastic syndromes studies.

Ansell’s Key Takeaways on Advanced Hodgkin Lymphoma From SOHO 2024

Stephen M. Ansell, MD, PhD, chair of the Division of Hematology at Mayo Clinic in Rochester, Minnesota, discusses the key takeaways from his session at 

2024 Society of Hematologic Oncology (SOHO) Annual Meeting

 in the advanced stage Hodgkin lymphoma space.

Here, Ansell highlights additional discussions from the meeting that are of particular interest to a community oncologist, including how to incorporate immunotherapies in the treatment of patients with lymphomas.

The key takeaways are that this is a field that is moving fast. I think within the US, there is a greater kind of embracing of the nivolumab [Opdivo] and AVD [doxorubicin, vinblastine, and dacarbazine] chemotherapy regimen. I certainly would say that it has advantages, because one can use it in almost any population with good results. Comparisons of in the [younger] patients and comparisons in the [older] patients, compared with brentuximab and AVD shows benefit for the nivolumab and AVD. I think a takeaway for a community oncologist is that this is probably going to become the standard of care.

Speaking of community oncologists, there [were] a number of discussions [at the SOHO 2024 Annual Meeting] about how to integrate immunotherapies, not so much now in Hodgkin lymphoma, but in other lymphomas like low-grade lymphomas and large cell lymphoma, particularly bringing bispecific antibodies to the community. Those are agents that are highly effective, but with some toxicity in the first month. How to use that in a community setting in a safe and effective way is one of the things being discussed. I certainly think it is one of those things that we will get it worked out, and it will be usable and useful across the board.

Ansell SM. Advanced Stage Hodgkin Lymphoma, the End of ABVD and BEACOPP? Presented at: 2024 SOHO Annual Meeting; September 4-7, 2024; Houston, Texas.

Stephen M. Ansell, MD, PhD, discusses the key takeaways from his session at 2024 Society of Hematologic Oncology Annual Meeting in the advanced stage Hodgkin lymphoma space.


Mauro on the Future of CML Treatment

Michael J. Mauro, MD, director of the chronic myeloid leukemia (CML) program in the leukemia service at Memorial Sloan Kettering Cancer Center, provides a summary of a presentation at the 2024 Society of Hematologic Oncology (SOHO) Annual Meeting on the recent advancements in CML treatment and applying clinical evidence to cases that are advanced.


Mauro highlights the increasing availability of effective tyrosine kinase inhibitors (TKIs) and the ongoing need for research to optimize treatment strategies. According to Mauro, one of the main goals in the CML space is to identify therapies that can lead to more patients achieving a cure or long-term remission.

 At SOHO 2024, I am part of a satellite symposium with my colleagues, Elias Jabbour, MD, and Jorge Cortes, MD. I believe the overarching theme is challenging cases in CML. I think it is appropriate now [as] in 2024, we are likely to see new frontline approvals. We have a full pallet of CML TKIs approved. We have some changes from branded drug to generic drug availability, and we have a continuing agenda to look at long term safety, optimum response, treatment, cessation. Many questions still, [and] even though we have a great list of therapies for CML, we still have work to do, especially for our patients. So, we are going to talk about an overview of the newer drugs and the developments that we have seen, and then go through cases to hopefully illustrate some of the progress we have made.

 With newer drugs showing better efficacy in the frontline, I think the holy grail in CML will be, do they bring more patients to a cure? That would be the most exciting thing for me, because I am focused on, again, high yield, low-risk therapy. I think some really offer that option, and if we then can see that with better responses and tolerability in the frontline, that converts to more patients reaching a potential treatment-free remission opportunity, or a more successful treatment for remission endeavor, that would be fantastic. That would be the icing and the sprinkles and the cherry on top of the cake.

Michael J. Mauro, MD, provides a summary of a presentation at the 2024 Society of Hematologic Oncology Annual Meeting on the recent advancements in CML treatment and applying clinical evidence to cases that are advanced. 


Targeting B-Cell Lymphomas With T-Cell Therapies

Sonali M. Smith, MD, chief of the section of hematology/oncology at the University of Chicago, discusses how T-cell–directed therapies work in the context of indolent B-cell lymphoma.

Sonali M. Smith, MD, discusses how T-cell–directed therapies work in the context of indolent B-cell lymphoma.


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