Transcription:
Leonard List 2022

Dr. John Leonard: Welcome to Weill Cornell Medicine CancerCast, conversations about new developments in medicine, cancer care, and research. I'm your host, Dr. John Leonard. And today, we'll be talking about the 15 most interesting lymphoma abstracts to be presented at the 2022 Annual Meeting of the American Society of Hematology.

The American Society of Hematology or ASH is an international meeting where the top abstracts, the top scientific and medical reports in the field of hematology, so that relates to laboratory research, outcomes research, what we call benign or non-malignant hematology, leukemia, lymphoma, myeloma, really all aspects of hematology. This also includes blood clotting, anemias, all areas of blood and the science and medicine around blood are presented. And there are a variety of different lectures. Some of these are educational lectures, scientific lectures, and then different investigators or investigator groups submit what we call abstracts, brief reports that they have been working on. And this could be the result of a study or a series of experiments. This information gets summarized and the top abstracts are selected for an oral presentation that lasts between 10 and 15 minutes. Other abstracts are selected for poster presentations where the author presents a poster about their work, and people come by and ask questions. And then, other abstracts are presented just in publication form.

And so, over the last at least five years, I have chosen prior to ASH my Leonard's List, which are areas or abstracts that I think are of particular interest And I have counted them down 10 days prior to ASH and giving a little bit of insight on what I think about these abstracts and why I think they're interesting or important. So in the 10 days prior to ASH on Twitter, I'll essentially post information each day about one of the 10 Leonard List abstracts. Occasionally, I have an A or a B around the same theme. And then for the podcast, we have added five bonus abstracts in addition to the 10 released on Twitter. And you can hear them all first here in this program. As an extra special bonus, I'm also adding a little bit of information on Abstract Number 1, which is the ASH plenary session first abstract, which is important information on mantle cell lymphoma.

So, lots packed in here. I'm going to give you some of my thoughts on key ASH abstracts. I also don't tend to pick abstracts that I was involved with, so I kind of recuse myself . And I also try to pick a few not as obvious abstracts audience to find a few little gems that people attending the meeting or going through the abstract book online might have missed. So, let's go ahead and get started.

For Leonard List number 10 for 2022 ASH, I have selected Abstract 449. This is entitled Outcome of Patients with Primary Mediastinal Large B-cell Lymphoma After R-CHOP21, R-CHOP14 and R-ACVBP: Pooled Analysis of Clinical Trials from Lysa. This is led by Dr. Sibon and colleagues. So, the Lysa Group is a large clinical trials group based in France and elsewhere in Europe, and they have conducted many important groundbreaking clinical trials over the years.

They went and analyzed a number of different trials from 2003 to 2015, five prospective clinical trials in younger patients with aggressive lymphoma. Of these trials, there were 1,177 patients included, 290 of them had primary mediastinal B-cell lymphoma. This is a subset of aggressive lymphoma, tends to present in younger women in the mediastinum or in the chest, often has a bulky mass and can be treated in a variety of different ways, often with radiation. And one of the concerns in this group of patients is the issue of radiation potentially causing long-term effects in a population of patients who tend to be younger, tend to be women where breast cancer risk is of particular concern.

And so, in this trial, there were 290 patients with primary mediastinal lymphoma, I should say this study on a variety of trials. Fifty-nine of them received R-CHOP21, a standard therapy; 70 received R-CHOP14 on a 14-day treatment cycle rather than 21; and then, 161 received R-ACVBP, which is a more aggressive regimen that is sometimes used in France.

so these patients were not randomized between these arms, but when you look at the primary mediastinal lymphoma patients treated on these studies, the takeaway point is that R-CHOP14 and R-ACVBP improved progression-free and overall survival compared to R-CHOP21, and there was more toxicity with R-ACVBP. And so, the authors conclude that R-CHOP14 may be a preferred regimen for young patients with primary mediastinal lymphoma. So interesting data. Some parts of the world, R-CHOP21 has been the standard. This suggests that R-CHOP14 might be better. And I'll just highlight that there are many people in the world who use the dose-adjusted R-EPOCH regimen for this group of patients. And in fact, there is an important national study going on in the US using R-CHOP or R-EPOCH with or without an immune checkpoint inhibitor, nivolumab, that is going on nationally and that's a particularly exciting trial for those of you who are involved in patients with primary mediastinal lymphoma.

So next, we'll move to Leonard List number nine for ASH 2022. This is Abstract 2863, entitled Alterations of Immune Cells by Large B-Cell Lymphoma Persist Years After Achieving Complete Remission and Correlate with Impaired Adaptive Immunity. This is from Dr. Pelzl and colleagues, from Nurnberg, Germany.

So, this is an interesting study, I thought particularly timely given all the concerns we have about immune deficiencies in patients with lymphoma, particularly in the times of COVID. And these authors looked at and are focused on cells that occur in a tumor microenvironment called myeloid derived suppressor cells or MDSCs. These are myeloid or early white blood cells that essentially modulate the immune response within tumors and can also be seen in the blood.

And so what these authors did they looked at blood samples to look at the immune status of patients newly diagnosed with diffuse large B-cell lymphoma, patients who had diffused large B-cell lymphoma and are cured and are years later, and then healthy donors. And what they found was that these MDSCs that are seen in patients with lymphoma and can suppress the immune response; in some ways, persist and in some cases, can persist for years later. And in fact, this persistence seems to be associated with the antibody response to COVID vaccination and also can be associated with effects on T-cells in patients against the COVID virus or SARS-CoV-2.

And so, the takeaway from this, and this is a small study, it's not definitive, but we tend to think of patients with lymphoma having an impaired immune response or an impaired immune system at some level. This gives some objective data to suggest that just having lymphoma, whether it's the lymphoma itself or the fact that lymphoma could happen in such patients, that patients with lymphoma untreated have an immunocompromised state and, more importantly and interestingly, patients who had an aggressive lymphoma years later, two years later, can still have an impaired immune response and that this might be potentially relevant even for infections such SARS-CoV-2. So, not a definitive study, but I think very interesting data and hopefully will lead to more work.

Next for Leonard List ASH 2022, number eight is Abstract Number 730, Brentuximab Vedotin Combined with Chemotherapy in Newly Diagnosed, Early-Stage, Unfavorable-Risk Hodgkin Lymphoma: Extended Followup with Evaluation of Baseline Tumor Volume and PET2. This is from Dr. Stuver and colleagues and a multi-center group including Memorial Sloan Kettering. So, this is an analysis of patients treated on a clinical trial in early-stage Hodgkin lymphoma. The treatment regimen here was brentuximab vedotin plus AVD chemotherapy. And the bottom line is that outcomes were generally good for this population of patients. This regimen has been presented before.

The interesting part of these 117 patients is that there was a sophisticated analysis looking at metabolic tumor volume, basically a quantitative analysis of uptake on the baseline PET scans. And the idea here is trying to use metabolic tumor volume in addition to PET scan results after two cycles of therapy to predict outcome. And so, metabolic tumor volume was defined as either low or high. The median was the cutoff. So, half the patients had low, half had high.

And the takeaway here was that the combination of high metabolic tumor volume at baseline before therapy and a positive PET scan after two cycles of therapy correlated with a less favorable outcome. However, patients who had one or the other or neither of metabolic tumor volume being high and a positive PET scan, so if you only had one of those factors or none of those factors, you did well in this particular study. Now, this is a small study. There were under 40 patients in each of these groups, but it really calls attention to the fact that metabolic tumor volume is a potentially important factor in predicting outcomes when measured at baseline for patients with Hodgkin lymphoma. And the idea here is that the combination or some combination of metabolic tumor volume pre-therapy and PET2 uptake. After two cycles of therapy, that this combination might be particularly useful in risk-adapting therapy for patients with Hodgkin lymphoma as we try to essentially tailor therapy up or down based on an individual patient's risk profile.

Next, we'll move to Leonard List ASH 2022, number seven, and in fact for this one I have a seven A and a seven B around the same theme. The first is seven A, Abstract 2267, Disparities in Outcomes of Diffuse Large B-cell Lymphoma in Adolescent and Young Adults: A SEER Database Analysis. This looks at patients falling in the adolescent and young adult patient population age 15 to 39 and diffuse large B-cell lymphoma, which is the second most common lymphoid cancer in this AYA age group.

This study evaluated racial disparities in outcome. It was a large study from the SEER Registry looking at over 9,000 patients with diffuse large B-cell lymphoma falling into the AYA population from 2000 to 2019. There was a large group of distributions of age, race and gender. And the takeaway here is that black patients were more likely to be men, tended to be part of low-income groups, tended to have advanced stage disease, although this part was not statistically significant, interestingly were less likely to receive chemotherapy and, in fact, had an inferior overall survival at five years that was 66% versus 80%. So again, the difference in survival between black patients and other races was significant despite adjusting for a variety of different factors in adolescent and young adult patients with diffuse large B-cell lymphoma. So, something that we need to investigate and address further.

On the other hand, selection seven B, Abstract 2902 looks at Current Status of Racial and Ethnic Disparities in Follicular Lymphoma: A SEER Database Analysis with an Emphasis on Hispanics. So, a different type of lymphoma, different focus here. This is from Rosas and colleagues, primarily from San Antonio.

And this study essentially looked at patients with follicular lymphoma databases from 2000 to 2018 and looked at a variety of different factors almost 60,000 patients with follicular lymphoma. Eleven percent of these patients were Hispanic. The Hispanic patients were diagnosed at a median younger age compared to the non-Hispanic patients. And interestingly, they tended to have similar other characteristics. But importantly, the median survival time was better in patients that were Hispanic versus non-Hispanic. The overall survival was improved in patients with follicular lymphoma who were of Hispanic background.

And so, this is quite provocative. There were differences at two, five, and 10 years in this cohort. And the questions really raised the issue of what are the unique characteristics in these individuals that were associated with a better outcome, at least in this very, very large cohort of patients. So, interesting data focused on different outcomes and disparities in patients with certain subtypes of lymphoma, in this case, AYA and follicular lymphoma.

Next for Leonard List ASH 2022, selection number six, we have Abstract 955, Sintilimab plus P-Gemox Regimen for Newly-Diagnosed Advanced, Extranodal NK/T-cell Lymphoma: A Multicenter Phase II Cohort. So, extranodal natural killer T-cell lymphoma or ENKTL, is an aggressive subtype of lymphoma, more common in Asian and South American populations. And historically, the prognosis has been quite poor. There are several agents including pegasparaginase, oxaliplatin, gemcitabine, commonly used for patients with this subtype of lymphoma. Interestingly, the patients with this subtype of lymphoma tend to over express the PDL-1 protein. This is associated with a less favorable outcome, but suggest that immune checkpoint inhibitors may be particularly relevant for this subpopulation of patients given the presence of this target.

And so, this study took earlier work using the PD-1 monoclonal antibody sintilimab, that showed some activity as a single agent in patients with recurrent extranodal NK/T-cell lymphoma, and essentially evaluated a new regimen using sintilimab plus P-Gemox, which includes pegasparaginase, gemcitabine and oxaliplatin. So, this was a study of 22 patients. Median age was 38, and a fair number of them had high risk features. There were 24 patients evaluable for response. And again, the issue there is that almost all of them were evaluable for response. The response rate was 100%. The CR rate was 87%. And the median overall survival and progression-free survival were not reached. These were estimated at one year to be between 95% and 100%. And the toxicity here due to these agents was substantial. But in the context of a very challenging subtype of lymphoma to have such a high complete response rate and a fairly promising one-year progression-free and overall survival suggests that this is a regimen that warrants further study and is being studied further, but is certainly quite encouraging for a challenging subtype of lymphoma.

Now, for Leonard List ASH 2022, number five, we're going to again have a five A and five B. And first five A is Abstract 798, Incidence of Second Primary Malignancies in Lymphoma Survivors: A Prospective Cohort Study in the Modern Treatment Era. This is from Dr. Desai and colleagues from the University of Minnesota and from the Mayo and Iowa collaboration through their Molecular Epidemiology Resource, which has been a major contributing resource to lymphoma knowledge. And the University of Iowa Mayo Clinic SPORE has been a frequent mention on the Leonard List over the years because of contributions like this.

So, this looked at patients with lymphoma who were entered on this prospective database. And with very rigorous followup, this database has close to 7,000 patients and looked over time at this group of patients as to second primary malignancies. And of these 7,000 patients, about 763 developed a second primary malignancy. Thirty-seven of these were acute myeloid leukemia and myelodysplastic syndrome. Three-hundred forty-one or almost half of the second primaries were non-melanoma skin cancer. There were 133 cases of GU cancers, genitourinary cancers; 57 GI cancers and 49 breast and 52 lung cancers. So overall, the 10-year cumulative incidence of second primary malignancies was 12%. That being said, this was substantially lower, than death as a competing risk. So, clearly, the overall outcomes for most patients were not affected by the second primary lesions. And given the fact that about half of these were due to non-melanoma skin cancers, it highlights that dermatology or other screening for skin cancers is important in this population. And otherwise, the risk of secondary AML or myelodysplasia was low, although still fivefold higher than the expected population risk. And so, I think this just highlights the fact that we need to watch our lymphoma patients for second primaries, make sure they're being monitored and screened for these late events.

Five B is Abstract 448 focused on Reproductive Patterns Among Non-Hodgkin Lymphoma Survivors By Subtype in Sweden, Denmark and Norway. This was a cohort study, a matched cohort study that looked at patients treated for various forms of non-Hodgkin lymphoma.

There were over 2000 patients included and 20,000 comparators. They chose patients of the appropriate age range to look at and they looked at patients with both indolent and aggressive lymphoma. The takeaway here is that reproductive patterns among survivors with indolent lymphoma were quite similar to their comparators within the first three years after diagnosis among both males and females. This may reflect the nature of therapy or perhaps a lack of therapy for some of these in indolent lymphoma patients.

On the other hand, reproductive rates and patterns in patients with aggressive lymphomas were lower in the first three years and then were raised after the three-year period to be closer to those of their comparator group, again probably because of the nature of therapy that these patients were receiving during this time and the desire to wait a bit to ensure that the lymphoma was under control in this curative lymphoma setting. So, I think these are other important data highlighting the value of fertility counseling and discussion of fertility with these patient groups who are of childbearing age and interest.

Next Leonard List selection number four, 4898, Utilization of Palliative Care in Diffuse Large B-Cell Lymphoma Patients is Linked to Insurance Type and Household Income. This is from Dr. Abodunrin and colleagues from Omaha, Nebraska, Creighton University and other collaborators. This is focused on the importance and need of palliative care in patients with solid and hematologic malignancies.

These investigators looked at the National Cancer Database, identified 264,000 patients, and these were all patients with diffuse large B-cell lymphoma. And they found that only 3.2% of these patients ever utilized palliative care. This has increased in recent years, but still a small proportion of patients with a diagnosis of diffuse large B-cell lymphoma ever received palliative care. This was more common in older patients, less common in younger patients, also less common in privately-insured patients interestingly. And patients with higher incomes were less likely to receive palliative care. So, some interesting associations there.

They speculate that low levels of palliative care were seen in privately-insured patients and higher income patients, perhaps because the coverage of palliative care, perhaps because patients with private insurance and at higher income levels were more likely to pursue novel therapy. So, perhaps some interesting insights into disparities in part and also highlights the fact that we need to consider palliative care in patients with diffuse large B-cell lymphoma because, unfortunately, a substantial number of these patients still can benefit from palliative care regardless of their prognosis, and very few patients are receiving palliative care in this setting.

Next Leonard List ASH 2022 selection number three, Abstract 549, Viral Cell-free DNA Profiling reveals distinct EBV subtypes and stratifies risk in non-Hodgkin Lymphoma. This is from Garofalo and colleagues at Stanford and elsewhere.

And this study, I think, is interesting and thought-provoking, highlights the idea that patients with Hodgkin lymphoma, a subset of these patients have tumors that are Epstein-Barr virus positive, and also can be associated with immunodeficiency. There's some evidence that these viral infections can be important at some level in the pathogenesis of classical Hodgkin lymphoma. And so, the net of this study, 352 patients with classical Hodgkin lymphoma. There were about half of the patients that had detectable Epstein-Barr virus cell-free DNA above the background level. And interestingly, these levels were higher in patients with classical Hodgkin lymphoma disease and were EBER positive or Epstein-Barr encoded small RNA positive tumors. And these authors went on to start to evaluate clustering of 180 targeted viral species within the EBV spectrum and had some evidence to suggest that the EBV profile, had some correlation with outcome.

And so, this is an interesting finding, early analysis, early data, but suggest that the role of EBV in Hodgkin lymphoma could potentially be more important than we have traditionally thought. And in fact, by better characterizing EBV infection in these patients, this may be something that enables us to risk stratify patients and potentially change therapy.

For Leonard List number two for ASH 2022, we're going to move to Abstract 1649 by Cox and colleagues from Rome, Italy, entitled Remarkable Remission Rate and Long-term Efficacy of Upfront Metronomic Chemotherapy in Elderly and Frail Patients with Diffuse Large B-cell Lymphoma. So, this is a retrospective study from four centers using a metronomic or low-dose intermittent-day chemotherapy schedule.

This is something I've been interested in earlier in my career. We used the PEP-C regimen, very commonly an oral regimen as a palliative regimen. These investigators looked at the R-DEVEC regimen, looking at oral cyclophosphamide, Vinorelbine, etoposide and prednisolone given orally on a metronomic type of schedule, an alternate day or a skip-day schedule along with rituximab. These were very elderly, very frail patients, and median age of 85, given this regimen as an upfront approach. And you would expect that outcomes would be quite challenging. Interestingly, with a median followup of 22 months, 15 of these patients had died, although about half of those died from causes unrelated to B-cell lymphoma and treatment. But interestingly, two-thirds of the patients achieved a complete remission and the overall and progression-free survival at 24 months was 56% and 70% respectively.

And so, these are interesting data that suggests that this non-sexy oral chemotherapy approach can still have a meaningful outcome with patients who are quite elderly and frail as an initial therapy with diffuse large B-cell lymphoma. So, sometimes there are oldies but goodies that can be helpful to our patients and, obviously, add value in certain clinical settings, particularly when you're focused more on palliation.

For Leonard List number one, ASH 2022, I've selected Abstract 763. This is from Dr. Barta and colleagues, entitled Observational Cohort Study of People Living with HIV Treated with CD19-directed CAR T-cell therapy for B-cell Lymphoid Malignancies - Interim Results of AIDS Malignancy Consortium Study, AMC-113. So, this is a trial. That is a prospectively-collected registry study using CIBMTR data for patients diagnosed with HIV who had lymphoma or other B-cell malignancies who have received CD19-directed CAR T-cell therapy. Interesting and important population and data.

This reports on 21 patients from 13 centers, median age of 55. And these patients had either follicular lymphoma, mantle cell lymphoma, or much more commonly large B-cell lymphoma. Several had had a prior auto transplant. Median time from HIV diagnosis was almost 10 years. And the median pre-CAR-T CD4 count was about 228. And most of these patients who had an analysis had relatively low HIV viral loads. And the data on these patients was that overall survival, it's a short follow up, median followup of six months, but overall survival was 83% at three months and 64% at six months. Several of those who died died of disease progression. But the important part of this is that some of these patients did well admittedly with short followup.

And so, this is the largest series of patients with HIV who have been treated with CAR T-cell. It also includes a large number, about half the patients were from underrepresented populations, important. And essentially, the authors conclude that this approach was safe and efficacious in this patient population and similar to data from patients without HIV. So, this study's ongoing and I think it's important data for this population of patients who continues to have need for new and appropriate therapies for their lymphoma in the context of living with HIV.

So now, I'm going to move to bonus abstracts very, very briefly. A few bonus abstracts for those of you listening to the podcast that we're not covering on Twitter. First, bonus number one, Abstract 4214, Characteristics of Patients with Observation As Initial Treatment Strategy in Mantle Cell Lymphoma. My colleague, Peter Martin, led a study over 10 years ago where we established that watch and wait or observation was a reasonable treatment strategy for some patients with mantle cell lymphoma. These are data from the Flatiron Health Electronic Record Database looking at over 4,000 patient, 3000 of which approximately met inclusion criteria and there were 800 patients with mantle cell who made up the observation group. So, this is a very large cohort of patients with observation.

Interestingly, of those who went on observation, a third of them had not had any documented treatment. The median followup duration was about five years or so. And interestingly, the median time to treatment initiation was over a year for the observation group. So, the net is that outcomes were similar. These tended to be patients with more favorable disease, but essentially about a quarter of patients in a population-based sample were not treated immediately. And the median time to diagnosis to treatment of this group was just over a year. And so again, further supports that observation is a reasonable strategy in selected patients with mantle cell lymphoma.

Bonus selection number two, Abstract 2907, Administration of Obinituzumab, and Not Rituximab, During Induction and Maintenance for Follicular Lymphoma Increases the Likelihood of Developing Delayed Neutropenia. This is a retrospective study from the Rambam Medical Center in Israel, led by Dr. Harlev. This was a retrospective analysis looking at the electronic medical records of patients with follicular lymphoma. They looked at just over 300 patients with high-tumor-burden follicular lymphoma, analyzed the treatments, analyzed those patients who received maintenance, about 150 patients received maintenance. And interestingly, 23.6% of patients on maintenance develop delayed neutropenia. This was enriched for patients who had received bendamustine and enriched for patients who received obinituzumab/bendamustine as their initial therapy.

So, this highlights in particular that obinituzumab with bendamustine can be associated with delayed neutropenia. And importantly, in this group of patients, 40% of those who had delayed neutropenia were hospitalized with neutropenic fever. And so while this has generally been felt to be a benign complication, the fact that 40% of patients with delayed neutropenia required hospitalization adds to its clinical significance. So, keep that in mind as you choose to use maintenance and which agent you choose in follicular lymphoma.

Next, bonus number three, Abstract 792, Prediction of Poor Outcome After Tisagenlecleucel in Patients with Relapsed or Refractory Diffuse Large B-cell Lymphoma Using Artificial Intelligence Analysis of Pre-infusion PET-CT. So, this is from Jak and colleagues from Utrecht in the Netherlands. This looked at patients in the pivotal JULIET study using tisagenlecleucel in relapsed or refractory diffuse large B-cell lymphoma and looked at metabolic tumor volume that we alluded to earlier, showing that high metabolic tumor volume also predicted early relapse. They went on to try to identify a subgroup of patients at very high risk of a poor outcome, either death or disease progression, by looking at the PET scans, the pre-infusion FDG PET/CT, along with clinical and pathological parameters.

The takeaway from this is that these authors were able to identify an artificial intelligence signature that could identify a hundred percent of patients with a poor outcome. And so again, this is retrospectively developed. It needs to be prospectively studied and it's a limited number of patients overall, 115 data sets from patients using their FDG PET, but suggests that using artificial intelligence and the pre-therapy PET characteristics, one might be able to identify a signature that suggests a much less favorable outcome, and then would lead to a different therapy potentially. Very early data, but interesting and something to keep an eye on regarding the potential for artificial intelligence in the future as we analyze therapies in lymphoma.

Next, we'll move to the fourth bonus selection, Abstract 4198, Results from a Phase I/II Study of Tandem, Bispecific Anti-CD20/Anti-CD19 CAR T-Cells for Mantle Cell Lymphoma. This is from Dr. Shah and colleagues of the Medical College of Wisconsin. This was a phase I/II single center prospective trial looking at CAR T-cell that target both CD20 and CD19, along with a 4-1BB co-stimulatory signaling molecule, looking at patients specifically in mantle cell lymphoma in this analysis. This looked at a group of patients with mantle cell lymphoma, 10 patients, so obviously a small group of patients, relatively short followup. But with this analysis, there were no relapses out of these 10 patients with an overall response rate of a hundred percent, median followup of over one and a half years, no grade 3 or 4 cytokine release syndrome, and very low rates of grade 3 or 4 ICAN. And these were all manufactured on site using an eight-day platform So interesting data, small study, short followup, but very high, a hundred percent overall response rate. Need more patients and more studies, but encouraging in patients with mantle cell lymphoma, a novel CAR T-cell agent.

And then, bonus number five is the Abstract 735 at ASH 2022, Five-Year Survival Results from the Remodl-B Study Show Improved Outcomes in Diffuse Large B-cell Lymphoma Molecular Subgroups from the Addition of Bortezomib to R-CHOP Chemoimmunotherapy. We have been interested in, others have been interested in, including the Remodl-B group of investigators, led by Dr. Davies and colleagues from the UK. The Remodl-B study compared R-CHOP versus R-CHOP plus bortezomib in patients with diffuse large B-cell lymphoma, stratified by cell of origin using gene expression profiling. The initial results from this analysis were negative, did not show a benefit of bortezomib. This report now is a retrospective analysis using expression-based classifier.

So, the takeaway of this study is that, while the Remodl-B study showed no difference in the gene expression profiling cohorts, we now see that in this retrospectively identified subgroup of patients using this molecular high-grade classifier, a potential difference in the effectiveness of bortezomib R-CHOP versus R-CHOP alone. Interesting data, not yet ready for prime time, but hopefully will be studied further and perhaps a little bit more life in the molecular classification of large cell lymphoma for selection of targeted therapy approach that has been active for many years, but quite limited in its benefit to patients thus far.

And finally, I wanted to end with just a few words on my thoughts on Abstract Number 1 from ASH 2022. This is the plenary session presentation from Dr. Dreyling and colleagues, the Efficacy and Safety of Ibrutinib Combined with Standard First-Line Therapy or as a Substitute for Auto Stem Cell Transplant in Younger Patients with Mantle Cell Lymphoma: Results from the Randomized Triangle Trial by the European Mantle Cell Lymphoma Network. So, there's been a lot of discussion over the years as to the role of auto transplant in first remission for patients with mantle cell lymph. Many have advocated that it is a standard of care or the standard of care for younger patients based on progression-free survival benefit, but less convincing, if at all, overall survival benefit.

So, the triangle study looked at what was deemed the standard of care, R-CHOP/R-DHAP followed by auto transplant versus the same regimen including an auto transplant plus ibrutinib versus R-CHOP/R-DHAP with ibrutinib, so no auto transplant. And the net of this study suggests that the addition of ibrutinib during induction and in maintenance with or without auto transplant showed a strong effectiveness with acceptable toxicity, these were the choices of the authors, but basically was not superior to the auto transplant-containing arm. So that at least in the presence of ibrutinib, an auto transplant is not needed to achieve the same progression-free survival and overall survival.

So, I think these are important data, calling into question the value of auto transplant, which some of us question to begin with in mantle cell lymphoma and now suggesting that certainly, with ibrutinib, you don't need to perform an auto transplant in patients with mantle cell lymphoma in first remission. And I think these are interesting and important data. I'll remind you that there is an ongoing intergroup US study looking at auto transplant in patients in complete remission MRD-negative after their induction therapy with mantle cell lymphoma. So, I think there's still some discussion as to the role of auto transplant and mantle cell lymphoma. But as we and some others have argued for the value of auto transplant and mantle cell lymphoma, I think is less convincing and, after ASH 2022, probably will have a much more limited role, if any, in the treatment of even younger patients frontline receiving therapy for mantle cell lymphoma.

So that concludes our discussion of the Leonard List ASH 2022 selections. I hope you've enjoyed hearing our 10 abstracts that were chosen. You'll see them more on Twitter and have links to them, as well as the bonus take on five additional abstracts and Abstract Number 1. I would say that there are lots of great data being presented at ASH 2022. There's more than what I was able to cover in this group, but I think some of this information clearly is impacting patients, clearly is impacting the field. It highlights the fact that we need to comor support research, continue to contribute to and conduct clinical trials and other observational studies. And I would encourage the audience to take even a closer look at what's happening at ASH. I look forward to my tweets at the meeting and other venues including ASH updates where we can get even more detail into what's new from ASH and how this is both moving the field forward and impacting patients with lymphoma.

So, thank you for listening to this episode. I've enjoyed putting it together. I want to invite our audience to download, subscribe, rate, and review CancerCast on Apple podcasts, Google Podcasts, Spotify or online at weillcornell.org. We also encourage you to write to us at cancercast@med.cornell.edu with questions, comments, and topics you'd like to see us cover more in depth in the future.

That's it for CancerCast, conversations about new developments in medicine, cancer care, and research. I'm Dr. John Leonard. Thanks for tuning in.

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