Understanding the Research on Novel Treatments and Nutritional Interventions for Multiple Myeloma With Urvi Shah, MD
During the recent American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Dr. Urvi Shah from Memorial Sloan Kettering Cancer Center sat down with Oncology Data Advisor to share her perspectives on the exciting research that was presented in the poster discussion session she chaired on novel therapies for multiple myeloma. In addition, Dr. Shah explains more about her work to impact patients' quality of life and outcomes through nutritional interventions.
This podcast episode was recorded live at the 2022 ASCO Annual Meeting in Chicago by Oncology Data Advisor and ConveyMed.
Oncology Data Advisor: Welcome to Oncology Data Advisor, I'm Keira Smith. Today, I'm here at the ASCO Annual Meeting in Chicago, speaking with Urvi Shah from Memorial Sloan Kettering Cancer Center (MSKCC). Thank you for joining us. Would you like to tell us a little bit about yourself?
Urvi Shah, MD: Sure. I'm a Hematologist and Oncologist on the Myeloma Service at Memorial Sloan Kettering Cancer Center. I'm happy to be here to talk to you all.
Oncology Data: I know you moderated the poster discussion session yesterday about plasma cell dyscrasias. Would you like to tell us a little bit about the posters that were presented there?
Dr. Shah: Definitely. I think the session was really well attended. It was a fantastic session in terms of the science presented. We had four panel discussants who discussed 11 abstracts. The topics that we discussed were CD38 monoclonal antibodies, bispecific antibodies, CAR T cells, and the correlative analysis around them. We also discussed antibody-drug conjugates, including the DREAM studies. I'll go over each of them briefly.
The first is CD38 monoclonal antibodies; we know they've been FDA approved since 2015. Dr. Weisel put it into perspective with the two abstracts that we were discussing. One of the two abstracts was by Dr. Cesar Rodriguez on the GRIFFIN study. GRIFFIN is basically a study looking at daratumumab (dara)-VRd (bortezomib/lenalidomide/dexamethasone) compared with VRd in the upfront newly diagnosed myeloma setting. What he showed was that the dara-VRd arm, which is a quadruplet, had improved progression-free survival (PFS) and minimal residual disease (MRD) negativity, as well, compared with the VRd arm.
We know that this combination does lead to longer and more sustained responses; however, they showed data on a subgroup analysis of high-risk myeloma. That significance didn't exactly correlate into that population, but that's probably because of the small sample size. I think we need more data in the long term to really understand what the significance would be. But if it's benefiting the standard-risk patients, it might be benefiting the high-risk too, in some ways, compared with the triplet.
The next abstract Dr. Weisel talked about was the abstract by Dr. Andrew Yee about using the CD38 monoclonal antibody, daratumumab, again, but this was a quadruplet in the relapsed myeloma setting. This is daratumumab, carfilzomib, pomalidomide, and dexamethasone all used together. In this study, there were about 54% of patients who were standard risk, so it wasn't all high-risk patients. They didn't talk about how many of them were functionally high-risk or what their PFS1 was, but what we do see is that patients had really nice PFS2 and remission times with this combination.
However, I think questions remain in terms of, if you are doing a quadruplet at relapse and you're continuing all four drugs until progression, are we overtreating some patients or are we maybe curing some patients? I think time will tell. The other question that came up was that if you're doing a quadruplet with daratumumab in the relapse setting, what about the patients who get it in the upfront setting? Does it still matter to add it in the relapse setting? I think, as things are moving so quickly, even the relapse setting needs to change.
The next discussant was Dr. Cristina Gasparetto, who talked about the antibody-drug conjugates and "finding your DREAMM partner," so she discussed all the DREAMM studies. The three studies and abstracts that were discussed were DREAMM-4, -5, and -6. DREAMM-4 is a study looking at belantamab mafodotin with pembrolizumab. This was a poster presented by Dr. Suvannasankha; however, pembrolizumab with belantamab did not show any improvement in overall response rate and did not show any difference in toxicity. The study was a negative study, but it is nice to highlight these kinds of studies too, so we understand what's working and not.
The next study was the DREAMM-5 study, which was the poster presented by Dr. Lonial, looking a gamma-secretase inhibitor (GSI) along with belantamab mafodotin. This GSI increases the expression of the BCMA target, which belantamab targets. What the study did show is that there was an improvement, about similar response rates, but a reduction in toxicity. It was ophthalmologic toxicity. This drug tends to cause high toxicity, and about 70% in the original studies had high toxicity. With this combination, because it increases the expression of the target, we were able to lower the dose of the drug needed. Since the drug dose was lower, the eye toxicity was reduced, but the response rate was maintained. That's actually a way to keep the responses but mitigate the toxicity issues. So that seems promising, and I think we'll see more of that going forward.
Then the DREAMM-6 study looked at lenalidomide with belantamab mafodotin. However, this was in the earlier setting, so one, two, or three prior lines. In this setting, there were about 50% of patients who had not received lenalidomide before. While the responses looked very good, it's hard to know if it's fully the belantamab effect or if part of it is the lenalidomide effect. This combination could be promising too. We did discuss in the panel that lenalidomide is already used upfront for most patients. By the time belantamab is used in the relapse setting, most patients might be refractory to it. We need to look at other DREAMM partners, like maybe pomalidomide or iberdomide, instead of just lenalidomide. I think those may be things we'll see down the road.
The next two discussions: Dr. Robert Mina discussed four abstracts on bispecific antibodies. He discussed abstracts looking at teclistamab, talquetamab, and elranatamab. What he showed is that teclistimab, which was presented by Dr. van de Donk as a poster comparing teclistimab to real-world data, showed a significant survival benefit compared with standard of care options in the LocoMMotion study. This is something we would kind of expect with a new drug and target that's being used. But it's exciting because teclistamab is a drug that we might soon see available to patients, because its data is maturing and nearing approval.
Next, the same drug, teclistamab, was looked at in another abstract where they looked at, what if we sequence BCMA therapies one after the other? Do patients still respond if they already had a BCMA therapy upfront? All patients in this cohort had received prior BCMA therapies. What they showed is, despite receiving prior BCMA therapies, the patients had about a 50% or so response rate. I think that's promising, that despite them having already received one of these therapies, they still responded to the next one.
The third one was on talquetamab, which is a different target, a GPRC5D target. They looked at different dosing schedules and showed that they are similar, so once weekly versus once biweekly. But overall, their response rates with all of these bispecifics are about 60% to 70%. They're overall well tolerated except for the increased risk of infections, which need to be managed and monitored for. Dr. Chiari did bring up an important point that with talquetamab, we see less of the hypogammaglobulinemia than we see with BCMA-targeting agents. One more was the elranatamab abstract by Dr. Jakubowiak, who had presented that poster, showing that elranatamab in the MagnetisMM-1 study had about a similar response rate of 70%. They also had a cohort of patients that had prior BCMA therapies and saw similar results of about 50% response rates. I think it's nice that two studies are showing the same thing.
The last abstract discussion was Dr. Alfred Garfall from the University of Pennsylvania. He discussed two abstracts, one discussing idecabtagene vicleucel (ide-cel) and the other ciltacabtagene autoleucel (cilta-cel) and the correlative analysis around it. The cilta-cel study was the CARTITUDE-2 study looking at patients with one to three prior lines of therapy. This is different than the CARTITUDE-1 study, which looked at more heavily relapsed patients. What they did show is that patients with one to three prior lines also had very good similar responses to the CARTITUDE-1 study, but their responses were so good in CARTITUDE-1 that it was hard to show a significant improvement despite this being in earlier lines of therapy. I think, overall, we can say that this is a promising therapy. What was interesting is that they looked at other correlatives and set a better CD4/CD8 ratio, and interleukin-6 (IL-6) levels tend to correlate with CRS or cytokine release syndrome. There is a little bit of a signal on what tends to increase the risk of these side effects.
The last poster that was discussed was the poster looking at ide-cel. They looked at baseline characteristics, both patient factors and the manufacturing characteristics, and clustered these different characteristics into four different clusters: Clusters 1, 2, 3, 4. Cluster 4 was the best, and Cluster 1 was the worst in terms of outcomes. They showed a different PFS benefit with each of these clusters. Looking at these clusters, we know that factors such as the albumin level, absolute lymphocyte count, or CD4/CD8 ratio are important in knowing whether a patient might benefit.
I think these studies give us pause to think that CAR T cells may not be something that is right for everybody, but we can at least figure out which are the right populations that should be getting these drugs and the ones that may not benefit but might actually have the side effects from it. While it's not directly translatable yet because there are so many different factors, Dr. Garfall mentioned an important point that maybe a validated scoring system could be included, which would help us decide—if a patient gets the right score, they may be one to benefit from these therapies.
With that, I'll conclude that I think we saw a lot of interesting data, and it was put into perspective really well with all the discussions. It was well attended too.
Oncology Data Advisor: Great, thank you. That was a fantastic overview. It really helps put all the data into perspective, so thank you.
Dr. Shah: You're welcome.
Oncology Data Advisor: I know a lot of your own research also focuses on multiple myeloma and nutrition. What are the studies that you currently have open in this space?
Dr. Shah: That's a great question. Nutrition is something we're looking at because it's the most-asked question by patients. I don't think we have much data in this space other than epidemiologic studies. We have one pilot study currently open and enrolling, that's almost nearing completion, but we still have a few spots left. This is the NUTRIVENTION pilot study. What this study is looking at is patients with monoclonal gammopathy of undetermined significance (MGUS) or smoldering myeloma and a body mass index (BMI) over 25. Patients get a whole-food, plant-based diet for three months. They're followed for one year on the study. Our primary end point on the study is weight loss, but we're also looking at other markers like the metabolic markers, myeloma markers, the microbiome, and other immune changes. We're looking forward to getting this data out by the end of the year, because we are close to finishing the study. That's the NUTRIVENTION pilot study.
The next study, the NUTRIVENTION-2 study, which I think will open closer to the end of this year, is kind of like a signal-finding study with The HealthTree Foundation. This study will be a telehealth study. It's nice because patients can be all over the country and they don't have to come to our institution at MSK. This study is going to be a 100-patient study. They're going to be only patients with smoldering myeloma, and they can have any BMI. The study has four different cohorts; one cohort will receive two weeks of probiotics, another two weeks of curcumin, another two weeks of omega-3 fatty acid, and the last cohort receives two weeks of a whole-food, plant-based diet. Patients will be randomized and we'll be collecting stool to understand changes on the microbiome. This is only a microbiome study and we're not looking at other things in this study.
The third study, the NUTRIVENTION-3 study, is a study very similar to the first one that I talked about, except it includes any-BMI patients and it's a randomized study. This study will actually be a very large study of 150 patients. It's going to open at MSK and likely at another site in Atlanta, and Emory as well, down the road. This study is going to be a randomized controlled study. There will be 50 patients receiving diet versus 50 receiving supplements, which are omega-3 and curcumin, and 50 patients receiving placebo supplements. But to make it interesting for all patients, all patients will receive the diet at some point on the study for three months. The ones that get the placebo or the supplement will just get the diet after three months. All patients will be followed for a year on this study.
Then the last study, the NUTRIVENTION-4 study, that we actually have open at MSK at this time, is in patients who are in the myeloma space. This is patients who had myeloma and they finished induction therapy plus/minus a transplant, they're going on to maintenance therapy, and they've achieved more than a very good partial response. Once they've achieved that response, they can go on this randomized study looking at quality-of-life factors between daratumumab and lenalidomide. There'll be 50 patients randomized in each arm, making it overall a 100-patient study.
What we've done is we've developed a sub-study called the NUTRIVENTION study, which is completely optional for patients that go onto the primary dara versus len study. Fifteen patients on each arm will be given the opportunity to get three months of a whole-food, plant-based diet. We're going to look at the effect of the diet in patients on maintenance therapy, as well—whether diet and the microbiome affect the immune system and immune therapies and if we can see changes around that. We're excited about these four studies, hopefully they'll all be open by the end of this year, though two are already open at this time.
Oncology Data Advisor: That's great. This is all really fascinating. It'll be exciting to see what happens with the studies.
Dr. Shah: Thank you so much.
Oncology Data Advisor: Well, thank you again for stopping by. It was wonderful to talk with you.
Dr. Shah: Likewise.
Thank you for listening to this podcast recorded live at the 2022 ASCO Annual Meeting by Oncology Data Advisor and ConveyMed. For more expert perspectives on the latest in cancer research and treatment, be sure to subscribe to the podcast at conveymed.io and oncdata.com. Don't forget to follow us on social media for news, exclusive interviews and more.
About Dr. Shah
Urvi Shah, MD, is an Assistant Attending Physician in the Myeloma Service at Memorial Sloan Kettering Cancer Center in New York. She specializes in the treatment of patients with multiple myeloma, smoldering myeloma, and related plasma cell disorders. Dr. Shah's clinical and translational research focuses on nutritional and metabolic factors in plasma cell disorders, as well as immune therapies. She is studying the link between nutrition and myeloma via immune, epigenetic, and microbiome mechanisms. In 2021, Dr. Shah opened the first nutrition trial in plasma cell disorders to date, the NUTRIVENTION study, which is currently enrolling, and she has several other NUTRIVENTION studies in development that will open in 2022.
For More Information
Shah U & Ailawadhi S (2022). Hematologic malignancies—plasma cell dyscrasias. Presented at: 2022 ASCO Annual Meeting.
Yee A, Nadeem O, Rosenblatt J, et al (2022). A phase 2 study of daratumumab with weekly carfilzomib, pomalidomide, and dexamethasone in relapsed and refractory multiple myeloma. J Clin Oncol (ASCO Annual Meeting Abstracts), 40(suppl_16). Abstract 8012. DOI:10.1200/JCO.2022.40.16_suppl.8012
Suvannasankha A, Bahlis NJ, Trudel S, et al (2022). Safety and clinical activity of belantamab mafodotin with pembrolizumab in patients with relapsed/refractory multiple myeloma (RRMM): DREAMM-4 Study. J Clin Oncol (ASCO Annual Meeting Abstracts), 40(suppl_16). Abstract 8018. DOI:10.1200/JCO.2022.40.16_suppl.8018
Lonial S, Grosicki S, Hus M, et al (2022). Synergistic effects of low-dose belantamab mafodotin in combination with a gamma-secretase inhibitor (nirogacestat) in patients with relapsed/refractory multiple myeloma (RRMM): DREAMM-5 study. J Clin Oncol (ASCO Annual Meeting Abstracts), 40(suppl_16). Abstract 8019. DOI:10.1200/JCO.2022.40.16_suppl.8019
Quach H, Gironella M, Lee C, et al (2022). Safety and clinical activity of belantamab mafodotin with lenalidomide plus dexamethasone in patients with relapsed/refractory multiple myeloma (RRMM): DREAMM-6 arm-A interim analysis. J Clin Oncol (ASCO Annual Meeting Abstracts), 40(suppl_16). Abstract 8017. DOI:10.1200/JCO.2022.40.16_suppl.8017
van de Donk NWCJ, Moureau P, Delforge M, et al (2022). Comparative efficacy of teclistamab (tec) versus current treatments (tx) in real-world clinical practice in the prospective LocoMMotion study in patients (pts) with triple-class exposed (TCE) relapsed/refractory multiple myeloma (RRMM). J Clin Oncol (ASCO Annual Meeting Abstracts), 40(suppl_16). Abstract 8016. DOI:10.1200/JCO.2022.40.16_suppl.8016
Rytlewski J, Fuller J, Mertz DR, et al (2022). Correlative analysis to define patient profiles associated with manufacturing and clinical endpoints in relapsed/refractory multiple myeloma (RRMM) patients treated with idecabtagene vicleucel (ide-cel; bb2121), an anti-BCMA CAR T cell therapy. . J Clin Oncol (ASCO Annual Meeting Abstracts), 40(suppl_16). Abstract 8021. DOI:10.1200/JCO.2022.40.16_suppl.8021
Minnema MC, Krishnan AY, Berdeja JG, et al (2022). Efficacy and safety of talquetamab, a G protein-coupled receptor family C group 5 member D x CD3 bispecific antibody, in patients with relapsed/refractory multiple myeloma (RRMM): updated results from MonumenTAL-1. J Clin Oncol (ASCO Annual Meeting Abstracts), 40(suppl_16). Abstract 8015: DOI:10.1200/JCO.2022.40.16_suppl.8015
Einsele H, Cohen AD, Delforge M, et al (2022). Biological correlative analyses and updated clinical data of ciltacabtagene autoleucel (cilta-cel), a BCMA-directed CAR-T cell therapy, in lenalidomide (len)-refractory patients (pts) with progressive multiple myeloma (MM) after 1–3 prior lines of therapy (LOT): CARTITUDE-2, cohort A. J Clin Oncol (ASCO Annual Meeting Abstracts), 40(suppl_16). Abstract 8020. DOI:10.1200/JCO.2022.40.16_suppl.8020
Touzeau C, Krishnan AY, Moreau P, et al (2022). Efficacy and safety of teclistamab (tec), a B-cell maturation antigen (BCMA) x CD3 bispecific antibody, in patients (pts) with relapsed/refractory multiple myeloma (RRMM) after exposure to other BCMA-targeted agents. J Clin Oncol (ASCO Annual Meeting Abstracts), 40(suppl_16). Abstract 8013. DOI:10.1200/JCO.2022.40.16_suppl.8013
Oncology Data Advisor (2022). Can Diet and Nutrition Impact Multiple Myeloma Outcomes? Food for Thought From Urvi Shah, MD, and Rahul Banerjee, MD. Available at: https://oncdata.com/news/can-diet-and-nutrition-impact-multiple-myeloma-outcomes-food-for-thought-from-urvi-shah-md-and-rahul-banerjee-md
Rodriguez C, Kaufman JL, Laubach J et al. (2022). Daratumumab (DARA) + lenalidomide, bortezomib, and dexamethasone (RVd) in transplant-eligible newly diagnosed multiple myeloma (NDMM): A post hoc analysis of sustained minimal residual disease (MRD) negativity from GRIFFIN. J Clin Oncol (ASCO Annual Meeting Abstracts), 40 (suppl_16). Abstract 8011. DOI:10.1200/JCO.2022.40.16_suppl.8011
Shah UA, Alicea D, Adintori PA, et al (2021). A pilot plant-based dietary intervention in overweight and obese patients with monoclonal gammopathy of undetermined significance and smoldering multiple myeloma- the Nutrition Prevention (NUTRIVENTION) study. Blood (ASH Annual Meeting Abstracts), 138(suppl_1). Abstract 4759. DOI:10.1182/blood-2021-151049
HealthTree Foundation (2022). Available at: https://healthtree.org/
Clinicaltrials.gov (2022). A study of health-related quality of life in people with multiple myeloma receiving daratumumab or lenalidomide. NLM identifier: NCT04497961.
Transcript edited for clarity. Any views expressed above are the speaker's own and do not necessarily reflect those of Oncology Data Advisor.