Frontline Combos Take the Spotlight: Previewing the Top Hematologic Oncology Presentations at ASCO 2026

With the 2026 ASCO Annual Meeting just over a week away, it’s time to look ahead to the most anticipated hematologic oncology presentations set to take the stage. To help preview the key abstracts in multiple myeloma, myeloproliferative neoplasms (MPNs), large B-cell lymphoma (LBCL), chronic lymphocytic leukemia, and more, OncLive® asked experts to share which presentations they’re most looking forward to seeing at the meeting.

Insights were shared by:

• Diana Cirstea, MD, an attending physician in the Center for Multiple Myeloma at Massachusetts General Hospital, as well as an assistant professor of medicine at Harvard Medical School, in Boston, Massachusetts
• Andrew Kuykendall, MD, an assistant member in the Department of Malignant Hematology at Moffitt Cancer Center in Tampa, Florida
• Aaron Gerds, MD, MS, a physician in the Department of Hematology and Medical Oncology at Cleveland Clinic, as well as an assistant professor in the Department of Medicine of the School of Medicine, deputy associate director for Clinical Research, and member of the Developmental Therapeutics Program at Case Comprehensive Cancer Center of Case Western Reserve University, in Ohio
• Anthony M. Hunter, MD, an associate professor in the Department of Hematology and Medical Oncology at Emory University School of Medicine, medical director of the Immediate Care Center, and leader of the Myeloproliferative Neoplasm Program at Emory Winship Cancer Institute in Atlanta, Georgia
• Tycel Phillips, MD, an associate professor in the Department of Hematology and Hematopoietic Cell Transplantation in the Division of Lymphoma at City of Hope in Duarte, California
• Lore Gruenbaum, PhD, chief scientific officer and senior vice president of Research at Blood Cancer United
• Brad S. Kahl, MD, a professor of medicine in the Division of Oncology and director of the Lymphoma Program at Washington University School of Medicine in St. Louis, Missouri
• Paolo Strati, MD, an associate professor in the Department of Translational Molecular Pathology of the Division of Cancer Medicine and an associate professor in the Department of Lymphoma/Myeloma at The University of Texas MD Anderson Cancer Center in Houston, as well as an international faculty member in the Department of PhD program in Clinical and Experimental Oncology and Immunology at the University of Padova in Padua

Multiple Myeloma

DREAMM-9 final analysis: Belantamab mafodotin (belamaf), bortezomib, lenalidomide, and dexamethasone (BVRd) for transplant-ineligible (TI) newly diagnosed multiple myeloma (NDMM)

Presentation time: May 29, 2026, 3:45 pm CT

Belantamab mafodotin with daratumumab, lenalidomide, and dexamethasone in transplant-ineligible, newly diagnosed multiple myeloma patients: Phase 1/2 BelaDRd study

Presentation time: May 31, 2026, 10:15 am CT

Cirstea: We have quite a few presentations on belantamab mafodotin-blmf [Blenrep]. One of the presentations I'm looking forward to is the [phase 3] DREAMM-9 [trial (NCT04091126)] by Saad Z. Usmani, MD, MBA, FACP, FASCO, [of Memorial Sloan Kettering Cancer Center in New York, New York]. The [phase 3] DREAMM-7 [NCT04246047] and DREAMM-8 [NCT04484623] trials reestablished belantamab-based therapy as clinically relevant in [the] early-relapse [setting], with DREAMM-7 comparing belantamab mafodotin plus bortezomib [Velcade] and dexamethasone [Vd] against daratumumab [Darzalex] plus Vd [DVd], and then DREAMM-8 showed [benefit with] belantamab mafodotin plus pomalidomide [Pomalyst] plus dexamethasone over pomalidomide plus Vd [PVd].

Two trials evaluating belantamab-based quadruplets up-front will have their data [presented] at ASCO 2026. DREAMM-9 is looking at belantamab plus lenalidomide [Revlimid] and Vd, and the other trial, the phase 1/2 [BelaDRd] study [EUCT-2024-515634-32], is looking at belantamab plus DRd. These trials now ask the more important frontline question: can belantamab mafodotin be safely integrated into modern [treatment] for patients with transplant-ineligible, newly diagnosed myeloma, where we already know that daratumumab-based quadruplets are doing such a great job? Then the question is: How are ocular toxicities managed? What is the minimal residual disease [MRD] durability? I'm really curious and looking forward to this data.

MajesTEC-9: A phase 3 randomized study of teclistamab monotherapy vs investigator’s choice of pomalidomide, bortezomib, and dexamethasone or carfilzomib and dexamethasone (PVd/Kd) in patients (pts) with relapsed refractory multiple myeloma (RRMM)

Presentation time: May 29, 2026, 4:57 pm CT

Cirstea: [The phase 3] MajesTEC-9 trial [NCT05572515] is arguably one of the most practice-relevant ASCO 2026 studies because it basically shifts [a bispecific antibody] up from a salvage therapy to an early-relapse immune therapy option as monotherapy, not as a daratumumab/teclistamab-cqyv [Tecvayli] combination. In MajesTEC-9, teclistamab monotherapy was compared with PVd or carfilzomib [Kyprolis] plus dexamethasone after 1 to 3 previous lines of therapy in a population that was previously exposed to an anti-CD38 antibody and lenalidomide. The important aspect here is that these are patients who have seen anti-CD38 monoclonal antibody therapy, as opposed to the phase 3 MajesTEC-3 trial [NCT05083169], where only approximately 5% of patients in those cohorts were [previously] exposed to daratumumab.

The topline reporting already indicates a very encouraging progression-free survival [PFS] and overall survival [OS] with [teclistamab] as compared with the standard regimens.¹ Now, the question is, how safe is it? What's the infection risk, and would it be feasible to implement that in the community setting, given the step-up dosing logistics? What's the benefit across early-relapse subgroups and high-risk groups, as opposed to standard ones? That will be very interesting data.

Mezigdomide, carfilzomib, and dexamethasone (MeziKd) vs carfilzomib and dexamethasone (Kd) in relapsed/refractory multiple myeloma (RRMM): Results from the phase 3 SUCCESSOR-2 trial

Presentation time: May 29, 2026, 4:45 pm CT

Cirstea: The [phase 3] SUCCESSOR-2 trial [NCT05552976] will be presented by Paul G. Richardson, MD, [of Dana-Farber Cancer Institute in Boston, Massachusetts]. Here we ask the question whether mezigdomide [CC-92480] may rescue the post-lenalidomide, post-CD30 backbone problem. What's the role of CELMoDs? Will they overcome the resistance to immunomodulatory drugs like lenalidomide and pomalidomide?

MPNs

Selinexor plus ruxolitinib in JAK inhibitor–naïve myelofibrosis: Phase 3 SENTRY trial.

Presentation time: June 2, 2026, 9:45 am CT

Kuykendall: ASCO has become a place where some exciting [MPN] trials do get presented. Last year, we presented the phase 3 VERIFY study [NCT05210790] looking at polycythemia vera. This year, the excitement's around a few different studies. We have the [phase 3] SENTRY study [NCT04562389], looking at selinexor [Xpovio] plus ruxolitinib [Jakafi]—the most recent combination strategy in myelofibrosis. We have a press release describing those results, but we don't have much more than that.² The press release was actually quite provocative, where we saw [statistically significant] spleen volume improvements, [but] didn't hit [statistically significant] symptom [improvements]. We're used to that story [in myelofibrosis], but we saw this weird OS benefit, which I don't think we were expecting. Certainly, a lot of people want some clarity on that, and I think I'll be excited to see that presentation.

Gerds: One thing that's kind of bubbling up [where] we really want to see some results is the up-front study comparing ruxolitinib plus selinexor vs ruxolitinib plus placebo in patients [with myelofibrosis] who are treatment naive. Over the last couple of years, we have seen a number of large prospective, randomized, phase 3 trials fall short in this area. We had navitoclax [ABT-263], as well as pelabresib (CPI-0610), that had much better spleen volume responses, but didn't hit on key secondary end points of symptom burden improvements, and those trials also failed to show a survival advantage. When you want to get a new drug approved, you have to do 1 of 2 things: you have to prove that it makes people feel better, or you have to prove that it makes people live longer. If we want to break it that down quite simply, even though [navitoclax and pelabresib each] shrunk spleens to a massive degree greater than just ruxolitinib alone, they didn't improve symptoms, and then there's no survival signal from those studies yet.

Selinexor is already being approved for multiple myeloma, so it has already had some success in getting regulatory approval. They showed in this press release that [ruxolitinib plus selinexor] did improve spleen volume response. It did not improve symptom responses over ruxolitinib alone, but the combination was leading to a better survival outcome, even very early on in the study, which was quite surprising. That might be the difference. If it hits on spleen volume and survival, maybe we're okay if it doesn't hit on symptoms. At the end of the day, ruxolitinib by itself is a very good drug at treating symptoms in [myelofibrosis]. Why would we expect a combination to do even better than that? We need more to get these new and innovative therapies across the regulatory threshold.

Hunter: The one that we're most excited and interested to see is going to be the SENTRY trial with selinexor. We've seen some of the [outcomes] in the initial press release, but we haven't really seen the full data for that phase 3 study yet. This [trial] fits into the broader [idea] of moving the field forward with some sort of combination therapy in myelofibrosis. For treatment-naive patients [treated with] with ruxolitinib plus selinexor, we have seen the press release [showing] that [the trial] did meet the end point for spleen responses, but not for symptoms. There [were also] some early survival signals. That's probably the biggest one to look forward to at ASCO. It’s a really a big study that we’re anxious to see the full data for.

RALLY-MF: Initial efficacy of a phase 2 study of DISC-0974, an anti-hemojuvelin antibody, to treat anemia in myelofibrosis

Presentation time: June 2, 2026, 9:57 am CT

Kuykendall: We’re continuing to see data for DISC-0974, which is an anemia agent in myelofibrosis. We've had trouble getting anemia agents over the line in this space, and perhaps this is the newest, best-in-class [agent]. We've seen the data [from the phase 2 RALLY-MF trial (NCT05320198)] presented before, but every time more data come out, we're starting to see a considerable number of patients on that study.

Hunter: There will be some data from the phase 2 portion of the RALLY-MF study with DISC-0974, a hemojuvelin antibody study that we're part of here at Emory, and we have seen some nice responses so far. [DISC-0974] is an anemia drug that's shown some promise. We look forward to seeing some more data from that [study].

A phase 2 study of fedratinib in patients with MDS/MPN and chronic neutrophilic leukemia.

Presentation time: May 30, 2026, 1:15 pm CT

Kuykendall: I'll also put a plug in for a lovely study, an investigator-initiated [phase 2] trial [NCT05177211], looking at myelodysplastic syndrome/MPN overlaps, using fedratinib [Inrebic].

Diffuse Large B-Cell Lymphoma

frontMIND: Phase 3 study of tafasitamab (Tafa) plus lenalidomide (Len) and R-CHOP for patients (pts) with newly diagnosed diffuse large B-cell lymphoma (DLBCL)

Presentation time: May 30, 2026, 3:00 pm CT

Phillips: The top of the list will likely be the [phase 3] frontMIND study [NCT04824092], which is a study of tafasitamab-cxix (Monjuvi) plus lenalidomide (Revlimid) and R-CHOP [rituximab (Rituxan) plus cyclophosphamide, doxorubicin, vincristine, and prednisone] for patients with newly diagnosed diffuse large B-cell lymphoma [DLBCL]. This is the first of likely several of entries into the frontline space for LBCL. For the longest time, all we had was R-CHOP. More recently we had, the phase 3 POLARIX study [NCT03274492] that evaluated polatuzumab vedotin-piiq [Polivy] plus R-CHP. Now, we could have 6 or 7 options, which is something that we would have thought was unheard of just a couple years ago [for frontline DLBCL management].

Strati: Everybody in the lymphoma community has been waiting for the first public disclosure of results from the frontMIND trial. The frontMIND trial is a randomized phase 3 trial comparing R-CHOP with tafasitamab plus lenalidomide and R-CHOP for patients with previously untreated DLBCL with advanced stage disease.

frontMIND could be the third randomized phase 3 positive study in the frontline setting for DLBCL. As a reminder, tafasitamab is different from polatuzumab, which is an antibody-drug conjugate, [tafasitamab] is a naked monoclonal antibody targeting CD19. We learned from the press release that the trial met its primary end point, which means that later this year or early in 2027 we may be able to prescribe tafasitamab in the frontline setting [for DLBCL].³ As of now, we can only prescribe tafasitamab in combination with lenalidomide in the second-line setting in lymphoma.

[The frontMIND study] brings up some big questions that will be finally answered at ASCO. How big is the advantage in terms of progression-free survival [PFS] as compared with R-CHOP? If [the advantage] is still limited, there is a chance that even if we will get an FDA label and an approval, some providers may not be excited about prescribing [tafasitamab].

[Another] big question is, we target CD19 the same way tafasitamab does in the second line through CAR T-cell therapy. Autologous anti-CD19 CAR T-cell therapies are currently approved by the FDA in second-line for patients who are chemotherapy-refractory DLBCL or chemotherapy-sensitive and ineligible for autologous stem cell transplant. However, if we target CD19 in the frontline, is the fraction of patients who will relapse in second-line who are CD19-negative? Is this going to impact the activity of a potentially curative treatment option in the second line? Or will that not matter, because maybe we're going to cure more patients in the frontline?

Gruenbaum: [The frontMIND study] is looking at the combination of tafasitamab and lenalidomide, added to what is the current standard of care [SOC], R-CHOP, as the backbone, and it is interesting. We saw topline results announced at the start of this year, and this study met its primary end point, demonstrating improved PFS and did not identify new safety concerns in terms of the addition of these 2 agents. [frontMIND] was a study that includes patients who are high-risk, as well. For context, it's important to know we have R-CHOP now as a well-established SOC, but roughly 40% of patients do relapse after R-CHOP. We’re in a good situation with great options available also in second- and later-lines of therapy, but first and foremost, if we can bring a patient to long-term remission or possibly to cure in the frontline, that is the goal. There's an interesting question out there on whether the addition of these 2 agents could be really leading to a new SOC possibly for some of these newly diagnosed patients.

Kahl: This was a randomized clinical trial in first-line DLBCL where patients with high-risk disease by International Prognostic Index scores were randomly assigned to either R-CHOP or R-CHOP combined with tafasitamab and lenalidomide, and the trial finished enrolling a couple of years ago. It's a positive study favoring the experimental arm. [Therefore], it'll be interesting to see that data and the magnitude of the difference, to look at the toxicity profiles, and then try to decide if there are patients in my practice who should get this R-CHOP combination [with tafasitamab and lenalidomide].

There might be some patients that you might be favoring R-CHOP that you [will now] instead favor R-CHOP plus tafasitamab and lenalidomide. [The frontMIND regimen] could represent a new first-line treatment option for selected patients.

Phase 2 trial of epcoritamab in combination with rituximab-mini CVP for older unfit/frail or anthracycline-ineligible adult patients with newly diagnosed diffuse large B-cell lymphoma: Interim futility analysis

Presentation time: May 30, 2026. 3:24 pm CT

Phillips: The unexplored frontier in LBCL at this point is the best management for patients who are older and unfit, or who aren't great candidates for full-dose R-CHOP. We saw several articles and abstracts presented at the 2025 ASH Annual Meeting and Exposition, and this is just a follow up to that to see if there's another entryway into this space. In the next couple of years, most of the clinical trials we're going to see will be focused on older, unfit, frail and anthracycline ineligible patient population. The results of this study will be quite interesting to see how it plays out.

Strati: This study is removing the anthracycline by changing R-CHOP to R-cyclophosphamide, vincristine [Oncovin], and prednisone [miniCVP]. [This study is] going to decrease R-CHOP and remove doxorubicin by adding epcoritamab-bysp [Epkinly] for patients who are old and frail. [There] be amazing results at the oral presentation. The common theme for the lymphoma session at ASCO this year will be trying to make more effective and potentially less toxic by frontline regimens by minimizing chemotherapy through the implementation of new biological agents such as epcoritamab, tafasitamab, and others.

Classical Hodgkin Lymphoma

A phase 1 study of the PRMT5 inhibitor AZD3470 in patients with relapsed/refractory classic Hodgkin lymphoma (PRIMAVERA)

Presentation time: May 30, 2026, 4:00 pm CT

Phillips: I'm looking forward to the [phase 1 PRIMAVERA] study [NCT06137144] because there's been little research into relapsed or refractory Hodgkin lymphoma since the approval of checkpoint inhibitors. This could be quite a pivotal moment given the lack of options we've seen in this space in the last couple years. If you talk to people who devote a lot of their interest and research into Hodgkin lymphoma, they will speak about the lack of options that we have in this [relapsed/refractory] space. The last real promising agent was camidanlumab tesirine [ADCT-301], which unfortunately was pulled because of high rates of Guillain-Barré syndrome. I'll be interested in this abstract, even though it's phase 1, because it'll be quite helpful to have a new entrant in this space because we've [become] spoiled by curing so many patients with Hodgkin lymphoma. [However], patients who don't respond to frontline initial therapy or salvage treatment are still a difficult-to-treat patient population. We need more research to sort of explore options for classical Hodgkin lymphoma.

T-Cell Acute Lymphocytic Leukemia/Peripheral T-Cell Lymphoma

First-in-human dual-epitope nanobody anti-CD5 CAR-T for relapsed/refractory T-ALL/PTCL: Phase I dose-escalation and expansion results from the CONQUER trial

Presentation time: June 2, 2026, 3:24 pm CT

Gruenbaum: [The phase 1/2 CONQUER trial (NCT06874946)] evaluates a novel dual epitope nanobody anti-CD5 CAR T-cell therapy. It is a CAR T-cell therapy that is directed against 2 different sides on CD5, and this was done to avoid one of the biggest risks and challenges in CAR T-cell therapy for T-cell malignancies. CAR-T cells that target malignant T-cells may also target their fellow CAR T cells. [CAR T-cell therapies targeting fellow CAR T cells] is something that we want to avoid. The design with this dual-epitope nanobody specifically was chosen to avoid this fratricide of CAR T cells without having to resort to gene editing. It's an intricate mechanism to block access to CD5 on those CAR T cells so that they are protected from basically attacking each other. We're going to see data from a dose escalation and early expansion, we may see some data also for cutaneous T-cell lymphoma, including the mycosis fungoides, where efficacious treatments are really lacking. It’s of note that there are other approaches out there in the CAR T-cell therapy space targeting CD5, including with a CD5 knockout on the CAR T cells that are actively being pursued to improve their functionality.

References

1. Tecvayli monotherapy demonstrates superior progression-free and overall survival versus standard of care as early as first relapse in patients with multiple myeloma predominantly refractory to anti-CD38 therapy and lenalidomide. Johnson and Johnson. News Release. January 14, 2026. Accessed May 20, 2026. https://www.jnj.com/media-center/press-releases/tecvayli-monotherapy-demonstrates-superior-progression-free-and-overall-survival-versus-standard-of-care-as-early-as-first-relapse-in-patients-with-multiple-myeloma-predominantly-refractory-to-anti-cd38-therapy-and-lenalidomide
2. Karyopharm's phase 3 SENTRY trial in myelofibrosis met first co-primary endpoint, demonstrating statistically significant improvement in spleen volume reduction. News release. Karyopharm Therapeutics. March 24, 2026. Accessed May 20, 2026. https://investors.karyopharm.com/2026-03-24-Karyopharms-Phase-3-SENTRY-Trial-in-Myelofibrosis-Met-First-Co-Primary-Endpoint,-Demonstrating-Statistically-Significant-Improvement-in-Spleen-Volume-Reduction
3. Incyte announces positive topline results from pivotal study of tafasitamab (Monjuvi/Minjuvi) as a first-line treatment for diffuse large B-cell lymphoma. Incyte. New Release. January 5, 2026. Accessed May 20, 2026. https://investor.incyte.com/news-releases/news-release-details/incyte-announces-positive-topline-results-pivotal-study-0