Hematologists Highlight Top Data From ASCO 2026

Key hematologic oncology data drew attention at the 2026 ASCO Annual Meeting, with key phase 3 trials reading out across the multiple myeloma, diffuse large B-cell lymphoma (DLBCL), and myelofibrosis settings. Experts helped outline some of the top hematology findings shared at the meeting and what these findings may mean for clinical practice.

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).

Teclistamab-cqyv (Tecvayli) monotherapy generated statistically significant improvements in progression-free survival (PFS) and overall survival (OS) compared with investigator’s choice of pomalidomide (Pomalyst) plus bortezomib (Velcade) and dexamethasone (PVd) or carfilzomib (Kyprolis) plus dexamethasone (Kd) in patients with relapsed/refractory multiple myeloma who had received 1 to 3 prior lines of therapy that included daratumumab (Darzalex) and lenalidomide (Revlimid) in the phase 3 MajesTEC-9 trial (NCT05572515).¹

Findings showed teclistamab (n = 296) reduced the risk of disease progression or death by 71% compared with the standard-of-care (SOC) regimens (n = 297; HR, 0.29; 95% CI, 0.23-0.38; P < .0001). The median PFS was not reached (NR) in the experimental arm vs 8.2 months in the control arm. The estimated 18-month PFS rates were 69.8% for teclistamab compared with 26.9% for SOC. Additionally, teclistamab reduced the risk of death by 40% compared with SOC (HR, 0.60; 95% CI, 0.43-0.83; P = .0020). The median OS was NR in both arms, but the estimated 18-month OS rates were 79.2% and 68.6% for teclistamab and SOC, respectively.

Saad Usmani, MD, MBA, FACP, FASCO

Memorial Sloan Kettering Cancer Center

“We had 2 clinical trials in the relapsed setting read out [at ASCO 2026] that had a high proportion of patients who are daratumumab- and lenalidomide-refractory. One clinical trial is [MajesTEC-9 with] teclistamab monotherapy compared with SOC regimens...I’m especially encouraged by the monotherapy teclistamab data. It’s relevant to our clinical practice because many patients get daratumumab and lenalidomide exposure [and then] refractoriness nowadays at the time of relapse.”

Rahul Banerjee, MD, FACP

Fred Hutchinson Cancer Center

“In my practice, for the past 4 years, [all] patients [have been] receiving an anti-CD38 [agent] as part of their induction in the modern era. What do you do with those patients [at relapse]? Do you keep the daratumumab going? Do you use teclistamab plus daratumumab, or teclistamab by itself? We didn’t know. Now we know that teclistamab by itself does carry a punch in these patients. We saw improved rates of complete response [CR], improved minimal residual disease negativity, and improves PFS; that’s remarkable. Will it change how we use the drug? Not directly, so to speak—teclistamab has already been approved [after] 1 prior line [of therapy], but the approval has remained for teclistamab plus daratumumab as a doublet. For patients who can get both, where it makes sense to offer both, I do…. This is not a competition between the 2 [regimens]. Daratumumab probably does add some myeloma activity…. However, if a patient is daratumumab refractory and you had doubts about whether teclistamab monotherapy works, you should no longer have any doubts, because MajesTEC-9 showed that it does work and works quite well.”

frontMIND: Phase 3 study of tafasitamab plus lenalidomide and R-Chop for patients with newly diagnosed diffuse large B-cell lymphoma.

Findings from the phase 3 frontMIND trial (NCT04824092) demonstrated that tafasitamab-cxix (Monjuvi) administered in combination with lenalidomide and R-CHOP (rituximab [Rituxan], cyclophosphamide, doxorubicin, vincristine, and prednisone) led to a statistically significant improvement in PFS compared with R-CHOP alone in patients with newly diagnosed, high-risk DLBCL.²

At a median follow-up of 35.2 months, investigators reported a 25% reduction in the risk of disease progression or death with the tafasitamab-based regimen (n = 448) compared with R-CHOP alone (n = 451; HR, 0.75; 95% CI, 0.59-0.96; P = .0194). Patients treated with tafasitamab plus lenalidomide and R-CHOP experienced 2- and 3-year PFS rates of 71.1% and 67.3%, respectively. These respective rates were 62.9% and 60.7% for R-CHOP alone.

Sonali M. Smith, MD

University of Chicago Medicine

“[These data] are really important, because when we think historically, trying to beat R-CHOP in an all-comers trial has been exceedingly difficult, and now we have the second positive trial—the first one being [the phase 3] POLARIX study [NCT03274492]. I think a couple of notable findings from the frontMIND trial are that they enrolled really high-risk patients—with International Prognostic Index [scores of] 3 to 5—and when you look at the patient characteristics, there were some significant adverse risk factors that were included. Our dream [would be] to someday go to a chemotherapy-free approach and regimen [in the frontline setting]. There are some really great initiatives ongoing, including looking at completely chemotherapy-free or chemotherapy-light approaches. I think we are going to get there. Right now, everybody is still building on a chemotherapy backbone, but getting to a chemotherapy-free regimen is getting closer as we see the activity of some of these targeted agents.”

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

The addition of the XPO1 inhibitor selinexor (Xpovio) to ruxolitinib (Jakafi) yielded a statistically significant improvement in spleen volume reduction (SVR) by week 24 compared with ruxolitinib plus placebo in patients with JAK inhibitor–naive myelofibrosis, meeting a co-primary end points of the phase 3 SENTRY trial (NCT04562389).³ The study did not meet its other co-primary end point of absolute total symptom score (TSS) from baseline to week 24, although meaningful reductions in symptom burden were reported in both arms.

At week 24, 49.8% of patients in the selinexor-plus-ruxolitinib arm (n = 235) experienced an SVR of at least 35% compared with 28.0% of patients treated with ruxolitinib plus placebo (n = 118; difference, 21.8%; odds ratio, 2.58; 95% CI, 1.60-4.17; 1-sided P < .0001). At week 24, the change in absolute TSS was –9.9 (95% CI, –11.2 to –8.6) in the selinexor arm vs –10.9 (95% CI, –12.6 to –9.1) in the placebo arm (adjusted mean difference, 0.97; 95% CI, –1.07 to 3.02; 1-sided P = .825).

Notably, at a median follow-up of 11.6 months for the selinexor arm and 12.6 months for the placebo arm, an OS trend favoring the experimental combination was reported (HR, 0.43; 95% CI, 0.19-1.00; nominal 1-sided P = .022). OS data remained immature at the time of this analysis, with an event rate of 4.7% in the experimental arm vs 10.2% in the control arm.

John Mascarenhas, MD

Tisch Cancer Center at Mount Sinai

“There was no clear subgroup that was benefiting from [selinexor] more than others, so [the combination] worked across the subgroups of patients. The physician, with the patient, would have to make a decision about whether combination therapy is appropriate, but it [would be] nice to have that option, particularly if you’re trying to go for deeper spleen responses. Maybe you’re trying to get a patient to transplant where you want a deeper, more rapid spleen response, or patients might be younger with an eye on survival, [with] the idea that one could potentially get deeper responses that could translate to better survival.”

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

The addition of the CELMoD mezigdomide (CC-92480) to Kd improved PFS vs Kd alone in patients with multiple myeloma who had received at least 1 prior line of therapy and were exposed/refractory to an anti-CD38 monoclonal antibody and lenalidomide, according to data from the phase 3 SUCCESSOR-2 trial (NCT05552976).⁴

Data demonstrated that at a median follow-up of 10.6 months, patients treated with the triplet (n = 288) achieved a median PFS of 18.0 months compared with 8.3 months for those given Kd alone (n = 191; HR, 0.48; 95% CI, 0.36-0.63; P < .0001). Mezigdomide-based therapy also produced an overall response rate of 80.2% compared with 53.4% for Kd alone, along with improvements in CR or better rate (26.7% vs 8.9%, respectively) and very good partial response or better rate (60.1% vs 30.9%, respectively).

Saad Usmani, MD, MBA, FACP, FASCO

Memorial Sloan Kettering Cancer Center

“The [SUCCESSOR-2] study [evaluated] mezigdomide [plus] Kd compared with Kd. Having mezigdomide potentially as an option, if it gets a regulatory approval later [in 2026] or next year, would be welcome for patients who might be receiving BCMA-directed treatments early on and may have been exposed to lenalidomide and pomalidomide in the past. We can utilize the mezigdomide combination for those patients.”

Rahul Banerjee, MD, FACP

Fred Hutchinson Cancer Center

“[This mezigdomide-based regimen is] not yet FDA approved, but hopefully will be soon. It’s not immediately practice-changing, but it’s a good glimpse of where the field is headed very imminently. Mezigdomide and iberdomide [CC-220] are examples of CELMoDs. CELMoDs are a new class of oral medications for myeloma that work extremely well. They have some similarity with the older immunomodulatory drugs [IMiDs] that we all know and love—for example, lenalidomide or pomalidomide,—but everything an IMiD could dream of doing, a CELMoD can do harder, faster, better, and stronger…. In this study, mezigdomide plus Kd beat Kd. It was a triplet vs a doublet, and you could argue that we don’t use Kd much in the US anymore as a doublet, and that is indeed true. On the other hand, KPd, which we sometimes do use in the US, is not approved anywhere in the world. Our hope is that finally, as a result of this study and the hard work that the patients and the investigators put into it, mezigdomide plus Kd will be approved, and that will be amazing in its own right. I plan to use CELMoDs immediately; as soon as I can get my hands on them commercially, my patients will start receiving them, and then we can use them as a backbone for other studies.”

References

1. Mina R, Touzeau C, Hungria V, et al. 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). J Clin Oncol. 2026;44(suppl 16):7507. doi:10.1200/JCO.2026.44.16_suppl.7507
2. Lenz G, Trněný M, Burke JM, et al. frontMIND: phase 3 study of tafasitamab plus lenalidomide and R-CHOP for patients with newly diagnosed diffuse large B-cell lymphoma. J Clin Oncol. 2026;44(suppl 17):LBA7000. 10.1200/JCO.2026.44.17_suppl.LBA7000
3. Mascarenhas J, Ali H, Al-Ali H, et al. Selinexor plus ruxolitinib in JAK inhibitor–naïve myelofibrosis: phase 3 SENTRY trial. J Clin Oncol. 2026;44(suppl 17):LBA6500. doi:10.1200/jco.2026.44.17_suppl.LBA6500
4. Richardson P, Schjesvold F, Chengcheng F, et al. Mezigdomide, carfilzomib, and dexamethasone (MeziKd) vs carfilzomib and dexamethasone (Kd) in relapsed/refractory multiple myeloma (RRMM): results from the phase 3 SUCCESSOR-2 trial. J Clin Oncol. 2026;44(suppl 17):7506. doi:10.1200/JCO.2026.44.17_suppl.LBA7506