Welcome to The Five Under 5, your go-to roundup of the top 5 videos of the week.
These short videos are designed for busy oncologists to view on the go, and feature expert insights on breaking news, regulatory updates, practice-changing data shared at medical meetings, and other key topics in the realm of oncology.
Here’s what you may have missed:
Novel Methodology to Measure Progress in Blood Cancers: E. Anders Kolb, MD
E. Anders Kolb, MD, of Blood Cancer United, examined a life-years-saved methodology developed to quantify the impact of therapeutic innovation on survival in blood cancers, and explained why the approach captures progress that mortality statistics alone can miss. Kolb noted that most of the decline in overall cancer mortality since 1991 is attributable to prevention and screening efforts—neither of which applies meaningfully to blood cancers, where progress stems primarily from therapeutic innovation and access to those therapies. The life-years-saved analysis, published in Blood Advances, compared general population life expectancy against life expectancy after a blood cancer diagnosis, with the difference calculated by age cohort to yield life-years lost or saved. Kolb explained that the metric translates survival gains into concrete milestones such as birthdays and graduations, while also accounting for the fact that prolonged treatment-related adverse effects can limit life years even in patients not considered cured.
Phase 2 Efficacy and Safety Data for DISC-3405 in Polycythemia Vera: Naseema Gangat, MBBS
Naseema Gangat, MBBS, of Mayo Clinic and the Mayo Clinic Comprehensive Cancer Center, detailed initial data from the ongoing phase 2 RESTORE-PV study (NCT06985147) examining the anti-TMPRSS6 monoclonal antibody DISC-3405 in patients with polycythemia vera (PV), as presented at the 2026 Society of Hematologic Oncology (SOHO) Annual Meeting. Among cohort A patients who completed the first maintenance phase (n = 9), 77.9% became phlebotomy-free; among those who completed 26 weeks of treatment (n = 13), 61.5% were phlebotomy free, with a mean reduction in phlebotomy events from baseline to week 26 of −3.4 (95% CI, −4.5 to −2.3). Gangat framed DISC-3405 as an adjunct to existing PV management, potentially of greatest benefit to patients intolerant of phlebotomy, younger patients wishing to avoid cytoreductive therapy, or those already on cytoreductive therapy who still require frequent phlebotomy. She concluded that the agent may help optimize cytoreductive dosing to eliminate phlebotomy requirements in appropriate patients, with cohort B data still maturing.
Next Steps for Ofirnoflast in Lower-Risk MDS: David Sallman, MD
David Sallman, MD, of Moffitt Cancer Center, outlined final results from a phase 2a trial (NCT07052006) examining the first-in-class allosteric NEK7 inhibitor ofirnoflast (HT-6184) in patients with erythropoiesis-stimulating agent (ESA)–refractory lower-risk myelodysplastic syndrome, as presented at the 2026 SOHO Annual Meeting, and described next steps toward a pivotal phase 3 trial. Before a phase 3 study, Sallman noted that an additional dose-optimization trial (NCT07738510) will assess 2-mg and 3-mg daily doses to identify the optimal efficacy-tolerability balance, with eligibility broadened beyond isolated ESA failure to patients with 1 to 3 previous lines of therapy, including those previously exposed to luspatercept-aamt (Reblozyl). A transfusion independence rate near 40% in that subsequent trial would support a pivotal phase 3 study targeting a 16-week transfusion independence rate above 30%, Sallman said. He also highlighted the potential for combination strategies, noting that ofirnoflast, luspatercept, ESAs, and hypomethylating agents act through distinct, non-overlapping mechanisms. He suggested the agent may have its greatest role earlier in the disease course, before excess blasts or transformation to acute myeloid leukemia (AML) occur.
Potential Role of Selinexor Plus Ruxolitinib in Myelofibrosis: Prithviraj Bose, MD
Prithviraj Bose, MD, of The University of Texas MD Anderson Cancer Center, reviewed data from the phase 3 SENTRY trial (NCT04562389) examining selinexor (Xpovio) paired with ruxolitinib (Jakafi) in patients with JAK inhibitor–naive myelofibrosis, and described where the combination could fit into clinical practice if approved by the FDA. A supplemental new drug application was submitted to the FDA in August 2026 seeking accelerated approval for this indication; if approved, Bose noted the combination would represent the first ruxolitinib-based regimen with a demonstrated survival benefit—an advantage not seen with other investigated combinations, including pelabresib or navitoclax. Bose said he would initially prioritize the regimen for patients with higher-risk disease, particularly those needing potent spleen reduction, those for whom it could serve as a bridge to transplant, and those with higher-risk features where a synergistic approach could better address disease biology, noting that variant allele frequency reductions of at least 20% at week 24 were observed in 32.0% of evaluable patients who received selinexor (n = 169) vs 23.9% given placebo (n = 92). He concluded that although the combination would not immediately become standard of care, it could ultimately be offered to any patient currently eligible for ruxolitinib as comfort with the regimen and maturity of survival data grow.
Dose Optimization and Toxicity Management in Older Patients With AML: Uma Borate, MBBS, MS
Uma Borate, MBBS, MS, of The Ohio State University Comprehensive Cancer Center–James, highlighted the need to optimize dosing and reduce toxicities with existing therapies for older patients with AML, arguing this is equally important as developing novel curative approaches for a population often ineligible for stem cell transplant. Many older patients with AML instead receive indefinite treatment with regimens like venetoclax (Venclexta) plus a hypomethylating agent such as azacitidine (Vidaza), and Borate emphasized that prolonged exposure to toxic regimens can compromise quality of life and daily activities. She proposed fixed-duration, time-limited therapy followed by disease or measurable residual disease monitoring as a potential next frontier worth investigating in older patients with AML. Borate also pointed to a phase 1 trial (NCT03013998) assessing the triplet of azacitidine, venetoclax, and revumenib (Revuforj) in newly diagnosed patients aged 60 and older with NPM1-mutated or KMT2A-rearranged AML as a study to watch for both efficacy and toxicity data.
