Clinical Summary:

• Design/Population: The final analysis of the multi-cohort DREAMM-9 study evaluated belantamab mafodotin plus VRd in transplant-ineligible patients with newly diagnosed multiple myeloma, using different belantamab mafodotin dosing schedules during induction and maintenance.
• Key Outcomes: Quadruplet belantamab mafodotin was feasible and highly active, with high response and MRD negativity rates across cohorts. Efficacy appeared strongest with more intensive induction dosing, particularly every-other-cycle belantamab mafodotin at 1.9 mg/kg, while less frequent maintenance dosing improved tolerability and reduced corneal toxicity.
• Clinical Relevance: These findings support belantamab-based quadruplet therapy as highly active frontline option in transplant-ineligible multiple myeloma and help define optimized dosing schedules for future studies. 

Enrique Ocio, MD, PhD, Hospital Universitario Marqués de Valdecilla, Santander, Spain, discusses results from the final analysis of the DREAMM-9 study evaluating belantamab mafodotin plus bortezomib, lenalidomide, and dexamethasone (VRd) among newly diagnosed multiple myeloma patients who were not candidates for autologous stem cell transplantation. The study explored multiple belantamab dosing schedules to balance efficacy and long-term tolerability.

The regimen produced high response and deep remission across cohorts, with particularly impressive MRD negativity rates in patients receiving belantamab mafodotin every other cycle during induction. Extended dosing intervals during maintenance improved tolerability, particularly by reducing corneal toxicity. These findings support a strategy of more intensive early treatment followed by less frequent maintenance. 

Dr Ocio presented these results at the EHA Congress in Stockholm, Sweden.

Transcript:

Hello, my name is Enrique Ocio, I'm from the University Hospital Marqués de Valdecilla, in Santander in Spain. I will present to you the main results, the main data, on the presentation I gave a couple of days ago at EHA meeting in Stockholm. 

These were the final results, final analysis, of the DREAMM-9 study that evaluated a quadruplet combination with belantamab mafodotin (belamaf), belamaf-VRD in newly diagnosed myeloma patients who are not candidates for stem cell transplantation.

We know that the introduction of quadruplets has revolutionized treatment of newly diagnosed myeloma patients, both eligible and ineligible to autologous stem cell transplantation. These quadruplets are based on anti- CD13 monoclonal antibodies, bortezomib, and lenalidomide and dexamethasone for VRD. But what we wanted to do in this study is to switch or to change the anti-CD38 or a PCMA antibody-drug conjugate belantamamab adoptin that has a multimodal model of action targeting both the plasma cell and the tumor cell and with some immunogenic effects or immune-related effects.

This was a trial that was a multi-cohort trial in which all patients received an induction therapy with 8 cycles of 3 weeks duration with belamaf and combination with VRd plus a maintenance phase with cycles with belamaf RV of 4 weeks duration. In the different cohorts, we evaluated different dosing schedules of starting doses of belamaf, 1.9[mg/kg], 1.4[mg/kg], or 1[mg/kg]. What was more important in this presentation is that we had evelumab in 3 cohorts. It was given once per cycle, day one of each cycle. In the second cohorts, other cohorts were once every other cycle, so one day every 6 weeks or 8 weeks. In the third part of the third cohorts, it was once every 3 cycles or every 9 weeks or every 12 weeks in the maintenance.

118 patients were included with a median age of 74 years. Many patients were older than 75 years old up to 88 in one case. The median duration of follow-up was quite variable between 15 and 4 years of follow-up for the different cohorts of patients. 

In terms of efficacy, what we saw is that there was high efficacy in all cohorts, 100%, 90% response rate, over 19% complete response rate, and MRD negativity rate also high. It was particularly high or good in patients receiving belamaf every cohort every month or patient receiving belamaf every other cycle. In this case, the response rate was 100%, 90% CR rate, and over 59% MRD negativity rate for these patients. There was higher response rate in those patients in this cohort, every other cycle that received the belamaf with a starting dose of 1.9 mg/kg – I think this is also quite striking. Here, the MRD activity rate reached almost 67% that they think it's remarkable. 

In terms of safety, the other important point here that we saw is that those patients that received belamaf every 30 cycles have a better safety profile. In this case, we focused on the corneal level adverse events. So 35% of these patients had grade 3/4 corneal dose events, lower than the other ones. Then that was all of them, particularly all of this resolved, this corneal event resolved. Probably a longer schedule or a longer administration of the belamaf is beneficial to improve the tolerability.

Finally, what was also very important is to see how the relative dose administered and the actual median dose intensity administered in the patients. We saw that at the beginning, in the induction, the dose, optimal dose in terms of relative dose and median dose was like every other cycle administration of belantamab. But in the maintenance phase, it was clear that patients could not tolerate every cycle and every other cycle, the relative dose intensity was low, and they could tolerate the belamaf given every 3 cycles. In this case, every 12 weeks, imagine what is 1 dose every 12 weeks. This was the tolerability in this case was much better and this was what we think is the best schedule for these patients.

In summary, we saw that this quadruple combination with belantamab is feasible in this patient population. It's highly effective for them we can use, but I think we can have to adapt the dose. It's probably more intense in the induction with higher doses and with belamaf given probably every other cycle every 2 months in this case. Then in the maintenance phase, we should skip and we should taper the dosing to give belamaf every 3 cycles and this improved tolerability. In fact, this is a schema we are now administering or using in other combinations that are being evaluated in patients with newly diagnosed myeloma, both eligible and in the non-transplant eligible patients such as the DREAMM-10 study.

With that, I want to thank all the people, all the investigators, all the patients, their families, and also GSK that was the sponsor of the study. Thank you very much.

Source:

Nadeem O, Santos DC, Magidson S, et al. DREAMM-9 final analysis: Belantamab mafodotin (belamaf), bortezomib, lenalidomide, and dexamethasone (BVRD) for trannsplantat-ineligible (TO) newly diagnosed multiple myeloma (NDMM). Presented at EHA Congress. June 11 - June 14, 2026. Stockholm, Sweden. Abstract EHA-2267.