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PACUPod is your trusted source for evidence-based insights tailored to advanced clinical pharmacists and physicians. Each episode dives into the latest primary literature, covering medication-focused studies across oncology, and many more. We break down study designs, highlight key findings, and objectively discuss clinical implications—without the hype—so you stay informed and ready to apply new evidence in practice. Whether you’re preparing for board certification or striving for excellence in patient care, PACUPod helps you make sense of the data, one study at a time.
Britany: Welcome back to PACULit, your go-to podcast for the latest clinical literature updates. Today, we’re diving into the updated overall survival data from the DREAMM-7 phase 3 trial, which evaluated belantamab mafodotin combined with bortezomib and dexamethasone in relapsed or refractory multiple myeloma. Seth, this is a hot topic given the unmet needs in RRMM. What’s your initial take?
Seth: Absolutely, Britany. Multiple myeloma remains incurable, and patients who relapse or become refractory after initial therapies, especially immunomodulatory drugs and proteasome inhibitors, face limited options. Targeting BCMA has been a promising strategy, and belantamab mafodotin, an anti-BCMA antibody-drug conjugate, has shown activity in heavily pretreated patients. But until now, we needed more robust data on survival benefits and optimal combinations.
Britany: Right, and that’s exactly what the DREAMM-7 trial aimed to address. It compared belantamab mafodotin plus bortezomib and dexamethasone—BVd—to the standard daratumumab, bortezomib, and dexamethasone regimen, or DVd. The study focused on progression-free survival as the primary endpoint but importantly provided mature overall survival data with a median follow-up of about 40 months.
Seth: The trial design was a global, randomized, open-label phase 3 study with 494 patients. Patients had relapsed or refractory multiple myeloma after at least one prior line of therapy, including those refractory to lenalidomide. They had to have adequate organ function and an ECOG performance status of two or less. Notably, patients with prior anti-BCMA therapy or significant ocular disease were excluded due to belantamab’s known ocular toxicity risks.
Britany: That’s a key point. The ocular toxicity, particularly keratopathy, has been a concern with belantamab mafodotin. The study’s exclusion of patients with significant pre-existing ocular disease was prudent. Also, the open-label design was balanced by an independent masked review committee for efficacy assessments, which helps reduce bias in outcome evaluation.
Seth: Exactly. Now, looking at the interventions, the experimental arm received belantamab mafodotin at 2.5 milligrams per kilogram intravenously every three weeks, combined with standard doses of bortezomib and dexamethasone. The comparator arm received daratumumab plus the same backbone. The primary endpoint was progression-free survival, but the updated analysis focused on overall survival, minimal residual disease negativity, duration of response, and safety.
Britany: And the results were quite compelling. The updated overall survival analysis demonstrated a significant improvement with BVd compared to DVd. The hazard ratio was 0.58, with a p-value of 0.0002, indicating a 42 percent reduction in the risk of death. Median overall survival was not reached in the BVd arm, while it was 34.5 months in the DVd arm.
Seth: That’s impressive. Moreover, the minimal residual disease negativity rate doubled with BVd—25 percent versus 10 percent in the DVd group. This suggests deeper responses with the belantamab combination. The median duration of response was also notably longer with BVd, at 40.8 months compared to 17.8 months with DVd.
Britany: These efficacy outcomes are clinically meaningful, especially considering the heavily pretreated population. However, safety is always a concern. The study reported higher rates of thrombocytopenia with BVd—56 percent versus 35 percent with DVd. But importantly, these hematologic toxicities were manageable with dose modifications and supportive care.
Seth: Right, and ocular adverse events were consistent with prior belantamab studies. Keratopathy occurred in about 40 percent of patients but was mostly low grade and reversible with treatment interruptions and dose adjustments. This highlights the importance of regular ophthalmologic monitoring during therapy.
Britany: Absolutely. From a clinical pearl perspective, this means pharmacists and clinicians should coordinate closely with eye care specialists and educate patients about symptoms like blurred vision or dry eyes. Early detection and management can prevent severe complications.
Seth: Another important consideration is drug interactions. Bortezomib is metabolized by cytochrome P450 enzymes, mainly CYP3A4, so concomitant use of strong inhibitors or inducers could affect its levels. Dexamethasone, a corticosteroid, also has multiple interactions, including with CYP3A4 substrates. Belantamab mafodotin, being an antibody-drug conjugate, has a different metabolism pathway but requires vigilance for overlapping toxicities.
Britany: Good point. Also, in special populations, such as patients with renal impairment, dose adjustments for bortezomib and dexamethasone may be necessary, but belantamab mafodotin dosing remains unchanged. The trial included patients with varying degrees of renal function, reflecting real-world applicability.
Seth: Speaking of real-world scenarios, the underrepresentation of Black patients in the trial is a limitation. Multiple myeloma disproportionately affects African American populations, so future studies should aim for more diverse enrollment to ensure generalizability.
Britany: Agreed. Now, placing these findings in context, the DREAMM-7 results build on earlier data from the same trial that showed progression-free survival benefits with BVd. Additionally, patient-reported outcomes favored BVd, with maintained or improved quality of life compared to DVd, which is crucial for this chronic disease.
Seth: Yes, and network meta-analyses have positioned belantamab-proteasome inhibitor combinations favorably against other regimens, especially in lenalidomide-exposed or refractory patients. This supports the growing role of belantamab-based triplets as a new standard of care in RRMM.
Britany: Furthermore, the DREAMM-8 trial validated belantamab’s efficacy when combined with pomalidomide and dexamethasone, reinforcing its versatility as a backbone agent. This expands options for patients who have progressed on multiple prior therapies.
Seth: Looking ahead, there are still unanswered questions. Long-term safety and cumulative toxicity of belantamab combinations need ongoing evaluation. Also, the optimal sequencing of belantamab relative to other BCMA-targeted therapies like CAR-T cells and bispecific antibodies remains to be defined.
Britany: Right, and direct head-to-head comparisons between different belantamab-based triplets, such as BVd versus belantamab-pomalidomide-dexamethasone, would be valuable to guide personalized treatment decisions.
Seth: Clinically, this means we should consider BVd for patients with RRMM after at least one prior therapy, especially those refractory to lenalidomide, while carefully monitoring for thrombocytopenia and ocular events. The manageable safety profile compared to T-cell redirecting therapies is an advantage.
Britany: To summarize, the DREAMM-7 updated overall survival analysis establishes belantamab mafodotin plus bortezomib and dexamethasone as a highly effective regimen that significantly improves survival and response durability in relapsed or refractory multiple myeloma. This supports its adoption as a new standard of care in this challenging patient population.
Seth: Absolutely, Britany. These findings represent a meaningful advance in MM treatment, offering hope for improved outcomes and quality of life. Staying current with such evolving evidence is essential for optimizing patient care.
Britany: Thanks for the insightful discussion, Seth. And to our listeners, be sure to review the full publication by Hungria and colleagues in Lancet Oncology for detailed data. We’ll keep tracking emerging literature to bring you the latest updates.
Seth: Looking forward to it. Until next time, stay curious and keep advancing clinical practice through evidence.
Britany: That wraps up today’s PACULit episode. Thanks for tuning in!