Analysis of DREAMM-2 trial findings on patient-reported outcomes in relapsed/refractory multiple myeloma
Multiple myeloma, a cancer of plasma cells in the bone marrow, remains a formidable challenge in oncology. While new treatments have improved outcomes, the reality is that most patients eventually develop relapsed or refractory disease—meaning their cancer returns or stops responding to therapy. For those who have exhausted multiple treatment options, the prognosis is particularly grim, with limited alternatives available.
The DREAMM-2 clinical trial introduced a novel approach with belantamab mafodotin (belamaf), a first-in-class antibody-drug conjugate targeting B-cell maturation antigen (BCMA). While its efficacy against cancer cells was promising, what truly set this treatment apart was its dedicated focus on understanding how patients feel and function during treatment—a dimension captured through patient-reported outcomes (PROs) that are revolutionizing how we evaluate cancer therapies 1 6 .
Patient-reported outcomes are precisely what the name suggests: data collected directly from patients about their health status without interpretation by clinicians or researchers. These measures typically assess:
In multiple myeloma, where treatment is often continuous and aimed at controlling rather than curing the disease, understanding the patient experience is critical. PROs provide unique insights that traditional clinical measures cannot capture—how treatments actually affect people's lives beyond clinical settings.
This is especially valuable for evaluating therapies with unique side effect profiles, such as belamaf's ocular changes, which might be perceived very differently by patients than by their clinicians 1 .
Belantamab mafodotin represents a groundbreaking approach to multiple myeloma treatment. As an antibody-drug conjugate, it combines the targeting precision of monoclonal antibodies with the cancer-killing power of cytotoxic drugs.
B-cell maturation antigen is highly expressed on the surface of multiple myeloma cells but largely absent from other tissues, making it an ideal therapeutic target.
The antibody is conjugated to monomethyl auristatin F (MMAF), a potent toxin that disrupts microtubule function in cancer cells.
Beyond direct cell killing, belamaf stimulates immune-mediated responses through antibody-dependent cellular cytotoxicity and phagocytosis 6 .
This multimodal mechanism enables belamaf to effectively target resistant myeloma cells while potentially triggering broader anti-tumor immune responses.
The DREAMM-2 trial was a phase II, open-label, two-arm study conducted at multiple centers globally. It enrolled patients with triple-class refractory multiple myeloma—meaning their cancer had resisted three major classes of drugs: immunomodulatory agents, proteasome inhibitors, and anti-CD38 monoclonal antibodies.
These heavily pretreated patients had received a median of 7 prior therapies, representing a population with extremely limited options 3 5 .
Participants were randomized to receive either 2.5 mg/kg or 3.4 mg/kg of belamaf via intravenous infusion every three weeks until disease progression or unacceptable toxicity. The primary endpoint was overall response rate (ORR), while key secondary endpoints included progression-free survival, overall survival, safety, and—notably—patient-reported outcomes assessing quality of life and ocular symptoms 2 .
What set DREAMM-2 apart was its comprehensive approach to capturing the patient experience through multiple validated instruments:
A cancer-specific questionnaire assessing physical, role, emotional, cognitive, and social functioning, plus symptom scales and global health status.
A multiple myeloma-specific module evaluating disease symptoms, side effects, and future perspective.
A specialized instrument measuring eye-related symptoms and their impact on vision.
A 25-item tool assessing vision-targeted health status and visual functioning 1 .
These assessments were administered electronically at baseline, every 3-6 weeks during treatment, and at the end of treatment, ensuring consistent tracking of patients' experiences throughout their treatment journey.
The final analysis of DREAMM-2 demonstrated that belamaf delivered meaningful clinical benefits for these heavily pretreated patients. The overall response rate was 32% in the 2.5 mg/kg cohort, with 19% of patients achieving very good partial response or better.
Perhaps most impressively, the median duration of response was 12.5 months—remarkable for patients who had exhausted so many other options 2 .
For those who achieved deep responses, the benefits were even more substantial. Patients achieving very good partial response or better had a median progression-free survival of 14.0 months and overall survival of 30.7 months—exceptional outcomes for this advanced patient population 9 .
Despite the ocular side effects associated with belamaf, the PRO data revealed something surprising: patients maintained their overall health-related quality of life throughout treatment.
The EORTC QLQ-C30 data showed that core multiple myeloma symptoms—including fatigue and pain—remained stable or even improved during treatment. Similarly, overall quality of life and patient functioning were maintained even when patients experienced vision-related symptoms 1 .
This maintenance of quality of life was observed across multiple domains:
The PRO data provided nuanced insights into the ocular symptoms associated with belamaf:
| Symptom Metric | Time to Worst Severity (Days) | Time to Recovery (Days) | Impact on Activities |
|---|---|---|---|
| Blurred vision | 45 | 23.5 | Some reading limitations |
| Reduced BCVA* | 64 | 44.0 | Some driving limitations |
| Dry eye symptoms | 50 | 37.5 | Mild discomfort |
*BCVA = Best Corrected Visual Acuity 1
The data showed that while visual changes were common, they typically followed a predictable pattern: worsening within the first 1-2 months of treatment, followed by improvement even while continuing therapy. Importantly, these symptoms were generally transient and manageable, with median time to recovery ranging from 23.5 to 44.0 days depending on the specific symptom 1 3 .
The OSDI and NEI VFQ-25 questionnaires revealed that while some patients experienced limitations in visually demanding activities like driving and reading, these did not translate into broad reductions in overall quality of life. This distinction is crucial—while specific visual functions were affected, patients' global sense of well-being remained intact.
A key learning from DREAMM-2 was that proactive management of ocular events could mitigate their impact on patients:
Protocol-mandated ophthalmologic examinations before each dose
Treatment delays or reductions allowed for recovery
Artificial tears, corticosteroid eye drops, and avoidance of contact lenses
Notably, among patients who required dose delays exceeding 63 days due to ocular events, 88% maintained or deepened their response during this treatment hiatus—indicating that the immunological effects of belamaf may persist even during temporary treatment interruptions 3 5 .
| Assessment Scale | Baseline Score | Week 7 Score | Week 25 Score | Change from Baseline |
|---|---|---|---|---|
| EORTC QLQ-C30 Global Health | 58.2 | 60.1 | 59.8 | +1.6 |
| EORTC QLQ-C30 Physical Functioning | 65.4 | 66.8 | 67.2 | +1.8 |
| EORTC QLQ-C30 Fatigue | 42.1 | 38.9 | 39.3 | -2.8 |
| EORTC QLQ-C30 Pain | 39.8 | 35.2 | 34.7 | -5.1 |
| NEI VFQ-25 Composite | 89.6 | 82.3 | 85.4 | -4.2 |
Scores represent mean values on 0-100 scales. For EORTC scales, higher functioning/symptom scores represent better functioning/worse symptoms. For NEI VFQ-25, higher scores represent better visual functioning 1 .
The PRO data from DREAMM-2 offer several important insights for clinical practice:
While ocular side effects occur with belamaf, they must be weighed against both clinical efficacy and maintained overall quality of life.
The transient pattern of ocular symptoms suggests they can be managed through temporary dose modifications without compromising long-term clinical benefit.
Understanding the expected course of ocular symptoms helps clinicians prepare patients and set appropriate expectations.
Regular monitoring and early intervention can mitigate the impact of ocular events on patients' visual function.
These findings underscore why PRO measures are essential in comprehensive therapy evaluation—without them, we would have an incomplete picture of belamaf's true clinical value.
Based on the promising results from DREAMM-2, several follow-up studies are exploring belamaf in different settings:
These studies continue to incorporate PRO measures as key endpoints, recognizing that understanding the patient experience is essential for comprehensive treatment evaluation.
| Tool/Reagent | Type | Primary Function | Role in PRO Assessment |
|---|---|---|---|
| Belantamab mafodotin | Antibody-drug conjugate | BCMA-targeted therapy | Intervention being studied |
| EORTC QLQ-C30 | Validated questionnaire | Core cancer quality of life assessment | Measures overall health status and functioning |
| EORTC QLQ-MY20 | Validated questionnaire | Myeloma-specific symptoms and side effects | Assesses disease-specific concerns |
| OSDI | Specialized instrument | Ocular surface disease evaluation | Quantifies eye-related symptoms and impact |
| NEI VFQ-25 | Validated questionnaire | Vision-targeted health status | Measures visual functioning and its impact on daily activities |
The DREAMM-2 trial represents a significant advancement in how we evaluate cancer therapies—moving beyond traditional efficacy endpoints to incorporate the patient experience as a fundamental measure of treatment success. While belantamab mafodotin demonstrates meaningful clinical activity in heavily pretreated multiple myeloma patients, its true distinction lies in its preservation of quality of life despite predictable ocular side effects.
The PRO findings from DREAMM-2 offer valuable lessons for oncology drug development: symptomatic side effects must be understood in context of overall quality of life; transient side effects may be manageable without compromising efficacy; and patient-reported data provide essential insights that complement traditional clinical measures.
As we continue to develop new therapies for multiple myeloma and other cancers, the integration of PRO measures into clinical trials ensures that we never lose sight of what matters most: helping patients live both longer and better lives. The story of belamaf reminds us that true therapeutic success is measured not just in response rates and survival statistics, but in preserving the quality of life and dignity of those we treat.