DREAMM-2: Long-term analysis of efficacy and safety of belamaf in patients with RRMM

Despite advances in the treatment of multiple myeloma (MM), outcomes remain poor, particularly in patients with relapsed/refractory (R/R) MM. Bispecific T-cell engager monoclonal antibodies and chimeric antigen receptor (CAR) T-cell therapies have provided patients with RRMM more treatment options; however, they can be difficult to administer and are associated with considerable adverse effects. In the primary analysis and extended follow-up of the DREAMM2 trial (NCT03525678), assessing the efficacy and safety of the first-in-class B-cell maturation antigen-binding antibody (BCMA)-drug conjugate belantamab mafodotin (belamaf), durable responses were observed in heavily pretreated patients with RRMM.

Recently, Nooka et al.¹ published the final analysis of the DREAMM-2 trial in Cancer. The Multiple Myeloma Hub is pleased to summarize the key findings here.

Study design

DREAMM-2 is a phase II open-label study of belamaf in patients with RRMM who had received ≥3 prior therapies. The study design and patient characteristics have previously been reported on the Multiple Myeloma Hub. For long-term follow-up, an additional independent cohort treated with 3.4 mg/kg of a belamaf lyophilized formulation was also included.

• The primary endpoint was overall response rate
• Secondary endpoints included clinical benefit rate, time-to-response, duration of response, progression-free survival, overall survival, adverse events (AEs), and ocular events
• Health-related quality of life, disease-related symptoms, and impact on functioning were also evaluated

Results

The intention-to-treat population comprised 97, 99, and 25 patients in the belamaf 2.5 mg/kg, 3.4 mg/kg, and belamaf lyophilized cohort, respectively. The data cut-off was March 31, 2022.

Efficacy

• The median follow-up was 12.5 months (range, 0.1–40.4 months), 13.8 months (range, 0.1–42.8 months), and 24.5 months (range, 1.8–38.8 months) in the 2.5 mg/kg, 3.4 mg/kg, and lyophilized cohort, respectively.
• The overall response rate was 32%, 35%, and 52% in the 2.5 mg/kg, 3.4 mg/kg, and lyophilized cohort, respectively (Figure 1).

Figure 1. Response rates* 

CR, complete response; MR, minimal response; ORR, overall response rate; PR, partial response; sCR, stringent complete response; SD, stable disease; VGPR, very good PR.
*Data from Nooka, et al.¹

 The secondary outcomes are summarized in Table 1.

Table 1. Secondary endpoints*

Safety

Rates of AEs and serious AEs (SAEs) are shown in Figure 2.

Figure 2. Adverse events* 

AEs, adverse events; SAEs, serious AEs; TRAEs, treatment-related AEs.
*Data from Nooka, et al.^1
†AEs occurring in ≥15% of patients in the 2.5 mg/kg and 3.4 mg/kg cohorts.
^‡In the 2.5 mg/kg, 3.4 mg/kg, and lyophilized cohorts, 1% (sepsis), 2% (1 cerebral hemorrhage, 1 hemophagocytic lymphohistiocytosis), and 0% of AEs were considered treatment related, respectively.

 The most frequently reported Grade 3–4 AEs included keratopathy, thrombocytopenia, and anemia (Figure 3).

Figure 3. Grade 3–4 AEs* 

AEs, adverse events.
*Data from Nooka, et al.^1
†Includes keratitis, ulcerative keratitis, infective keratitis, limbal stem cell deficiency, and punctate keratitis.
^‡Includes neutropenia, febrile neutropenia, and decreased neutrophil count.

• The most frequently occurring ocular events in in the 2.5 mg/kg, 3.4 mg/kg, and lyophilized cohort, respectively, included:
  • keratopathy (71%, 75%, 96%);
  • blurred vision (25%, 36%, 42%);
  • best corrected visual acuity reduced to 20/50 or worse (48%, 49% 75%); and
  • dry eye (18%, 25%, 25%).

Patient reported outcomes

• Patients in both 2.5 and 3.4 mg/kg cohorts reported durable global health status and quality of life.
• By Week 7, there was an improvement in both fatigue and pain scores as well as disease symptoms.
• Worsening of 12.5 points in Ocular Surface Disease Index vision-related functioning was reported in 51%, 62%, and 75% of patients in the 2.5 mg/kg, 3.4 mg/kg, and lyophilized cohort, respectively.

Conclusion

The long-term analysis of the DREAMM-2 trial demonstrated deep and durable responses with belamaf at 2.5 or 3.4 mg/kg in patients with triple-class RRMM; the safety profile was also manageable. These findings are comparable with real-world studies on the benefits of belamaf and will continue to inform future studies.