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).

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*

CBR, clinical benefit rate; CI, confidence interval; CR, complete response; DoR, duration of response; MR, minimal response; NA, not applicable; NR, not reached; OS, overall survival; PFS, progression-free survival; PR, partial response; sCR, stringent complete response; TTR, time to response; VGPR, very good PR. *Data from Nooka, et al.1 †CBR = sCR + CR + VGPR + PR + MR.
Secondary outcomes, months (95% CI; unless otherwise stated)	Belamaf 2.5 mg/kg (n = 97)	Belamaf 3.4 mg/kg (n = 99)	Belamaf lyophilized 3.4 mg/kg (n = 25)
CBR†, % (97.5% CI)	36.0 (26.6–46.5)	40.0 (30.7–50.7)	56.0 (34.9–75.6)
TTR	1.5 (1.0–2.1)	1.4 (0.9–2.1)	0.9 (0.8–2.3)
DoR	12.5 (4.2–19.3)	6.2 (4.8–18.7)	9.0 (2.8–10.4)
Median PFS	2.8 (1.6–3.6)	3.9 (2.0–5.8)	5.7 (2.2–9.7)
Median PFS in ≥VGPR	14.0 (9.7–NR)	16.8 (7.7–NR)	NA
Median OS	15.3 (9.9–18.9)	14.0 (10.0–18.1)	24.5 (8.7–NR)
Median OS in ≥VGPR	30.7 (19.7–37.9)	35.5 (14.1–NR)	NA
Median duration of treatment (range), weeks	9.3 (2.0–178.0)	12.0 (2.0–186.0)	16.6 (3.0–146.0)

Safety

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

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).

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.