Extended follow-up from the DREAMM-2 trial

The potential of belantamab mafodotin (belamaf) in the relapsed or refractory (R/R) multiple myeloma (MM) setting was highlighted in 2019, when the pivotal DREAMM-2 study met its primary endpoint. The anti-B-cell maturation antigen (BCMA) antibody-drug conjugate demonstrated clinically meaningful overall response rates (ORRs), and in 2020 received approval from the U.S. Food and Drug Administration (FDA) and conditional marketing authorization from the European Commission.

Sagar Lonial and colleagues¹ recently published the results from a long-term analysis of the pivotal DREAMM-2 study (NCT03525678), evaluating single-agent belamaf for the treatment of patients with R/R MM who

• have received ≥3 lines of therapy;
• are refractory to an immunomodulatory agent and a proteasome inhibitor; and
• are refractory and/or intolerant to an anti-CD38 monoclonal antibody.

The Multiple Myeloma Hub is happy to present a summary of the 13-month follow-up of the DREAMM-2 study. Click here for a comprehensive overview of the clinical history of belamaf, the DREAMM-2 study design, and primary analysis efficacy and safety data. Why not also take a look at a summary of the DREAMM trials from the 2020 American Society of Clinical Oncology (ASCO) Annual Meeting, where data from the DREAMM-2 trial were considered practice changing.

Results

• Latest data cutoff: January 31, 2020.
• Patients remaining on the approved dose of belamaf, 2.5 mg/kg: 10%
• Responses and survival outcomes of patients enrolled to receive 2.5 mg/kg belamaf are outlined in Table 1.
• Among the 31 patients who achieved a partial response or better
  • 18 patients (58%) achieved a very good partial response or better
  • 7 patients achieved a stringent complete response or complete response
  • Median overall survival (OS): not reached (NR)
  • Median duration of response: 13.1 months (4.9 months–NR)
  • 1-year OS: 87% (69–95%)

Table 1. Patient responses to 2.5 mg/kg belamaf in the DREAMM-2 trial*

Belamaf, belantamab mafodotin; CBR, clinical benefit rate; CI, confidence interval; CR, complete response; DoR, duration of response; ITT, intention to treat; MR, minimal response; NR, not reached; ORR, overall response rate; OS, overall survival; PFS, progression-free survival; PR, partial response; sCR, stringent complete response; SD, stable disease; VGPR, very good partial response. *Data from Lonial S, et al.1 †Intention-to-treat population, 6% of patients could not be evaluated and were classed as non-responders.
Independent Review Committee-Assessed Best Response, %†	ITT population (N = 97)
ORR, % 97.5% CI	32 21.7–43.6
≥CR, %	7
VGPR, %	11
PR, %	13
MR, %	4
SD, %	28
CBR, % 95% CI	36 26.6–46.5
Median DoR, months 95% CI	11.0 4. 2–NR
Median OS, months 95% CI	13.7 9.9–NR
Median PFS, months 95% CI	2.8 1.6–3.6

• ORRs were comparable across patients with varying renal function and cytogenetic risk but were inferior in patients with extramedullary disease (Figure 1).
• No additional safety concerns were observed, and incidence was comparable between subgroups.
  • Treatment‐emergent adverse events (TEAEs): 88%
    • TEAEs Grade 3–4: 57%
  • Most common Grade ≥3 adverse events (AEs): keratopathy, thrombocytopenia, and anemia.
    • At data cutoff, 77% of patients with keratopathy had recovered.
  • Dose delays and reductions due to AEs (mainly due to keratopathy) were reported in 54% and 35% of patients, respectively. Of note, they had minimal impact on patient response.
    • 9% discontinued permanently due to AEs.

HR-cyto, high-risk cytogenetics, including 1q21 gain/amplification; HR-IMWG, high-risk cytogenetics according to International Myeloma Working Group criteria; ORR, overall response rate.
*Data from Lonial S, et al.¹

Conclusion

Data from the longer-term analysis highlight the durable clinical efficacy of belamaf in patients with heavily pretreated R/R MM. No additional safety concerns were associated with belamaf in this patient population.