Belantamab Mafodotin Monotherapy for Multiply-Relapsed Myeloma: A Retrospective Study From the United Kingdom and the Republic of Ireland

Abstract

Introduction: Belantamab mafodotin (belamaf) was the first BCMA-targeting immunotherapy licensed in myeloma and was available as monotherapy for a fifth or greater line of treatment. Outcomes for patients in the United Kingdom and the Republic of Ireland potentially differ from those of other regions and may illuminate factors predicting response to therapy.

Methods and results: We performed a retrospective study of patients treated with belamaf monotherapy in the United Kingdom and the Republic of Ireland. In our cohort of 88 patients, we saw an overall response rate (ORR) of 60%, a median progression-free survival (PFS) of 8.7 months and a median duration of response (DoR) of 15.8 months. The spectrum of adverse events was as expected, with 84% (71/85) of patients experiencing toxicity. Eye-related adverse events were the most common, affecting 66% (56/85), leading to dose reduction or delay in 41% (35/85) and discontinuation in 6% (5/85). We specifically assessed physician decision-making in the context of ocular side effects and found a relatively high frequency of the drug being administered despite moderate levels of toxicity.

Conclusion: Our cohort's ORR is significantly different from those of the DREAMM-2 and -3 trials and other real-world studies, though a long-duration response has been reported in other cohorts. Comparative analysis with other real-world studies did not reveal any significant factors predictive of ORR. The frequent administration of belamaf to patients with eye disease may well reflect a more pragmatic approach than was originally prescribed in the landmark trials.

Trial registration: The authors have confirmed clinical trial registration is not needed for this submission.

Keywords: BCMA; belantamab mafodotin; immunotherapy; keratopathy; real‐world.

FIGURE 1

Study format. (A) Completion rates of the various domains of the online data submission form for the 88 patients taken forward for analysis. Note that 10 of these responses were sent directly to the first author during manuscript preparation in the same format as the online form. (B) Distribution of cases across the UK and ROI, with relative n numbers indicated. (C) Histogram of the time intervals for the 33 cases where extended follow‐up data were obtained.

FIGURE 2

Drug exposure. (A) Summary of regimens at each line of therapy. (B) Drug exposure broken down by class.

FIGURE 3

Overall response. (A) Breakdown of overall response. (B) Forest plot for metaregression of ORRs across “real‐world” and DREAMM‐2 trials, showing heterogeneity of results with the current cohort outlying. (C) Subgroup analysis shows a lack of predictive factors by exact method, with the possible exception of ocular toxicity, though small numbers and confounding factors limit analysis. (D) Breakdown of drug exposure, as grouped by response. Cyclophosphamide at the first line was enriched in the responder group.

FIGURE 4

Survival data. (A) PFS and OS curves for the cohort. (B) Swimmer plot, indicating treatment status at last follow‐up. Note the lengthy DoR.

FIGURE 5

Ocular toxicity. (A) Breakdown of toxicities, categorised following the DREAMM‐2 analysis. (B) No obvious association between ocular toxicity and the distribution of response. (C) Trajectories of KVA grade over time where serial ophthalmological data is available. Each plot represents a patient. Purple trend line—KVA grade is stable/improves, and pink—KVA deteriorates. Each dot represents decision‐making at each assessment. Note five patients discontinued therapy. (D) Heatmap showing the presence or absence of four separate underlying ocular conditions has no bearing on the risk of developing one of the three ocular toxicities. Values represent the percent affected by keratopathy. KVA, keratopathy and visual acuity scale.