Single-agent Belantamab Mafodotin Research Articles

Real-world efficacy of single-agent belantamab mafodotin in relapsed systemic AL amyloidosis.

Systemic light chain (AL) amyloidosis is a relapsing plasma cell disorder. Therapy is limited, particularly for triple-class refractory disease. We report the use of belantamab mafodotin, a BCMA-directed drug-antibody conjugate, for relapsed AL amyloidosis, including patients traditionally excluded from clinical trials. Thirty-one patients were reviewed, with a median of three prior lines of therapy. The median follow-up was 12 months (95% CI 4-19), and a median of five doses were delivered. The best haematological overall response rate was 71%, and the complete/very good partial response was 58%. Sixty-eight percent had keratopathy and improved in all. Belantamab mafodotin has high efficacy and good tolerability in patients with relapsed AL amyloidosis.

Impact of Long-Term Treatment with Belantamab Mafodotin on Safety and Efficacy Outcomes in Patients with Relapsed/Refractory Multiple Myeloma in DREAMM-3

Introduction: DREAMM-3 (NCT04162210) is a randomized study comparing single-agent belantamab mafodotin, a first-in-class antibody-drug conjugate targeting B-cell maturation antigen, to a standard-of-care regimen, pomalidomide plus dexamethasone (Pd). This post-hoc analysis from the DREAMM-3 trial evaluated the safety and efficacy of long-term treatment (≥52 weeks) with belantamab mafodotin compared with Pd, as well as the effects of dose modifications, in adult patients with relapsed/refractory multiple myeloma (RRMM) at third line of therapy or later. Methods: Patients were randomized (2:1) to belantamab mafodotin 2.5 mg/kg intravenously once every 3 weeks (Q3W; 21-day cycle) or pomalidomide 4 mg orally once daily (Days 1-21) and dexamethasone 40 mg (20 mg if >75 years) orally once weekly (28-day cycle). Belantamab mafodotin dose reductions or delays were permitted to manage treatment-related Grade 3-4 adverse events (AEs), or Grade 2 AEs that were worsening or had symptoms lasting >7 days. Following AE resolution to Grade ≤1, belantamab mafodotin treatment could resume with or without dose reduction (to 1.9 mg/kg). If no dose delays occurred, patients could receive a maximum of 17 cycles in 52 weeks, hence 17 cycles was used as a threshold to assess long term safety. Ocular exams were performed prior to dosing belantamab mafodotin Q3W up to Cycle 6, then every 3 months if no significant ocular events were reported. Treatment-related ocular AEs were graded per National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5 and per the Keratopathy Visual Acuity (KVA) scale. The KVA scale incorporates corneal examination findings and changes in Snellen-equivalent best corrected visual acuity (BCVA) into a composite grade. Ocular AEs are reported as worst-case post-baseline. Efficacy responses (per 2016 International Myeloma Working Group criteria) were assessed Q3W, regardless of treatment delays. Results: As of September 12, 2022, 50/218 (23%) patients were treated with belantamab mafodotin for ≥52 weeks. AEs were reported in all patients treated with belantamab mafodotin for ≥52 weeks. Grade ≥3 AEs occurred in 82% (n=41); the most frequent were reduced visual acuity (24%), thrombocytopenia (18%), and neutropenia (16%). The majority of AEs reported occurred at or before cycle 17. For the most common (>40%) AEs (any grade), few additional events occurred after cycle 17 (1 new occurrence each of dry eye, reduced visual acuity, eye irritation, and thrombocytopenia after cycle 17). Few infections (any grade) occurred after cycle 17 (COVID-19, n=5; viral infection, n=1; pneumonia influenzal, n=1). No patients permanently discontinued treatment due to AEs considered related to belantamab mafodotin. Ocular AEs were reported in 94% (n=47) of patients treated with belantamab mafodotin for ≥52 weeks. The majority of ocular AEs (n=487) were of Grade 1 or 2 severity (88%) and no ocular AEs led to study treatment discontinuation. At the time of data cutoff, 95% (n=41) of patients experiencing Grade ≥2 KVA events had recovered prior to the end of study treatment exposure (defined as last dose + 20 days). Most patients had a dose modification, and no loss of efficacy was observed. The clinical benefit rate (≥minimal response) in these patients was 90% (45/50) and the median time to best response was 6.3 months (range 0.8-18.8). Median duration of response was not reached (NR; 95% CI 17.9, NR) in the subset of patients treated for ≥52 weeks. At the time of data cutoff, 94% (n=47) patients were alive. Conclusions: In patients who received long-term treatment (≥52 weeks), the safety profile of belantamab mafodotin was consistent with previous reports. Despite the need for belantamab mafodotin dose delays and reductions, no patients discontinued study treatment due to belantamab mafodotin-related AEs. During dose delays, clinical responses were maintained or deepened in most cases, demonstrating that management of AEs using dose modifications did not impact clinical activity. Together, this suggests that dose modifications are highly effective in the management of emerging AEs while allowing for sustained clinical benefit. Funding: GSK (207495). Drug linker technology licensed from Seagen Inc.; monoclonal antibody produced using POTELLIGENT Technology licensed from BioWa.

Treatment with low-dose, single-agent belantamab mafodotin is safe and provides long-term responses in heavily pretreated multiple myeloma patients.

To evaluate whether low-dose belantamab mafodotin (B-MAF) dosing results in lower toxicity and better overall outcome. We retrospectively evaluated nine consecutive patients treated with low-dose (1.9 mg/kg) B-MAF. The median age was 70 years. Most patients were penta-refractory. Ocular toxicity was observed in 77.7%. Adverse events resulting in treatment delays were recorded in 9 out of 124 cycles being given. Overall response rate was 66% (6/9), and all responding patients achieved very good partial response or better. Within a median follow-up of 12 (range 0.5-13.8) months, median progression-free survival and overall survival were 14 (CI95% 6-22) and 20 (95%CI 0-41) months, respectively. Low-dose B-MAF regimen showed high-efficacy and low-toxicity profile.

Efficacy and safety of single-agent belantamab mafodotin versus pomalidomide plus low-dose dexamethasone in patients with relapsed or refractory multiple myeloma (DREAMM-3): a phase 3, open-label, randomised study

Multiple myeloma remains incurable, and heavily pretreated patients with relapsed or refractory disease have few good treatment options. Belantamab mafodotin showed promising results in a phase 2 study of patients with relapsed or refractory multiple myeloma at second or later relapse and a manageable adverse event profile. We aimed to assess the safety and efficacy of belantamab mafodotin in a phase 3 setting. In the DREAMM-3 open-label phase 3 study, conducted at 108 sites across 18 countries, adult patients were enrolled who had confirmed multiple myeloma (International Myeloma Working Group criteria), ECOG performance status of 0-2, had received two or more previous lines of therapy, including two or more consecutive cycles of both lenalidomide and a proteasome inhibitor, and progressed on, or within, 60 days of completion of the previous treatment. Participants were randomly allocated using a central interactive response technology system (2:1) to receive belantamab mafodotin 2·5 mg/kg intravenously every 21 days, or oral pomalidomide 4·0 mg daily (days 1-21) and dexamethasone 40·0 mg (20·0 mg if >75 years) weekly in a 28-day cycle. Randomisation was stratified by previous anti-CD38 therapy, International Staging System stage, and number of previous therapies. The primary endpoint was progression-free survival in all patients who were randomly allocated. The safety population included all randomly allocated patients who received one or more doses of study treatment. This trial is registered with ClinicalTrials.gov, NCT04162210, and is ongoing. Data cutoff for this analysis was Sept 12, 2022. Patients were recruited between April 2, 2020, and April 18, 2022. As of September, 2022, 325 patients were randomly allocated (218 to the belantamab mafodotin group and 107 to the pomalidomide-dexamethasone group); 184 (57%) of 325 were male and 141 (43%) of 325 were female, 246 (78%) of 316 were White. Median age was 68 years (IQR 60-74). Median follow-up was 11·5 months (5·5-17·6) for belantamab mafodotin and 10·8 months (5·6-17·1) for pomalidomide-dexamethasone. Median progression-free survival was 11·2 months (95% CI 6·4-14·5) for belantamab mafodotin and 7·0 months (4·6-10·6) for pomalidomide-dexamethasone (hazard ratio 1·03 [0·72-1·47]; p=0·56). Most common grade 3-4 adverse events were thrombocytopenia (49 [23%] of 217) and anaemia (35 [16%]) for belantamab mafodotin, and neutropenia (34 [33%] of 102) and anaemia (18[18%]) for pomalidomide-dexamethasone. Serious adverse events occurred in 94 (43%) of 217 and 40 (39%) of 102 patients, respectively. There were no treatment-related deaths in the belantamab mafodotin group and one (1%) in the pomalidomide-dexamethasone group due to sepsis. Belantamab mafodotin was not associated with statistically improved progression-free survival compared with standard-of-care, but there were no new safety signals associated with its use. Belantamab mafodotin is being tested in combination regimens for relapsed or refractory multiple myeloma. GSK (study number 207495).

Patient-Reported Outcomes With Belantamab Mafodotin Treatment in Patients With Triple-Class Refractory Multiple Myeloma.

In the randomized phase II DREAMM-2 study, single-agent belantamab mafodotin demonstrated deep and durable responses and a manageable safety profile in triple-class refractory relapsed/refractory multiple myeloma (RRMM). We present patient-reported outcomes (PROs) from this study for patients treated with the approved dose of belantamab mafodotin (2.5 mg/kg q3w). Disease and treatment-related symptoms, health-related quality of life (HRQOL), functioning, and patient-reported ocular changes were assessed using questionnaires (European Organisation for Research and Treatment of Cancer Quality of Life questionnaires EORTC-QLQ-C30 and EORTC-QLQ-MY20, Ocular Surface Disease Index [OSDI], and the National Eye Institute Visual Functioning Questionnaire 25 [NEI VFQ-25]) at baseline, during treatment (every 3 or 6 weeks), and at the end of treatment (EOT). Eye examinations were conducted at baseline, prior to each treatment cycle, and at EOT. Patients reported ocular symptoms in the OSDI and NEI VFQ-25 questionnaires, with the median time to worst severity of 45 to 64 days depending on symptoms considered. Some limitations in driving and reading were reported. Ocular symptoms were improved and median time to recovery was 23.5 to 44.0 days. EORTC-QLQ-C30 data suggest core MM symptoms (including fatigue and pain), overall HRQOL, and patient functioning were maintained while patients continued belantamab mafodotin treatment, even if meaningful worsening of vision-related symptoms occurred. These PRO results, together with the clinical efficacy of belantamab mafodotin, support its use in patients with RRMM and further evaluation of its use at earlier lines of therapy.

A Phase 1/2, Dose and Schedule Evaluation Study to Investigate the Safety and Clinical Activity of Belantamab Mafodotin Administered in Combination with Lenalidomide and Dexamethasone in Transplant-Ineligible Patients with Newly Diagnosed Multiple Myeloma

Introduction Lenalidomide and dexamethasone (Rd) treatment is common for transplant ineligible (TI) patients (pts) with newly diagnosed multiple myeloma (NDMM). Addition of a third antimyeloma agent with a different mode of action than lenalidomide (e.g., proteasome inhibitors or anti-CD38 monoclonal antibodies) leads to higher response rates and deeper responses. Single-agent belantamab mafodotin (belamaf), an antibody-drug conjugate directed against B-cell maturation antigen, has shown a clinically meaningful antimyeloma activity with a manageable safety profile in double/triple class exposed pts with relapsed or refractory multiple myeloma. Preclinical data demonstrate synergy between belamaf and lenalidomide, suggesting added benefit in the combination of belamaf plus Rd. We report on the safety and efficacy of upfront belamaf plus Rd in TI pts with NDMM. Methods The ongoing, prospective, open-label, 2-part, phase 1/2 BelaRd study (NCT04808037) aims to enroll 66 pts with TI NDMM from a Greek center. Eligible are adult pts with an Eastern Cooperative Oncology Group status 0-2 and adequate organ function. In Part 1, 18 pts are randomized (1:1:1) in 3 cohorts to receive belamaf 2.5, 1.9, or 1.4 mg/kg doses by intravenous infusion once every 8 weeks (Q8W) plus Rd and the safety/tolerability of the combination is evaluated for pts with ≥4 weeks of follow up. As safety review found no unexpected findings, an additional 6 pts were enrolled in each dose cohort to select the belamaf recommended phase 2 dose (RP2D). Part 2 (dose expansion; not initiated as yet) will further evaluate the safety and preliminary clinical activity of belamaf RP2D Q8W plus Rd in 30 additional pts. This descriptive analysis presents the safety and efficacy data for all Part 1 pts (data cut-off: 24 June 2022). Results Thirty-six pts (median age: 72.5 years [range 64.0-86.0]; male: 19 (52.8%) were included in this analysis. By data cut-off, 31 (86.1%) were still on treatment and 5 (13.9%) pts had discontinued (death due to a belamaf-unrelated adverse event [AE]: 4 [11.1%]; consent withdrawal: 1 [2.8%]). At baseline, most (27, 75.0%) pts were at Revised International Staging System stage II, and 3 (8.3%) pts had high-risk cytogenetics (i.e., del(17p13), t(4;14), t[14;16]). At a median follow up of 9.5 months (range 3.2-15.4), a median of 4.0 (range 2.0-8.0) belamaf infusions were administered and the median number of cycles reached was 10.0 (range 3.0-16.0). Thirty-one (86.1%) pts experienced ≥1 grade (Gr) ≥3 treatment-emergent AEs (TEAEs). Most common (≥ 10.0% of pts) Gr ≥3 TEAEs were fatigue (16 pts, 44.4%), visual acuity reduced (12 pts, 33.3%), rash (6 pts, 16.7%), and COVID-19 infection (4 pts, 11.1%); Gr 3-4 thrombocytopenias were not reported, nor were any Gr infusion-related reactions. Pts with Gr 1-2 ocular symptoms, visual acuity reduced, and keratopathy were 34 (94.4%), 22 (61.1%), and 28 (77.8%), respectively; pts with Gr 3 ocular symptoms, visual acuity reduced, and keratopathy were 1 (2.8%), 12 (33.3%), and 0 (0.0%), respectively; no Gr 4 events occurred (Table). The overall response rate (partial response [PR] or better) was 97.2% (35 pts; stringent complete response: 8.3% [3 pts]; complete response: 11.1% [4 pts]; very good partial response: 52.8% [19 pts]; partial response: 25.0% [9 pts]); no disease progression was reported. Median time to first response was 1.0 months (range 0.9-6.0). RP2D was 1.9 mg/kg, as in this dose Gr ≥ 3 ocular TEAE and difficulties in activities of daily living 'most of the time' were observed in only 1 (8.3%) pt each at the time of the RP2D analysis, concurrently with a high ORR (91.7%). Conclusions Part 1 of the BelaRd study showed that, in TI pts with NDMM, the safety profile of belamaf Q8W plus Rd was manageable. The belamaf Rd combination induced rapid and deep hematological responses, with almost all (97.2%) pts achieving at least PR and first response observed at a median of 1.0 months. The selected belamaf RP2D dose was 1.9 mg/kg. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Exploring alternative dosing regimens of single-agent belantamab mafodotin on safety and efficacy in patients with relapsed or refractory multiple myeloma: DREAMM-14.

TPS8073 Background: Belantamab mafodotin (belamaf: BLENREP) is a first-in-class, monomethyl auristatin F (MMAF)-containing, B-cell maturation antigen (BCMA)-directed antibody–drug conjugate (ADC). In the DREAMM-2 study, belamaf showed deep responses with a manageable safety profile in patients with relapsed/refractory multiple myeloma (RRMM). At 13 months of follow-up, the median duration of response was 11 months and overall survival was 13.7 months at the 2.5 mg/kg Q3W dose. Corneal events are common and expected with belamaf and other MMAF-containing ADCs. In DREAMM-2, corneal events were managed with dose modifications. Clinical responses were observed even with prolonged dose holds, suggesting alternative dosing regimens may lower corneal event rates without compromising efficacy. The DREAMM-14 study (NCT05064358) will investigate if an improved benefit/risk profile of single-agent belamaf can be achieved by modifying the dose, schedule, or both, relative to the approved dosing regimen (2.5 mg/kg Q3W). Methods: This Phase II, randomized, open-label study will include adults with RRMM who had ≥3 prior lines of therapy (LOT), including an anti-CD38 monoclonal antibody, an immunomodulatory agent, and a proteasome inhibitor. Patients with corneal epithelial disease (except nonconfluent superficial punctate keratitis) or with prior exposure to BCMA-targeted therapies, or ADCs will be excluded. Patients will be randomized into Arms A–D (n=40 each) and Arm E (n=20) in parallel and stratified by the International Staging System (I vs II vs III) and prior LOT (3 vs ≥4). Belamaf will be administered as follows—Arm A: 2.5 mg/kg Q3W; Arm B: 1.9 mg/kg Q3W; Arm C: 2.5 mg/kg Q6W; Arm D: 1.9 mg/kg Q6W; Arm E: 1.9 mg/kg Q6W with ocular event-related dose modifications based on oncology staff assessment of ocular symptoms (patient-reported symptoms using the Ocular Surface Disease Index), and visual acuity (Snellen chart or equivalent) in addition to corneal findings assessed by an eye care specialist. Patients in all Arms will have response assessments, safety assessments, and ophthalmic exams performed by an eye care specialist Q3W regardless of dosing schedule. Ocular event-related dose modifications (except in Arm E) will be guided by a modified Keratopathy and Visual Acuity scale. The primary endpoint will be incidence of ocular events. Key secondary endpoints include ocular safety and tolerability, overall safety and tolerability, pharmacokinetics, and efficacy outcomes. Follow-up for progression-free survival will be Q3W until progressive disease, start of new anticancer therapy, withdrawal of consent, end of study, or death. Status: Recruitment is ongoing. Funding: GSK (Study 209628); drug linker technology licensed from Seagen Inc.; mAb produced using POTELLIGENT Technology licensed from BioWa. Clinical trial information: NCT05064358.

Exploring Alternative Dosing Regimens of Single-Agent Belantamab Mafodotin on Safety and Efficacy in Patients with Relapsed or Refractory Multiple Myeloma: DREAMM-14

Exploring Alternative Dosing Regimens of Single-Agent Belantamab Mafodotin on Safety and Efficacy in Patients with Relapsed or Refractory Multiple Myeloma: DREAMM-14

DREAMM-5 Study: Investigating the Synergetic Effects of Belantamab Mafodotin Plus Inducible T-Cell Co-Stimulator Agonist (aICOS) Combination Therapy in Patients with Relapsed/Refractory Multiple Myeloma

DREAMM-5 Study: Investigating the Synergetic Effects of Belantamab Mafodotin Plus Inducible T-Cell Co-Stimulator Agonist (aICOS) Combination Therapy in Patients with Relapsed/Refractory Multiple Myeloma

DREAMM-2: Indirect Comparisons of Belantamab Mafodotin vs. Selinexor + Dexamethasone and Standard of Care Treatments in Relapsed/Refractory Multiple Myeloma

IntroductionSingle-agent belantamab mafodotin (belamaf; BLENREP) demonstrated deep and durable responses in patients with relapsed/refractory multiple myeloma and ≥ 3 prior lines of therapy, including an immunomodulatory agent, proteasome inhibitor, and anti-CD38 antibody (DREAMM-2; NCT03525678).MethodsAt the time of this study, STORM Part 2, NCT02336815 (selinexor plus low-dose dexamethasone; sel + dex) was systematically identified as the only feasible comparator to the DREAMM-2 cohort. Matching-adjusted indirect comparisons (MAIC) evaluated efficacy and safety of belamaf (2.5 mg/kg; n = 97) versus sel + dex (80 mg + 20 mg, respectively; n = 123). Populations were weighted for clinically validated effect modifiers and prognostic factors. Outcomes included overall survival (OS), progression-free survival (PFS), duration of response (DoR), overall response rate (ORR), time to response (TTR), and safety. The relative efficacy of belamaf versus standard of care (SoC) on OS was estimated by a Bucher indirect treatment comparison using the MAIC-adjusted hazard ratios (HR) for OS of belamaf (DREAMM-2) versus sel + dex (STORM Part 2) and a HR adjusted for refractoriness to carfilzomib and high-risk cytogenetics of sel + dex (STORM) versus SoC (MAMMOTH).ResultsBelamaf demonstrated improved OS (HR 0.53; 95% confidence interval 0.34, 0.83; p = 0.005) and DoR (0.41; 0.21, 0.83; p = 0.013) versus sel + dex. There were no statistically significant differences in ORR, TTR, and PFS. Belamaf had a favorable safety profile for most evaluable hematologic (any-grade, Grade 3–4) and non-hematologic (any-grade) adverse events versus sel + dex. Significantly improved OS was observed with belamaf versus SoC (0.29; 0.16, 0.54; p < 0.001).ConclusionSingle-agent belamaf represents a new treatment option for triple-class refractory patients with RRMM.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12325-021-01884-7.

Longer term outcomes with single-agent belantamab mafodotin in patients with relapsed or refractory multiple myeloma: 13-month follow-up from the pivotal DREAMM-2 study.

BackgroundOn the basis of the DREAMM‐2 study (ClinicalTrials.gov identifier NCT03525678), single‐agent belantamab mafodotin (belamaf) was approved for patients with relapsed or refractory multiple myeloma (RRMM) who received ≥4 prior therapies, including anti‐CD38 therapy. The authors investigated longer term efficacy and safety outcomes in DREAMM‐2 after 13 months of follow‐up among patients who received belamaf 2.5 mg/kg.MethodsDREAMM‐2 is an ongoing, phase 2, open‐label, 2‐arm study investigating belamaf (2.5 or 3.4 mg/kg) in patients with RRMM who had disease progression after ≥3 lines of therapy and were refractory to immunomodulatory drugs and proteasome inhibitors and refractory and/or intolerant to an anti‐CD38 therapy. The primary outcome was the proportion of patients that achieved an overall response, assessed by an independent review committee.ResultsAs of January 31, 2020, 10% of patients still received belamaf 2.5 mg/kg. Thirty‐one of 97 patients (32%; 97.5% confidence interval [CI], 21.7%‐43.6%) achieved an overall response, and 18 responders achieved a very good partial response or better. Median estimated duration of response, overall survival, and progression‐free survival were 11.0 months (95% CI, 4.2 months to not reached), 13.7 months (95% CI, 9.9 months to not reached), and 2.8 months (95% CI, 1.6‐3.6 months), respectively. Response and survival outcomes in patients who had high‐risk cytogenetics or renal impairment were consistent with outcomes in the overall population. Outcomes were poorer in patients with extramedullary disease. In patients who had a clinical response and prolonged dose delays (>63 days; mainly because of corneal events), 88% maintained or deepened responses during their first prolonged dose delay. Overall, there were no new safety signals during this follow‐up.ConclusionsExtended follow‐up confirms sustained clinical activity without new safety signals with belamaf in this heavily pretreated patient population with RRMM.

Landscape review of the patient-reported outcomes version of the common terminology criteria for adverse events (PRO-CTCAE) in oncology: Adoption and recent learnings.

e18587 Background: The PRO-CTCAE is a patient-reported outcome measure of symptomatic toxicity in oncology trials designed to complement CTCAE criteria (clinician’s measure of adverse events [AEs]). Items for evaluation are selected from 78 symptomatic toxicities in the CTCAE. PRO-CTCAE uptake and use has not been uniformly assessed; understanding how to best analyze and present PRO-CTCAE data is important. We reviewed literature on clinical trials reporting the PRO-CTCAE to ascertain its use and current analytical methods to inform future analyses. Methods: A review of the literature and ongoing oncology trials using PubMed, oncology and outcomes research conferences (ASCO, ASH, ISOQOL, ISPOR), and ClinicalTrials.gov was completed August 2019; updated November 2020. Selected literature included guidance on: item selection; analytical methods; PRO-CTCAE data/endpoint use in clinical trials. Analytical and visualization methods from the literature were used to inform the specification of PRO-CTCAE analyses conducted on data from the DREAMM-2 (NCT03525678) trial of single-agent belantamab mafodotin (belamaf; BLENREP), a B-cell maturation antigen–binding antibody–drug conjugate, in relapsed/refractory multiple myeloma. Results: After screening (n = 197), 45 articles were reviewed: 13 related to recommendations for use/analysis, 7 to item selection, and 25 to examples of PRO-CTCAE use. 118 completed/ongoing trials reported PRO-CTCAE use (17 [14%] Phase I or I/II; 73 [62%] Phase II, II/III, or III; 3 [3%] Phase IV; 25 had no phase reported). Most (92/118, 78%) trials included the PRO-CTCAE as a secondary endpoint. The number of trials using the PRO-CTCAE increased from 3 in 2015 to 30 in 2020. PRO-CTCAE data in the literature were reported descriptively using tables (maximum post-baseline ratings; mean change over time; ratings higher than a predefined cutoff) and graphs (line graphs; stacked bar charts; heatmaps). These and more sophisticated analyses were applied to DREAMM-2 data to best capture the dynamics of patient-reported AEs over time, or control for baseline PRO-CTCAE ratings (eg, Toxicity over Time approach; ordinal log-linear models). Conclusions: The importance of tolerability and symptomatic AEs for patients is increasingly recognized, particularly for new therapies. This landscape review demonstrates recent growth in interest and adoption of PRO-CTCAE. There are few existing standards for analysis; this research increases understanding of existing methods and further evaluates ways of analyzing and presenting PRO-CTCAE data over time. Additional research exploring innovative methods to analyze PRO-CTCAE data and address its challenges is needed. Funding Source: GlaxoSmithKline (212225). Drug linker technology licensed from Seagen Inc.; mAb produced using POTELLIGENT Technology licensed from BioWa.

PCN309 Methodology for Evaluating Meaningful Change Thresholds in Patient-Reported Outcome (PRO) Measures for Corneal Events in Patients with Relapsed/Refractory Multiple Myeloma (RRMM) Receiving Single-Agent Belantamab Mafodotin (BELAMAF)

PCN309 Methodology for Evaluating Meaningful Change Thresholds in Patient-Reported Outcome (PRO) Measures for Corneal Events in Patients with Relapsed/Refractory Multiple Myeloma (RRMM) Receiving Single-Agent Belantamab Mafodotin (BELAMAF)

Recovery of Ocular Events with Longer-Term Follow-up in the DREAMMM-2 Study of Single-Agent Belantamab Mafodotin (Belamaf) in Patients with Relapsed or Refractory Multiple Myeloma (RRMM)

Recovery of Ocular Events with Longer-Term Follow-up in the DREAMMM-2 Study of Single-Agent Belantamab Mafodotin (Belamaf) in Patients with Relapsed or Refractory Multiple Myeloma (RRMM)

Single-agent belantamab mafodotin for relapsed/refractory multiple myeloma: analysis of the lyophilised presentation cohort from the pivotal DREAMM-2 study

DREAMM-2 (NCT03525678) is an ongoing global, open-label, phase 2 study of single-agent belantamab mafodotin (belamaf; GSK2857916), a B-cell maturation antigen-targeting antibody-drug conjugate, in a frozen-liquid presentation in patients with relapsed/refractory multiple myeloma (RRMM). Alongside the main study, following identical inclusion/exclusion criteria, a separate patient cohort was enrolled to receive belamaf in a lyophilised presentation (3.4 mg/kg, every 3 weeks) until disease progression/unacceptable toxicity. Primary outcome was independent review committee-assessed overall response rate (ORR). Twenty-five patients were enrolled; 24 received ≥1 dose of belamaf. As of 31 January 2020, ORR was 52% (95% CI: 31.3–72.2); 24% of patients achieved very good partial response. Median duration of response was 9.0 months (2.8–not reached [NR]); median progression-free survival was 5.7 months (2.2–9.7); median overall survival was not reached (8.7 months–NR). Most common grade 3/4 adverse events were keratopathy (microcyst-like corneal epithelial changes, a pathological finding seen on eye examination [75%]), thrombocytopenia (21%), anaemia (17%), hypercalcaemia and hypophosphatemia (both 13%), neutropenia and blurred vision (both 8%). Pharmacokinetics supported comparability of frozen-liquid and lyophilised presentations. Single-agent belamaf in a lyophilised presentation (intended for future use) showed a deep and durable clinical response and acceptable safety profile in patients with heavily pre-treated RRMM.

MM-219: Pivotal DREAMM-2 Study: Single-Agent Belantamab Mafodotin (Belamaf; GSK2857916) in Patients with Relapsed/Refractory Multiple Myeloma (RRMM) Refractory to Proteasome Inhibitors and Immunomodulatory Agents, and Refractory and/or Intolerant to Anti-CD38 Monoclonal Antibodies (mAbs), Including Subgroups with Renal Impairment (RI) and High-Risk (HR) Cytogenetics

Context: Belamaf showed deep and durable single-agent activity in the pivotal DREAMM-2 study primary analysis ( NCT03525678 ) (1–7) in a patient population that historically has a poor prognosis (overall survival [OS] 6–9 months). Objective: To present longer-term efficacy/safety outcomes (13-month follow-up) with single-agent belamaf in DREAMM-2 in the overall patient population and patients with HR cytogenetics and RI, subgroups with poor outcomes. Methods: DREAMM-2 is an ongoing study of belamaf 2.5 mg/kg (n=97) or 3.4 mg/kg (n=99). Primary outcome: overall response rate (ORR; ≥partial response). In post-hoc analyses, HR-cytogenetics included t(4;14), t(14;16), 17p13del, or 1q21 + . RI was based on eGFR (mild: ≥60– Results: Overall population ORRs in the 2.5 mg/kg and 3.4 mg/kg groups were 32% (97.5% CI: 21.7–43.6) and 35% (97.5% CI: 24.8–47.0); 19% and 23% of patients (58% and 66% of responders) achieved very good partial response or better. Median duration of response was 11.0 (95% CI: 4.2–not reached [NR]) and 6.2 months (95% CI: 4.8–NR). Median progression-free survival was 2.8 (95% CI: 1.6–3.6) and 3.9 months (95% CI: 2.0–5.8); median estimated OS was 13.7 (95% CI: 9.9–NR) and 13.8 months (95% CI: 10.0–NR). Most common Grade ≥3 adverse events (AEs) were keratopathy (microcyst-like epithelial changes [MECs] observed on eye examination; 2.5 mg/kg: 46%; 3.4 mg/kg: 42%), thrombocytopenia (2.5 mg/kg: 22%; 3.4 mg/kg: 32%), and anemia (2.5 mg/kg: 21%; 3.4 mg/kg: 27%). AE-related permanent discontinuation occurred in 9% and 12%; discontinuation due to MECs was rare (2.5 mg/kg: 1%; 3.4 mg/kg: 3%). HR cytogenetics and RI subgroup analyses will be presented at the conference. Conclusions: Deep and durable responses to single-agent belamaf were sustained and no new safety signals identified with longer follow-up in this heavily pretreated RRMM population. Funding: GSK (205678). Drug linker technology licensed from Seattle Genetics; mAb produced using POTELLIGENT Technology licensed from BioWa.

901P Matching-adjusted indirect comparisons (MAIC) of safety between single-agent belantamab mafodotin versus selinexor plus dexamethasone in relapsed/refractory multiple myeloma (RRMM)

901P Matching-adjusted indirect comparisons (MAIC) of safety between single-agent belantamab mafodotin versus selinexor plus dexamethasone in relapsed/refractory multiple myeloma (RRMM)

DREAMM-1 Patient perspectives from the first-in-human study of single-agent belantamab mafodotin for relapsed and refractory multiple myeloma (RRMM).

e20531 Background: Patient-reported outcomes in RRMM remain poor, particularly for those refractory to immunomodulatory agents, proteasome inhibitors, and anti-CD38 antibodies, and there is an increased risk of cumulative toxicities in these patients. Single-agent belantamab mafodotin (GSK2857916), a first-in-class, B-cell maturation antigen–binding immunoconjugate, has demonstrated deep and durable responses with a manageable safety profile in heavily pretreated patients with RRMM (DREAMM-1, NCT02064387). Here, we present patient-reported clinical benefit/tolerability of belantamab mafodotin evaluated by trial-embedded end-of-treatment (EOT) and follow-up interviews. Methods: DREAMM-1 study design and results have been reported ( Blood Cancer J 2019). Patients in the Part 2 expansion phase were administered single-agent belantamab mafodotin 3.4 mg/kg IV once every 3 weeks for 16 cycles and invited to participate in interviews at EOT and 6-month follow-up. Patients discussed symptoms, treatment-related adverse events (AEs), treatment burden, and overall treatment satisfaction, rated 0–10 (0 = not severe to 10 = most severe/0 = not at all satisfied to 10 = extremely satisfied). Results: A total of 17/35 patients (9 female [53%]) were interviewed; 4/17 patients completed both interviews. Most patients (94%; 16/17) achieved a partial response or better. At EOT, patients reported an improvement from the worst point in symptoms of bone pain (mean change in score from 6.4 to 4.0) and fatigue (8.0 to 5.5). The most commonly reported treatment-related AE was blurred vision (76%; 13/17). Among those reporting this AE, 62% (8/13) reported resolution or steady improvement in vision after EOT; with a reduction in severity rating from 7.3 at worst to 5.3 at EOT for this event. Most patients (93%; 13/14) never considered stopping treatment owing to AEs, including ocular events. Overall treatment satisfaction was high (mean score 7.9; median 9.0). Conclusions: Despite small sample sizes, trial-embedded interviews provide valuable insight into patient experience with belantamab mafodotin. Patients treated with single-agent belantamab mafodotin reported high treatment satisfaction and improvements in symptoms. Visual symptoms were frequent but manageable, and improved or resolved after treatment. Funding: GlaxoSmithKline (117159). Drug linker technology licensed from Seattle Genetics; monoclonal antibody produced using POTELLIGENT Technology licensed from BioWa. Clinical trial information: NCT02064387.

DREAMM-2: Single-agent belantamab mafodotin (GSK2857916) in patients with relapsed/refractory multiple myeloma (RRMM) and high-risk (HR) cytogenetics.

8541 Background: Patients with RRMM and HR cytogenetics have a poor prognosis and need effective therapies. In DREAMM-2 (NCT03525678), single-agent belantamab mafodotin (an immunoconjugate targeting B-cell maturation antigen) demonstrated clinically meaningful activity and a manageable safety profile in patients with heavily pretreated RRMM ( Lancet Oncol.2020). We present outcomes in patients with HR-cytogenetics (9-month follow-up). Methods: Patients with RRMM received single-agent belantamab mafodotin (2.5 or 3.4 mg/kg). For this post hoc analysis, HR-cytogenetics included t(4;14), t(14;16), 17p13del, or 1q21+ (tested locally). Results: The median number of cycles was 3 (2.5: range: 1–15) and 4 (3.4: range: 1–14). Overall response rate (ORR; ≥partial response [PR] per independent review committee) was 27% in the 2.5 mg/kg group (22% with ≥very good partial response [VGPR]) and 40% in the 3.4 mg/kg group (27% with ≥VGPR). The median duration of response (DoR) was not reached in the 2.5 mg/kg group and was 6.2 months in the 3.4 mg/kg group. The most common adverse events ( &gt; 30% in either group) were consistent with the overall population ( Lancet Oncol.2020): keratopathy (2.5: 59%;3.4: 79%), thrombocytopenia (2.5: 44%; 3.4: 65%), nausea (2.5: 27%; 3.4: 33%), anemia (2.5: 24%; 3.4: 42%), and blurred vision (2.5: 20%; 3.4: 42%). Conclusions: Patients with HR-cytogenetics maintain deep and durable clinical responses with single-agent belantamab mafodotin, comparable to that reported in the overall population. The safety profile remained consistent with previous reports. Funding: GlaxoSmithKline (205678). Drug linker technology licensed from Seattle Genetics; monoclonal antibody produced using POTELLIGENT Technology licensed from BioWa. Clinical trial information: NCT03525678 . [Table: see text]

Pivotal DREAMM-2 study: Single-agent belantamab mafodotin (GSK2857916) in patients with relapsed/refractory multiple myeloma (RRMM) refractory to proteasome inhibitors (PIs), immunomodulatory agents, and refractory and/or intolerant to anti-CD38 monoclonal antibodies (mAbs).

8536 Background: Single-agent belantamab mafodotin (B-cell maturation antigen targeting immunoconjugate) showed clinically meaningful activity and manageable safety in patients with heavily pre-treated RRMM (DREAMM-2, NCT03525678, Lancet Oncol.2020). We report updated results (median follow-up 9 months). Methods: DREAMM-2 is an ongoing single-agent belantamab mafodotin (2.5 or 3.4 mg/kg) study in patients with RRMM after ≥3 prior therapy lines and refractory to an immunomodulatory agent, a PI, and refractory and/or intolerant to an anti-CD38 mAb. Primary endpoint: overall response rate (ORR; ≥partial response per independent review committee). Results: ORR was 31% in the 2.5 mg/kg (19% with ≥very good partial responses [VGPR]) and 35% (24% with ≥VGPR) in the 3.4 mg/kg groups (Table). Duration of response (DoR) was not reached (NR) in the 2.5 mg/kg and 6.2 months in the 3.4 mg/kg groups; 1-year overall survival (OS) estimate was 53%. Common Grade 3/4 AEs ( &gt; 10% in either group) were keratopathy (2.5: 29%; 3.5: 24%), thrombocytopenia (2.5: 21%; 3.4: 32%), anemia (2.5: 20%; 3.4: 27%), pneumonia (2.5: 6%; 3.4: 13%), and neutropenia (2.5: 11%; 3.4: 16%). AEs were managed with dose delays (2.5: 54%; 3.4: 62%) and reductions (2.5: 34%; 3.4: 43%); discontinuations due to AEs were uncommon (2.5: 9%; 3.4: 12%). Conclusions: Single-agent belantamab mafodotin was well-tolerated, and clinically meaningful responses were sustained despite dose modifications with longer follow-up. Funding: GlaxoSmithKline (205678). Drug linker technology licensed from Seattle Genetics; monoclonal antibody produced using POTELLIGENT Technology licensed from BioWa. Clinical trial information: NCT03525678 . [Table: see text]