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SAFETY AND EFFICACY OF BELANTAMAB MAFODOTIN IN COMBINATION WITH RD IN NEWLY DIAGNOSED, TRANSPLANT INELIGIBLE MULTIPLE MYELOMA PATIENTS: A PHASE 1/2 STUDY BY THE HELLENIC SOCIETY OF HEMATOLOGY
Author(s): ,
Evangelos Terpos
Affiliations:
Department of Clinical Therapeutics,National and Kapodistrian University of Athens, School of Medicine,Athens,Grèce;Department of Clinical Therapeutics,National and Kapodistrian University of Athens, School of Medicine,Athens,Griechenland;Department of Clinical Therapeutics,National and Kapodistrian University of Athens, School of Medicine,Athens,Grecia;Department of Clinical Therapeutics,National
,
Maria Gavriatopoulou
Affiliations:
Department of Clinical Therapeutics,National and Kapodistrian University of Athens, School of Medicine,Athens,Grèce;Department of Clinical Therapeutics,National and Kapodistrian University of Athens, School of Medicine,Athens,Griechenland;Department of Clinical Therapeutics,National and Kapodistrian University of Athens, School of Medicine,Athens,Grecia;Department of Clinical Therapeutics,National
,
Ioannis Ntanasis-Stathopoulos
Affiliations:
Department of Clinical Therapeutics,National and Kapodistrian University of Athens, School of Medicine,Athens,Grèce;Department of Clinical Therapeutics,National and Kapodistrian University of Athens, School of Medicine,Athens,Griechenland;Department of Clinical Therapeutics,National and Kapodistrian University of Athens, School of Medicine,Athens,Grecia;Department of Clinical Therapeutics,National
,
Panagiotis Malandrakis
Affiliations:
Department of Clinical Therapeutics,National and Kapodistrian University of Athens, School of Medicine,Athens,Grèce;Department of Clinical Therapeutics,National and Kapodistrian University of Athens, School of Medicine,Athens,Griechenland;Department of Clinical Therapeutics,National and Kapodistrian University of Athens, School of Medicine,Athens,Grecia;Department of Clinical Therapeutics,National
,
Despina Fotiou
Affiliations:
Department of Clinical Therapeutics,National and Kapodistrian University of Athens, School of Medicine,Athens,Grèce;Department of Clinical Therapeutics,National and Kapodistrian University of Athens, School of Medicine,Athens,Griechenland;Department of Clinical Therapeutics,National and Kapodistrian University of Athens, School of Medicine,Athens,Grecia;Department of Clinical Therapeutics,National
,
Nikolaos Kanellias
Affiliations:
Department of Clinical Therapeutics,National and Kapodistrian University of Athens, School of Medicine,Athens,Grèce;Department of Clinical Therapeutics,National and Kapodistrian University of Athens, School of Medicine,Athens,Griechenland;Department of Clinical Therapeutics,National and Kapodistrian University of Athens, School of Medicine,Athens,Grecia;Department of Clinical Therapeutics,National
,
Stavros Gkolfinopoulos
Affiliations:
Health Data Specialists,Dublin,Irlande;Health Data Specialists,Dublin,Irland;Health Data Specialists,Dublin,Irlanda;Health Data Specialists,Dublin,Ireland;Health Data Specialists,Dublin,Irlanda;Health Data Specialists,Dublin,Ierland;Health Data Specialists,Dublin,Irlanda;Health Data Specialists,Dublin,Ирландия;Health Data Specialists,Dublin,Irland
,
Kyriaki Manousou
Affiliations:
Health Data Specialists,Dublin,Irlande;Health Data Specialists,Dublin,Irland;Health Data Specialists,Dublin,Irlanda;Health Data Specialists,Dublin,Ireland;Health Data Specialists,Dublin,Irlanda;Health Data Specialists,Dublin,Ierland;Health Data Specialists,Dublin,Irlanda;Health Data Specialists,Dublin,Ирландия;Health Data Specialists,Dublin,Irland
,
Efstathios Kastritis
Affiliations:
Department of Clinical Therapeutics,National and Kapodistrian University of Athens, School of Medicine,Athens,Grèce;Department of Clinical Therapeutics,National and Kapodistrian University of Athens, School of Medicine,Athens,Griechenland;Department of Clinical Therapeutics,National and Kapodistrian University of Athens, School of Medicine,Athens,Grecia;Department of Clinical Therapeutics,National
Meletios-Athanasios Dimopoulos
Affiliations:
Department of Clinical Therapeutics,National and Kapodistrian University of Athens, School of Medicine,Athens,Grèce;Department of Clinical Therapeutics,National and Kapodistrian University of Athens, School of Medicine,Athens,Griechenland;Department of Clinical Therapeutics,National and Kapodistrian University of Athens, School of Medicine,Athens,Grecia;Department of Clinical Therapeutics,National
(Abstract release date: 05/12/22) EHA Library. Terpos E. 06/10/22; 357042; S178
Prof. Evangelos Terpos
Prof. Evangelos Terpos
Contributions
Abstract
Presentation during EHA2022: All Oral presentations will be presented between Friday, June 10 and Sunday, June 12 and will be accessible for on-demand viewing from Monday, June 20 until Monday, August 15, 2022 on the Congress platform.

Abstract: S178

Type: Oral Presentation

Session title: Newly diagnosed multiple myeloma

Background
Belantamab mafodotin (belamaf), a multi-modal antibody-drug conjugate targeting BCMA, has shown efficacy and tolerability in pretreated patients (pts) with relapsed/refractory multiple myeloma. In pts refractory to immunomodulatory drugs, proteasome inhibitors, and antiCD38, belamaf plus pomalidomide and dexamethasone induced a very good partial response (VGPR) or better of 69.2% and a median progression-free survival of 16.2 months (Trudel S, ASH 2021). Preclinical evidence suggests that belamaf plus lenalidomide enhances antimyeloma activity, with no overlapping toxicities.

Aims

To evaluate the safety and efficacy of belamaf plus lenalidomide and dexamethasone (Rd) in transplant-ineligible (TI) pts with newly diagnosed multiple myeloma (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 Eastern Cooperative Oncology Group status 0–2 and adequate organ function. Part 1 (dose selection) evaluates the safety/tolerability of 3 belamaf doses (2.5, 1.9, and 1.4 mg/kg on Day 1 of every other 28-day cycle) plus Rd (each dose regimen administered to a cohort of 6 pts) over ≥4 weeks of follow up; subsequently, an additional 6 pts are enrolled in each dose cohort to establish the recommended phase 2 dose (RP2D). Part 2 (dose expansion) evaluates the safety and clinical activity of belamaf RP2D plus Rd in 30 additional pts. This descriptive analysis presents the safety data for all Part 1 pts and the efficacy data for all Part 1 pts with ≥2 post-baseline efficacy assessments by the cut-off date (14/01/2022).

Results

Of 36 pts included, 35 (97.2%) continued study treatment by the cut-off date, and 1 (2.8%) had died due to a belamaf unrelated adverse event (AE). The pt median age was 72.5 years (range 64.0–86.0). Of pts with available data (30 [83.3%]), pts at revised International Staging System stages I, II, and III were 6 [20.0%], 21 [70.0%], and 3 [10.0%], respectively, and 3 (10.0%) had high-risk cytogenetics (i.e., del17p13, t(4;14), t[14;16]). Median duration of therapy was 4.2 months (range 0.5–11.9) and median number of cycles reached was 5.0 (range 1.0–11.0). Twenty-two (61.1%) pts experienced at least one grade (Gr) 3–4 AE. One (2.8%) pt experienced a Gr 5 AE (pneumonia), unrelated to belamaf. Most common (≥ 10.0% of pts) Gr 3–4 AE were fatigue (13 [36.1%] pts), visual acuity reduced (6 [16.7%] pts), and rash (5 [13.9%] pts). Gr 3–4 thrombocytopenias and infections were not reported, as were any Gr infusion-related reactions (Table). Pts with Gr 1–2 ocular symptoms, visual acuity reduced, and keratopathy, were 27 (75.0%), 21 (58.3%), and 18 (50.0%), respectively. Pts with Gr 3–4 ocular symptoms, visual acuity reduced, and keratopathy were 0 (0.0%), 5 (13.9%) and 0 (0.0%), respectively. Of all pts, 28 (77.8%) were evaluable for efficacy (Table). At a median follow up of 4.2 months (range 0.5–11.9), the overall response rate was 96.4% (27/28 pts; complete response [CR]: 14.3% [4/28 pts]; VGPR: 35.7% [10/28 pts]; partial response [PR]: 46.4% [13/28 pts]); no disease progression was reported. Of pts achieving VGPR, 6/10 (60.0%) had negative status serum/urine immunofixation electrophoresis. Median time to PR or better was 1.0 months (range 0.9–2.0).

Conclusion
In pts with TI NDMM, belamaf every 2 months plus Rd showed an improved safety profile, especially at lower doses. Rapid and deep hematological responses were recorded.

Keyword(s): Clinical trial, Multiple myeloma

Presentation during EHA2022: All Oral presentations will be presented between Friday, June 10 and Sunday, June 12 and will be accessible for on-demand viewing from Monday, June 20 until Monday, August 15, 2022 on the Congress platform.

Abstract: S178

Type: Oral Presentation

Session title: Newly diagnosed multiple myeloma

Background
Belantamab mafodotin (belamaf), a multi-modal antibody-drug conjugate targeting BCMA, has shown efficacy and tolerability in pretreated patients (pts) with relapsed/refractory multiple myeloma. In pts refractory to immunomodulatory drugs, proteasome inhibitors, and antiCD38, belamaf plus pomalidomide and dexamethasone induced a very good partial response (VGPR) or better of 69.2% and a median progression-free survival of 16.2 months (Trudel S, ASH 2021). Preclinical evidence suggests that belamaf plus lenalidomide enhances antimyeloma activity, with no overlapping toxicities.

Aims

To evaluate the safety and efficacy of belamaf plus lenalidomide and dexamethasone (Rd) in transplant-ineligible (TI) pts with newly diagnosed multiple myeloma (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 Eastern Cooperative Oncology Group status 0–2 and adequate organ function. Part 1 (dose selection) evaluates the safety/tolerability of 3 belamaf doses (2.5, 1.9, and 1.4 mg/kg on Day 1 of every other 28-day cycle) plus Rd (each dose regimen administered to a cohort of 6 pts) over ≥4 weeks of follow up; subsequently, an additional 6 pts are enrolled in each dose cohort to establish the recommended phase 2 dose (RP2D). Part 2 (dose expansion) evaluates the safety and clinical activity of belamaf RP2D plus Rd in 30 additional pts. This descriptive analysis presents the safety data for all Part 1 pts and the efficacy data for all Part 1 pts with ≥2 post-baseline efficacy assessments by the cut-off date (14/01/2022).

Results

Of 36 pts included, 35 (97.2%) continued study treatment by the cut-off date, and 1 (2.8%) had died due to a belamaf unrelated adverse event (AE). The pt median age was 72.5 years (range 64.0–86.0). Of pts with available data (30 [83.3%]), pts at revised International Staging System stages I, II, and III were 6 [20.0%], 21 [70.0%], and 3 [10.0%], respectively, and 3 (10.0%) had high-risk cytogenetics (i.e., del17p13, t(4;14), t[14;16]). Median duration of therapy was 4.2 months (range 0.5–11.9) and median number of cycles reached was 5.0 (range 1.0–11.0). Twenty-two (61.1%) pts experienced at least one grade (Gr) 3–4 AE. One (2.8%) pt experienced a Gr 5 AE (pneumonia), unrelated to belamaf. Most common (≥ 10.0% of pts) Gr 3–4 AE were fatigue (13 [36.1%] pts), visual acuity reduced (6 [16.7%] pts), and rash (5 [13.9%] pts). Gr 3–4 thrombocytopenias and infections were not reported, as were any Gr infusion-related reactions (Table). Pts with Gr 1–2 ocular symptoms, visual acuity reduced, and keratopathy, were 27 (75.0%), 21 (58.3%), and 18 (50.0%), respectively. Pts with Gr 3–4 ocular symptoms, visual acuity reduced, and keratopathy were 0 (0.0%), 5 (13.9%) and 0 (0.0%), respectively. Of all pts, 28 (77.8%) were evaluable for efficacy (Table). At a median follow up of 4.2 months (range 0.5–11.9), the overall response rate was 96.4% (27/28 pts; complete response [CR]: 14.3% [4/28 pts]; VGPR: 35.7% [10/28 pts]; partial response [PR]: 46.4% [13/28 pts]); no disease progression was reported. Of pts achieving VGPR, 6/10 (60.0%) had negative status serum/urine immunofixation electrophoresis. Median time to PR or better was 1.0 months (range 0.9–2.0).

Conclusion
In pts with TI NDMM, belamaf every 2 months plus Rd showed an improved safety profile, especially at lower doses. Rapid and deep hematological responses were recorded.

Keyword(s): Clinical trial, Multiple myeloma

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