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EFFICACY AND SAFETY OF BELANTAMAB MAFODOTIN MONOTHERAPY IN PATIENTS WITH RELAPSED OR REFRACTORY LIGHT CHAIN AMYLOIDOSIS: A PHASE 2 STUDY BY THE EUROPEAN MYELOMA NETWORK
Author(s): ,
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
,
Giovanni Palladini
Affiliations:
Amyloidosis Research and Treatment Center,University of Pavia,Pavia,Italie;Amyloidosis Research and Treatment Center,University of Pavia,Pavia,Italien;Amyloidosis Research and Treatment Center,University of Pavia,Pavia,Italia;Amyloidosis Research and Treatment Center,University of Pavia,Pavia,Italy;Amyloidosis Research and Treatment Center,University of Pavia,Pavia,Italia;Amyloidosis Research and
,
Meletios A. 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
,
Arnaud Jaccard
Affiliations:
Referral Center for AL amyloidosis,Limoges,France;Referral Center for AL amyloidosis,Limoges,Frankreich;Referral Center for AL amyloidosis,Limoges,Francia;Referral Center for AL amyloidosis,Limoges,France;Referral Center for AL amyloidosis,Limoges,Francia;Referral Center for AL amyloidosis,Limoges,Frankrijk;Referral Center for AL amyloidosis,Limoges,França;Referral Center for AL amyloidosis,Limoge
,
Giampaolo Merlini
Affiliations:
Amyloidosis Research and Treatment Center,University of Pavia,Pavia,Italie;Amyloidosis Research and Treatment Center,University of Pavia,Pavia,Italien;Amyloidosis Research and Treatment Center,University of Pavia,Pavia,Italia;Amyloidosis Research and Treatment Center,University of Pavia,Pavia,Italy;Amyloidosis Research and Treatment Center,University of Pavia,Pavia,Italia;Amyloidosis Research and
,
Foteini Theodorakakou
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
,
Despoina 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
,
Monique C. Minnema
Affiliations:
Department of Hematology,University Medical Center Utrecht,Utrecht,Pays-bas;Department of Hematology,University Medical Center Utrecht,Utrecht,Niederlande;Department of Hematology,University Medical Center Utrecht,Utrecht,Paesi Bassi;Department of Hematology,University Medical Center Utrecht,Utrecht,Netherland;Department of Hematology,University Medical Center Utrecht,Utrecht,Países Bajos;Departme
,
Ashutosh Wechalekar
Affiliations:
Clinical Haematology, Cancer Division,University College London Hospital,London,Royaume-uni;Clinical Haematology, Cancer Division,University College London Hospital,London,Vereinigtes Königreich;Clinical Haematology, Cancer Division,University College London Hospital,London,Regno Unito;Clinical Haematology, Cancer Division,University College London Hospital,London,United Kingdom;Clinical Haematolo
,
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
,
Pieter Sonneveld
Affiliations:
Erasmus MC Cancer Institute,Rotterdam,Pays-bas;Erasmus MC Cancer Institute,Rotterdam,Niederlande;Erasmus MC Cancer Institute,Rotterdam,Paesi Bassi;Erasmus MC Cancer Institute,Rotterdam,Netherland;Erasmus MC Cancer Institute,Rotterdam,Países Bajos;Erasmus MC Cancer Institute,Rotterdam,Nederland;Erasmus MC Cancer Institute,Rotterdam,Holanda;Erasmus MC Cancer Institute,Rotterdam,Нидерланды;Erasmus MC
Stefan Schönland
Affiliations:
University of Heidelberg,Heidelberg,Allemagne;University of Heidelberg,Heidelberg,Deutschland;University of Heidelberg,Heidelberg,Germania;University of Heidelberg,Heidelberg,Germany;University of Heidelberg,Heidelberg,Alemania;University of Heidelberg,Heidelberg,Duitsland;University of Heidelberg,Heidelberg,Alemanha;University of Heidelberg,Heidelberg,Германия;University of Heidelberg,Heidelberg,
(Abstract release date: 05/12/22) EHA Library. Kastritis E. 06/10/22; 357774; P914
Dr. Efstathios Kastritis
Dr. Efstathios Kastritis
Contributions
Abstract
Presentation during EHA2022: All (e)Poster presentations will be made available as of Friday, June 10, 2022 (09:00 CEST) and will be accessible for on-demand viewing until Monday, August 15, 2022 on the Congress platform.

Abstract: P914

Type: Poster presentation

Session title: Myeloma and other monoclonal gammopathies - Clinical

Background
Managing patients (pts) with relapsed/refractory (RR) light chain (AL) amyloidosis is challenging, as there is no current standard treatment, many available options are associated with low efficacy and toxicity, and options for daratumumab (DARA)- and bortezomib-exposed patients are limited. Belantamab mafodotin (belamaf), a multi-modal antibody-drug conjugate targeting BCMA, has shown efficacy and tolerability in heavily pretreated pts with RR multiple myeloma, including those refractory to DARA. Since clonal plasma cells in AL amyloidosis and MM are phenotypically similar, belamaf could be a novel treatment option in AL amyloidosis.

Aims
To evaluate the efficacy and safety of belamaf monotherapy off-label in pts with RR AL amyloidosis.

Methods
The ongoing prospective, open-label, multinational, phase 2, EMN27 study (NCT04617925) aims to enroll 36 adult pretreated pts with AL amyloidosis who require therapy. Pts at Mayo cardiac stage 3b are excluded. Belamaf monotherapy at 2.5mg/kg is administered by intravenous infusion every 6 weeks for a maximum of 8 cycles; dosing can be reduced to 1.92mg/kg for toxicity. Per study design, a safety analysis (after 6 pts received ≥1 treatment cycle) and an efficacy analysis (after 13 pts are enrolled) were planned. The safety analysis revealed no new safety signals, and pt accrual continued to 13 pts. The efficacy analysis is currently conducted; however, already 3 pts achieved complete response, or very good partial response (VGPR), or low difference of involved to uninvolved serum free light chains (dFLC) response and enrollment is continuing to include all planned pts. This descriptive analysis included pts initiating study treatment ≥3 months before the cut-off date (15/01/2022).

Results
Of 11 pts included in the analysis, 4 (36.4%) continued treatment by the cut-off date, and 7 (63.6%) discontinued (disease progression: 5 [45.5%], death: 2 [18.2%]). The pts median age was 69.0 years (range 46.0–80.0), and most were males (7, 63.6%). At baseline, 3 (27.3%) and 8 (72.7%) pts had New York Heart Association class I and II symptoms, respectively; the median N-terminal pro-brain natriuretic peptide, high-sensitivity troponin T, and dFLC were 1,979 pg/mL (range 190.0–4,135.0), 41.6 pg/mL (range 11.0–80.8), and 34.2mg/dl (range 4.4–279.1), respectively. Except for the heart, commonly involved organs were the nervous system (4 pts, 36.4%) and the soft tissue (2 pts, 18.2%). The median number of previous AL amyloidosis treatments was 3.0 (range 1.0–7.0), including DARA. The median duration of belamaf therapy was 3.1 months (range 1.4–5.7). At a median follow up of 9.4 months (range 3.1–10.0), the overall response rate was 72.7% (8 pts; VGPR: 27.3% [3 pts] and partial response: 45.5% [5 pts]). Median time to first hematological response was 8.5 days (range 1.0–28.0) and to VGPR or better 15.0 days (range 8.0–15.0). The 3-month organ (heart, kidney, or liver) response rate was 36.4% (4 pts). All pts had ≥1 non serious adverse event (SAE). Four (36.4%) pts had ≥1 SAE, including 2 (18.2%) pts with a belamaf-related grade 2 and 4 visual impairment (1 [9.1%] pt each). Eight (72.7%) pts had ≥1 adverse event of special interest. Two (18.2%) pts had a fatal SAE (pneumonia and intestinal perforation, 1 [9.1%] pt each), both unrelated to belamaf.

Conclusion
In this prospective study, belamaf monotherapy induced rapid, clinically meaningful responses with a manageable safety profile in heavily pretreated pts with RR AL amyloidosis. As the study progresses, additional data will be generated.

Keyword(s): AL amyloidosis, Safety

Presentation during EHA2022: All (e)Poster presentations will be made available as of Friday, June 10, 2022 (09:00 CEST) and will be accessible for on-demand viewing until Monday, August 15, 2022 on the Congress platform.

Abstract: P914

Type: Poster presentation

Session title: Myeloma and other monoclonal gammopathies - Clinical

Background
Managing patients (pts) with relapsed/refractory (RR) light chain (AL) amyloidosis is challenging, as there is no current standard treatment, many available options are associated with low efficacy and toxicity, and options for daratumumab (DARA)- and bortezomib-exposed patients are limited. Belantamab mafodotin (belamaf), a multi-modal antibody-drug conjugate targeting BCMA, has shown efficacy and tolerability in heavily pretreated pts with RR multiple myeloma, including those refractory to DARA. Since clonal plasma cells in AL amyloidosis and MM are phenotypically similar, belamaf could be a novel treatment option in AL amyloidosis.

Aims
To evaluate the efficacy and safety of belamaf monotherapy off-label in pts with RR AL amyloidosis.

Methods
The ongoing prospective, open-label, multinational, phase 2, EMN27 study (NCT04617925) aims to enroll 36 adult pretreated pts with AL amyloidosis who require therapy. Pts at Mayo cardiac stage 3b are excluded. Belamaf monotherapy at 2.5mg/kg is administered by intravenous infusion every 6 weeks for a maximum of 8 cycles; dosing can be reduced to 1.92mg/kg for toxicity. Per study design, a safety analysis (after 6 pts received ≥1 treatment cycle) and an efficacy analysis (after 13 pts are enrolled) were planned. The safety analysis revealed no new safety signals, and pt accrual continued to 13 pts. The efficacy analysis is currently conducted; however, already 3 pts achieved complete response, or very good partial response (VGPR), or low difference of involved to uninvolved serum free light chains (dFLC) response and enrollment is continuing to include all planned pts. This descriptive analysis included pts initiating study treatment ≥3 months before the cut-off date (15/01/2022).

Results
Of 11 pts included in the analysis, 4 (36.4%) continued treatment by the cut-off date, and 7 (63.6%) discontinued (disease progression: 5 [45.5%], death: 2 [18.2%]). The pts median age was 69.0 years (range 46.0–80.0), and most were males (7, 63.6%). At baseline, 3 (27.3%) and 8 (72.7%) pts had New York Heart Association class I and II symptoms, respectively; the median N-terminal pro-brain natriuretic peptide, high-sensitivity troponin T, and dFLC were 1,979 pg/mL (range 190.0–4,135.0), 41.6 pg/mL (range 11.0–80.8), and 34.2mg/dl (range 4.4–279.1), respectively. Except for the heart, commonly involved organs were the nervous system (4 pts, 36.4%) and the soft tissue (2 pts, 18.2%). The median number of previous AL amyloidosis treatments was 3.0 (range 1.0–7.0), including DARA. The median duration of belamaf therapy was 3.1 months (range 1.4–5.7). At a median follow up of 9.4 months (range 3.1–10.0), the overall response rate was 72.7% (8 pts; VGPR: 27.3% [3 pts] and partial response: 45.5% [5 pts]). Median time to first hematological response was 8.5 days (range 1.0–28.0) and to VGPR or better 15.0 days (range 8.0–15.0). The 3-month organ (heart, kidney, or liver) response rate was 36.4% (4 pts). All pts had ≥1 non serious adverse event (SAE). Four (36.4%) pts had ≥1 SAE, including 2 (18.2%) pts with a belamaf-related grade 2 and 4 visual impairment (1 [9.1%] pt each). Eight (72.7%) pts had ≥1 adverse event of special interest. Two (18.2%) pts had a fatal SAE (pneumonia and intestinal perforation, 1 [9.1%] pt each), both unrelated to belamaf.

Conclusion
In this prospective study, belamaf monotherapy induced rapid, clinically meaningful responses with a manageable safety profile in heavily pretreated pts with RR AL amyloidosis. As the study progresses, additional data will be generated.

Keyword(s): AL amyloidosis, Safety

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