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3408 High Responses Rates with Single Agent Belantamab Mafodotin in Relapsed Systemic AL AmyloidosisClinically Relevant Abstract

Program: Oral and Poster Abstracts
Session: 654. MGUS, Amyloidosis and Other Non-Myeloma Plasma Cell Dyscrasias: Clinical and Epidemiological: Poster II
Hematology Disease Topics & Pathways:
Research, Clinical Practice (Health Services and Quality), Clinical Research, real-world evidence
Sunday, December 10, 2023, 6:00 PM-8:00 PM

Jahanzaib Khwaja1, Joshua Bomsztyk2*, Ceri Bygrave, MD, FRCPath, MPhil3*, Adam Forbes4*, Senthilkumar Durairaj5*, Savio Fernandes6*, James Taylor7*, Pamela Paterson8*, Gillian Brearton9*, Charles Crawley, MD10*, Oonagh Sheehy11*, Rachel Brown12*, Richard Soutar, MD13*, Mamta Garg, MD, MBBS, FRCP, FRCPath14*, Andrzej Rydzewski15*, Krzysztof Jamroziak16*, Emma Dowling1*, Nuno Correia1*, Sarah Worthington1*, Shameem Mahmood1,2* and Ashutosh D. Wechalekar, MBBS, DM, FRCP, FRCPath1,2

1University College London Hospitals, London, United Kingdom
2Royal Free London Hospital, National Amyloid Centre, London, United Kingdom
3Haematology, University Hospital Wales, Cardiff, United Kingdom
4Royal Cornwall Hospital NHS Trust, Truro, United Kingdom
5Hull University Teaching Hospitals NHS Trust, Hull, United Kingdom
6The Dudley Group NHS Foundation Trust, Dudley, United Kingdom
7Rotherham NHS Foundation Trust, Rotherham, United Kingdom
8Monklands Hospital, Lanarkshire, United Kingdom
9Clatterbridge Cancer Centre, Liverpool, United Kingdom
10Addenbrookes Hospital, Cambridge, United Kingdom
11Belfast Health and Social Care Trust, Belfast, United Kingdom
12Manchester University NHS Foundation Trust, Manchester, United Kingdom
13Glasgow Royal Infirmary, Glasgow, United Kingdom
14University Hospitals of Leicester NHS Trust, Leicester, United Kingdom
15The National Institute of Medicine of the Ministry of Interior and Administration, Warsaw, Poland
16Institute of Hematology and Blood Transfusion, Warsaw, Poland


Systemic AL amyloidosis, a rare incurable plasma cell disorder, has no approved treatments at relapse. Belantamab mafodotin is an antibody-drug conjugate which targets BCMA antigen approved for relapsed refractory myeloma. We report our results using belantamab mafodotin monotherapy for the treatment of patients with relapsed refractory AL amyloidosis including those traditionally excluded from clinical trials (eGFR<30 ml/min/1.73m2 and cardiac Mayo stage IIIb disease).


All patients treated with belantamab mafodotin monotherapy at standard dose (2.5 mg/kg) or dose reduction between April 2021 - July 2023. Standardised assessments including measurement of cardiac biomarkers, clonal parameters and imaging were performed and disease assessment was reported as per International Society of Amyloidosis consensus criteria.


Twenty-seven patients were included. The median age at was 65 years (range 41-76) and eight (30%) patients were aged >70 years. Eighteen (67%) had λ AL-type and nine (33%) κ AL-type. A median of two organs were involved at baseline (range 1-4) with renal and cardiac involvement in 20 (74%) and 15 (56%) respectively (3 each for Mayo stage IIIa and stage IIIb).

The median time from AL amyloidosis diagnosis to first administration of belantamab mafodotin was 69 (range 5-174) months (~6 years) with a median of 3 prior lines of treatment (range 2-6). Prior drug class exposure included proteasome inhibitors (100%), immunomodulatory drugs (81%) and anti-CD38 antibody (81%) therapy. Ten patients (37%) had undergone prior melphalan-conditioned autologous stem cell transplantation.

At the time of first belantamab mafodotin dose, the median involved free light chain concentration was 118mg/l (range 31-1778), eGFR was 40 ml/min (range 7 – 120) and a third (9/27) with an eGFR <30 ml/min/1.73m2. NT-proBNP was 845 ng/l (range 99-70,000).

At data cut-off, a median of 5 (range 1-11) doses of belantamab mafodotin were delivered. Of those with evaluable disease, best haematological overall response rate (partial response or better) was 80% (20/25) at a median time to best haematological response of 2 months (95% CI 1-4, range 1-17). Complete response (CR) or very good partial response (VGPR) was achieved in 64% (16/25). Two patients have only had 1 cycle and too early to perform response assessment.

Reasons for treatment discontinuation (n=12) were: inadequate response/progression (n=7), keratopathy (n=1), grade 3 thrombocytopenia (n=1), physician choice (n=3: discontinued due to treatment for unrelated metastatic squamous cell carcinoma but remains in CR; facilitation of renal transplant; prior to BCMA-directed CAR-T in VGPR).

At a median follow-up of 13 months follow-up (95% CI 4-18, range 1-27) from belantamab mafodotin initiation, 15 patients (56%) remain on therapy. Two patients died (1 due to progressive disease, 1 unrelated) and seven patients progressed and had subsequent line of therapy at a median time of 6 months (95% CI 2-4) in those that had a next line of therapy. Median treatment-free survival or death was 27 months (10-NR), and 1-year treatment-free survival/death was 69% (95% CI 41-86). Median overall survival (OS) is not reached. 1-year OS is 88% (95% CI 59-97).

Bilateral microcystic corneal keratopathy, the most frequent adverse event, was seen in 19 (70%) patients (5%; 1/19 grade 4). Ocular adverse events improved in all patients after treatment delay. Only one patient required treatment cessation due to ocular toxicity (despite achieving PR after one dose). Thrombocytopenia was reported in 3 (11%) (grade 3: 1; grade 2: 1). Only two patients remained on the standard dose of 2.5mg/kg for >3 cycles. Nine patients had eGFR <30ml/min and 6/9 started at a dose of 1.25mg/kg with no unexpected side effects (1 patient had grade 3 keratopathy). One patient post-renal transplantation (on tacrolimus and mycophenolate) had no significant toxicity and achieved a CR after cycle 3. No treatment-related deaths, cardiac or renal toxicities observed in our cohort.


Belantamab mafadotin has high efficacy and good tolerability in multiply relapsed AL amyloidosis including efficacy in patients otherwise excluded from clinical trials. Treatment-emergent adverse events (especially keratopathy) do not preclude delivery of drug with appropriate dose reductions.

Disclosures: Garg: Stemline therapeutics Janssen: Other: Ad board; Celgene: Other: Ad board; Sanofi: Membership on an entity's Board of Directors or advisory committees; Alnylam: Honoraria; Janssen: Consultancy, Honoraria, Other: Ad board, research support, Speakers Bureau; Takeda: Consultancy, Honoraria, Other: Ad board, travel support; BMS: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Consultancy, Honoraria, Other: Ad board, travel support; GSK: Consultancy, Honoraria. Wechalekar: GSK: Honoraria; Takeda: Other: Travel support; Alexion: Honoraria; Janssen: Honoraria; Attralus: Honoraria; Alexion, Attralus, Janssen, Prothena.: Consultancy.

*signifies non-member of ASH