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4781 Outcomes of Second Line Therapy for Light Chain Amyloidosis after Initial Therapy with a Bortezomib Based RegimenClinically Relevant Abstract

Program: Oral and Poster Abstracts
Session: 654. MGUS, Amyloidosis and Other Non-Myeloma Plasma Cell Dyscrasias: Clinical and Epidemiological: Poster III
Hematology Disease Topics & Pathways:
Therapies, therapy sequence
Monday, December 11, 2023, 6:00 PM-8:00 PM

Lipi Chakravorty, MBBS1*, Anthea Gibbons, MBBS2*, Nirija Anderson3*, Fiona Kwok, FRACP, FRCPA, MBBS4*, Dariusz Korczyk, MBBS, FRACP5*, Emad Uddin Abro, MBBS, BSc, FRACP, FRCPA6*, Stephanie Lam, MB BS7*, Simon Gibbs, FRACP, FRCPA, MBBS8,9*, Peter Mollee, FRACP, MBBS, MSc, FRCPA10,11 and M Hasib Sidiqi, MBBS, FRACP, FRCPA12,13*

1Haematology Department, Fiona Stanley Hospital, Perth, Australia
2Haematology Department, Princess Alexandra Hospital, Brisbane, Australia
3Princess Alexandra Hospital, Brisbane, QLD, Australia
4Westmead Hospital, Sydney, AUS
5Cardiology Department, Princess Alexandra Hospital, Woolloongabba, Australia
6Haematology Department, Princess Alexandra Hospital, Woolloongabba, Australia
7Fiona Stanley Hospital, Perth, Australia
8University of Melbourne, Greater Melbourne Area, AUS
9Eastern Health, Box Hill, Australia
10Faculty of Medicine, University of Queensland, Brisbane, QLD, Australia
11Department of Haematology, Princess Alexandra Hospital, Brisbane, QLD, Australia
12Department of Haematology, Fiona Stanley Hospital, Perth, Western Australia, Australia, Murdoch, Western Australia, AUS
13Curtin Medical School, Curtin University, Western Australia, Bentley, Western Australia, Australia

Introduction: There are a lack of randomized trials to guide therapy for relapsed AL amyloidosis with treatment regimens generally extrapolated from experience in multiple myeloma.

Methods: We conducted a retrospective review of bortezomib exposed patients that received second line therapy for AL amyloidosis at three Amyloidosis centres in Australia (Brisbane, Perth and Sydney). Of 190 patients treated with bortezomib based therapy upfront, 98 (52%) had transitioned to second line therapy during the study period and comprised the study cohort.

Results: Baseline characteristics for the study cohort were typical for a cohort with AL amyloidosis. Median age was 66 years, with 38% of patients being male. Cardiac and renal involvement was present in 70% of patients respectively. Seven patients (7%) had frontline therapy that included daratumumab. Median duration of frontline therapy was 5 months (range 2-18 months) and median time from diagnosis to second line therapy was 9 months (range 2-65 months). We categorized treatment regimens according to commonly used combinations and drug classes to further analyse outcomes. Six categories of therapy regimens were identified; autologous stem cell transplant (ASCT) (n=17), thalidomide based (n=12), lenalidomide based (n=13), proteasome inhibitor (PI) based (n=9), Anti-CD38 monoclonal antibody (mAB) based (n=38) and melphalan based (n=4). Five patients were excluded from this analysis as they received an atypical therapy/regimen not commonly used for AL amyloidosis. Overall response rate (ORR) for the whole cohort was 84%. The ORR was lowest for thalidomide and melphalan based therapy (67% and 50% respectively) and highest for patients receiving an ASCT or anti-CD38 mAB therapy (94% and 92% respectively), Figure 1a. Median event free survival (EFS) for the cohort from second line therapy was 17 months. Median duration of follow up from second line therapy for the cohort was 26 months . Median EFS was shortest for patients treated with thalidomide and melphalan based regimens (6 and 12 months respectively) and longest for those who received an ASCT (28 months) or anti- CD38 mAB therapy (not reached), Figure 1b. When comparing immunomodulatory drugs lenalidomide treated patients had a longer EFS (median 6 months for thalidomide vs 16 months for lenalidomide, p=0.09). The median overall survival (OS) for the cohort was 81 months. OS was longest amongst patients receiving an ASCT or anti-CD38 mAB therapy (median of 91 months and not reached, respectively). Survival was similar amongst patients treated with a PI or Immunomodulatory drug (median 41 months for thalidomide, 44 months for lenalidomide and 36 months for PI based therapy).

Conclusion: In bortezomib exposed AL amyloidosis patients, second line therapy with anti CD38 mAB’s induced deep responses and prolonged survival. Amongst immunomodulatory agents, the second generation agents appear to be more effective. In our cohort the small group of patients receiving repeat therapy with a PI also appeared to respond to treatment. Although an intensive treatment with significant risks, our data show that in select individuals an ASCT can induce deep and long lasting remissions. Our data highlights the variability in second line therapies for AL amyloidosis given the paucity of evidence to guide treatment. The recent addition of daratumumab as a standard of care for upfront therapy further limits options in the relapsed setting and highlights the need for trials using next generation novel anti plasma cell agents in this patient population.

Disclosures: Kwok: Pfizer: Research Funding. Gibbs: BMS: Honoraria; Jansen: Honoraria, Membership on an entity's Board of Directors or advisory committees. Mollee: Janssen: Research Funding; Pfizer: Research Funding; Cilag: Research Funding. Sidiqi: BMS: Speakers Bureau; Gilead: Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Antengene: Speakers Bureau; Pfizer: Membership on an entity's Board of Directors or advisory committees.

*signifies non-member of ASH