Session: 652. Multiple Myeloma and Plasma Cell Dyscrasias: Clinical and Epidemiological: Poster I
Hematology Disease Topics & Pathways:
The analysis included consecutive pts with AL amyloidosis treated in the Department of Clinical Therapeutics, Athens Greece, who received DARA-based therapy, at any time during the course of their disease. Overall, 116 pts with AL amyloidosis received therapy with DARA and the analysis focused on 31 (26.7%) that either relapsed after DARA discontinuation or were refractory to DARA or had non-satisfactory response requiring further therapy.
The characteristic of these 31 pts at the time of initial diagnosis, included cardiac involvement in 27 (87%), renal in 15 (48%), liver in 4 (13%), PNS in 5 (16%) and 9 (29%) had soft tissue involvement. Baseline Mayo stage was 3% / 45% / 48% for stages 1 / 2 / 3 [6 (19%) were Mayo 3b] and renal stage distribution was 55% / 32% / 10% for stages 1 / 2 / 3. Translocation (11;14) (in 29%), and +1q21 (in 26%) of pts were the most common cytogenetic abnormalities.
At DARA index therapy, 23 (74.2%) pts had received DARA monotherapy and 8 (25.8%) in combinations (mainly with bortezomib); in 13 (42%) pts as first line and in 18 (58%) as salvage therapy; the median number of treatments prior to DARA index therapy was 1 (range 0-4). DARA was given as salvage therapy in 11 (61.1%) pts due to inadequate hematologic response to prior therapy, in 6 (33.3%) due to hematologic relapse or progression and in 1 (5.6%) due to organ progression. Median duration of DARA therapy was 2.8 months (range 0.5-31.7 months) and on ITT the hematologic response rate at index DARA therapy was 61.3% [CR/VGPR: 10 (32.3%), PR: 9 (29%)].
DARA failure was due to hematologic relapse in 18 (58%) pts, inadequate hematologic response in 11 (32%) and in 2 (6.5%) due to organ progression; the median time to “failure” during or after therapy with DARA was 13.6 months (0.5-43.6); at the time of DARA failure, 8 (26%) pts had had an organ response and 5 (16%) organ progression. At the time of DARA failure, 26 pts (84%) were exposed to bortezomib, 15 (48%) to lenalidomide and 3 (10%) to melphalan. Treatments post DARA failure included re-treatment with DARA combinations (with bortezomib or IMiDs) in 9 (29%) pts, venetoclax in 3 (9.7%) pts, belantamab mafodotin in 4 (12.9%) pts, bortezomib-based regimens in 6 (19.4%) pts, lenalidomide-based in 3 (9.7%) pts, pomalidomide in 3 (9.7%) pts, ixazomib in 2 patient (6.4%) and alkylating agent in 1 patient (3.2%). Median NTproBNP at start of post DARA therapy was 3936 ng/L and median dFLC was 123 mg/L. Hematologic response rate was 55% [VGPR/CR: 14 pts (45%), PR: 3 pts (10%)]; organ responses were observed in 9 pts (29%) and organ progression in 16 pts (51.6%). Among the 9 pts retreated with DARA-based regimens, 2 (22.2%) achieved VGPR and for non-DARA regimens hematologic response rate was 68.1% [CR/VGPR: 12 (54.5%), PR: 3 (13.6%)]. Ten pts (32.3%) have died; 1- and 2-year survival rate from the start of post DARA therapy was 64% and 55%. In univariate analysis, factors that were associated with inferior survival post DARA were NTproBNP (p=0.002), ALP (p<0.001) and dFLC (p=0.025) levels. Pts that failed DARA due to inadequate hematologic response had inferior survival than those that started therapy due to hematologic relapse, but the difference was not statistically significant (p=0.279) (Fig 1).
In conclusion, treatment of pts with AL amyloidosis who have failed DARA therapy is feasible, based on the use of non-cross resistant drugs or other targeted therapies. Hematologic responses in 55% and a 2-year survival of 55% in this difficult to treat population are respectful and set the benchmark for the evaluation of new therapies in this setting. Re-treatment with DARA may not be the best option, but more data are needed.
Disclosures: Gavriatopoulou: Genesis Pharma: Honoraria; GSK: Consultancy, Honoraria; Janssen Cilag: Honoraria; Sanofi: Honoraria; Karyopharm: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Amgen: Consultancy, Honoraria. Terpos: EUSA Pharma: Honoraria, Other: Travel expenses; Amgen: Honoraria, Other: Travel expenses, Research Funding; BMS: Honoraria; Sanofi: Honoraria, Research Funding; Takeda: Honoraria, Other: Travel expenses, Research Funding; Novartis: Honoraria; Janssen: Honoraria, Research Funding; GSK: Honoraria, Research Funding; Genesis: Honoraria, Research Funding. Dimopoulos: BeiGene: Honoraria; Amgen: Honoraria; BMS: Honoraria; Jannsen: Honoraria; TAKEDA: Honoraria. Kastritis: Pfizer: Honoraria, Research Funding; GSK: Honoraria; Genesis Pharma: Honoraria; Janssen: Honoraria, Research Funding; Amgen: Honoraria, Research Funding; Takeda: Honoraria.
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