Program: Oral and Poster Abstracts
Session: 653. Myeloma: Therapy, excluding Transplantation: Immunotherapy in Myeloma and Amyloid
Methods: Forty patients will be recruited in this trial. Patients aged ≥18 years with evaluable AL amyloidosis, who have received ≥1 prior therapy and are not in very good partial response (VGPR) or better with a measurable plasma cell dyscrasia with dFLC > 50 mg/L (difference between involved and uninvolved free light chain levels), with at least one major vital organ involvement, with ECOG performance status 0,1 or 2, no chronic atrial fibrillation, a supine blood pressure > 100 mmHg and NT-proBNP < 8500 ng/L are eligible. They receive DARA intravenously in a standard schedule and dose: 16 mg/kg weekly during the first two 28-day cycles and every other week during cycles 3 through 6 for a total of six 28-day cycles. Hematologic responses are measured after 1 injection of DARA and at each cycle. The objectives are to assess hematologic responses, organ responses and safety.
Results: At data cut-off (July 31, 2017), 30 of the 40 planned patients have been enrolled in 9 French centers. The median age is 69 years (range, 45-81), and median number of prior therapies is 2.5 (range, 1-5): 13 patients (43%) have received Melphalan and Dexamethasone, 28 patients (93%) bortezomib, and 14 patients (46%) lenalidomide. The median time from diagnosis to enrollment is 23 months (range, 3.5-116). The median number of organ system involvement is 2 (range, 1-5), 8 patients (27%) have >2 organ system involvement, 18 patients (60%) have cardiac and 16 patients (53%) renal involvement, 14 patients (47%) have cardiac biomarker stage II and 4 patients (13%) stage III disease. There was one on-study death due to cardiac progression. Four patients have discontinued study treatment before 6 cycles due to disease progression (n=2), death (n=1) or lung cancer (n=1). Nine patients have received 6 cycles and 17 patients are on therapy. Six patients (20 %) experienced at least one grade ≥3 AE (any cause) and only one was considered as drug related (lymphopenia). The most common drug-related AEs were infusion reaction in 10 patients (33%), all grade I or II. Hematologic complete response (CR) was observed in 4 of 24 evaluable (completing at least 1 cycle) patients (17%), VGPR in 7 patients (29%) and partial response in 4 patients (17%). The overall response rate is 63%. The responses were usually very rapid (Figure 1). After a single DARA injection all 15 responding patients had a decrease in dFLC of more than 30 % with a median dFLC decrease after 1 injection in these 15 responding patients of 57% (range 31-96).
Conclusion: Daratumumab demonstrates encouraging efficacy in previously-treated patients with AL amyloidosis with deep and rapid responses. The administration of DARA in these patients is associated with a good safety profile and non-severe adverse events mostly after the first infusion. Further studies on DARA-based associations in AL amyloidosis patients are warranted. The data will be updated at the meeting.
Disclosures: Roussel: JANSSEN: Honoraria, Research Funding. Perrot: Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Honoraria; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria; Sanofi: Honoraria; Amgen: Honoraria. Macro: JANSSEN: Honoraria. Frenzel: Shire: Research Funding. Palladini: Jannsen-Cilag: Membership on an entity's Board of Directors or advisory committees; Celgene: Other: Travel grants; Prothena: Honoraria, Other: Travel grant. Jaccard: Celgene: Honoraria, Other: Travel expenses, Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel expenses, Research Funding; Amgen: Honoraria.
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