Dara VCD: Outcomes of frontline therapy for light-chain amyloidosis.

Abstract

e19574 Background: Daratumumab, bortezomib, cyclophosphamide, and dexamethasone (Dara-VCD) is an FDA-approved frontline treatment for AL amyloidosis with the ANDROMEDA trial demonstrating significantly improved outcomes. However, long-term real world data and the impact of cytogenetics require further study. Methods: This study included 77 patients from two institutions with AL amyloidosis who had frontline therapy of Dara-VCD or Dara-VD. Hematologic and organ responses, relapse and progression were identified per ISA criteria. Time to next treatment (TTNT) and event free survival (EFS) were measured from the date of the start of first line treatment. EFS events were defined as the earliest occurrence of hematological or organ progression, initiation of next-line therapy or death. Results: Of the 77 patients, 47 (61%) were male, with a median age of 67 years. AL lambda-type was present in 57 (74%) patients. Sixty-eight (88%) had cardiac involvement, while 54 (72%) had renal involvement (Table 1). After frontline therapy, 71/76 (93%) had hematological responses, including 23 (30%) CR and 37 (49%) VGPR; 35/53 (66%) had cardiac responses, including 6 (11%) CR and 19 (36%) VGPR, and 25/42 (60%) had renal responses, including 5 (12%) CR and 10 (24%) VGPR. After a median follow up of 37.6 months (range, 3.0–89.0), 47 (61%) maintained the response without further therapy, 21 (27%) had two lines, and 9 (12%) had three or more lines. Among 30 patients requiring next-line therapy, 20 had t(11;14) and received Venetoclax. Median EFS was 41.9 months (95% CI, 18.9–64.9), median TTNT was 58.9 months (95% CI, 23.4–94.3), and median OS was not reached. At 2 years, the EFS rate was 58.3%, and 64.5% had not required next line treatment. In multivariate analysis, t(11;14) was an independent predictor for shorter TTNT (HR 2.55, 95% CI 1.08–6.01, P = 0.033) but not for OS. Gain 1q was not associated with TTNT but appeared adversely associated with OS in univariate analysis (HR 3.11, 95% CI 0.76–12.4, P = 0.091); this association lost significance in multivariate analysis. Conclusions: Dara-VCD was an effective frontline therapy with 79% patients achieving ≥ VGPR with frequent organ responses. However, one third of patients required second line therapy, more often in patients with t(11;14). Despite the association of t(11;14) with shorter TTNT, OS does not differ, perhaps associated with Venetoclax. Gain 1q appears to be an adverse prognostic factor warranting further investigation. For patients with gain 1q at relapse, treatments such as bispecific antibodies, MEL SCT or CAR-T cell therapy should be considered. Baseline characteristics. Characteristics Results (n = 77)n (%) Median age (IQR) 67 (62–71) Sex, male 47 (61%) Involved light chain, lambda 57 (74%) Cytogenetics  t (11;14) 36 (47%)  gain 1q 11 (14%)  hyperdiploidy 10 (13%)  del 13q 5 (6%)  Cardiac stage, Mayo 04 68  I 7 (10%)  II 22 (32%)  IIIa 26 (38%)  IIIb 13 (19%)  Renal stage 54 (n = 75)  I 13 (24%)  II 29 (54%)  III 12 (22%)