P884: POTENTIAL BENEFIT OF POST-TRANSPLANT DOXYCYCLINE IN AL ACHIEVING HEMATOLOGICAL RESPONSE AFTER AUTOLOGOUS STEM CELL TRANSPLANT – LONG TERM FOLLOW UP

Abstract

Background: Systemic light chain (AL) amyloidosis is a clonal plasma cell disorder characterized by multiorgan deposition of fibrils composed of misfolded immunoglobulin light chains. Current treatment strategies targeting the plasma cell clone do not result in immediate organ recovery, and thus effective fibril-directed therapies are needed. Doxycycline has been shown to disrupt amyloid fibril formation in preclinical models. In 2012, we reported initial results on the impact of posttransplant prophylaxis with doxycycline using data from 445 AL amyloidosis patients; prophylaxis with doxycycline was associated with improved survival compared to penicillin in those achieving hematologic response. Since then, few studies have evaluated doxycycline use in AL amyloidosis, mainly in combination with induction chemotherapy, with mixed results. We provide here updated results on outcomes of AL amyloidosis patients who received doxycycline prophylaxis post autologous stem cell transplantation (ASCT) in our institution. Aims: To evaluate the impact of doxycycline use for post-ASCT antimicrobial prophylaxis on survival in AL amyloidosis patients. Methods: We included 553 patients who underwent ASCT from July 1996 to June 2014. We excluded patients who died within 100 days of ASCT. Doxycycline 100 mg daily was substituted for penicillin prophylaxis in patients with penicillin allergy; since 2013, doxycycline has become the standard for prophylaxis in AL amyloidosis at our institution. Prophylaxis was typically continued for a year after ASCT. Antibiotic type was determined by review of medical records. The Kaplan-Meier method was used to estimate time to next treatment (TTNT) and overall survival (OS), both measured from the time of transplant; curves were compared using the log-rank test. Results: Median age was 59 and 60% were male. The median time from diagnosis to ASCT was 4 months; 90% had early ASCT (within 1 year of diagnosis) and 57% received upfront ASCT without prior induction. Penicillin was used for prophylaxis in 67% (372 patients); the rest received doxycycline. Hematologic and organ response rates were similar in the 2 groups. Median follow up from ASCT was 10.5 vs. 13.6 years in the doxycycline and penicillin groups, respectively. Among patients with early ASCT, TTNT was 5.5 (95%CI: 4.2-8.1) vs. 5.8 (95%CI: 4.7-6.8) years, respectively (P=0.95). Median OS was 12.0 (95%CI: 11.0-19.6) vs. 11.0 (95%CI: 9.6-12.7) years, respectively (P=0.17); 5- and 10-year OS rates were 81% vs. 75% and 62% vs. 54% in the doxycycline and penicillin groups, respectively. Among patients with day 100 hematologic response, there was a non-statistically significant trend towards improved OS with doxycycline, but no difference in those without hematologic response: median OS with doxycycline vs. penicillin was 21.1 vs. 14.6 years in patients with day 100 dFLC <4 mg/dL (P=0.18) Figure 1a. In patients with normal day 100 FLCr, median OS was NR vs. 12.8 years, respectively (P=0.10) Figure 1b. There was no difference between the 2 groups when OS was stratified by Mayo 2012 stage (1-2 vs 3-4), number of involved organs (1 vs. >1), ASCT period (before or after 2012), or pre-ASCT induction (Yes vs. No). Image:Summary/Conclusion: After 13 years of follow up we observed a trend towards improved OS with doxycycline as post-ASCT prophylaxis in patients who achieve a hematological response. Prospective studies are needed to elucidate whether doxycycline improves outcomes in AL amyloidosis and identify the optimal dose, duration, timing, and the subset of patients likely to benefit.