ASCT Remains Significant Upfront Option in AL Amyloidosis

Morie A. Gertz, MD

In a 20-year observational study, investigators at Mayo Clinic Rochester found that autologous stem-cell transplantation (ASCT) improved overall survival (OS) and reduced treatment-related mortality in patients with immunoglobulin light chain (AL) amyloidosis.

Investigators retrospectively reviewed data on 672 consecutive patients receiving ASCT for AL amyloidosis from March 1996 to August 2016. Patients were then by date of transplantation (cohort 1, 1996-2002 [n = 124]; cohort 2, 2003-2009 [n = 302]; and cohort 3, 2010-2016 [n = 246]).

Across the entire study population, the median OS was 122 months, and the researchers found that results improved over time. Median OS was not reached for patients transplanted from 2010 to 2016, compared with 120 months for the 2003-2009 cohort, and 75 months for the 1996-2002 group (P <.001). Hematologic response was higher in cohort 3 (84%) compared with cohort 2 (79%) and cohort 1 (69%; P = .002).

All-cause mortality through 100 days after transplantation was 7.4% for the entire cohort. Rates of all-cause mortality improved from 14.5% in cohort 1 to 8.6% in cohort 2, and 2.4% in cohort 3 (P <.001).

“Our data show excellent results with ASCT for patients with AL amyloidosis and a marked reduction in toxicity over time,” corresponding author Morie A. Gertz, MD, oncologist and chair of internal medicine at Mayo Clinic Rochester, and colleagues wrote. “Our results contrast with those of the only randomized trial of ASCT in AL amyloidosis published a decade ago.”

“ASCT is a highly effective therapy for AL amyloidosis. The improved survival and markedly reduced treatment-related mortality in eligible patients indicate that this will remain an important first-line option even in the era of treatment approaches that use novel agents,” added Gertz et al.

Investigators chose this time period to allow for assessment of changes in patient characteristics, treatment practices, and outcomes over time. Gertz et al wrote that the introduction of novel agents, especially bortezomib (Velcade) in 2005, has made physicians much more willing to perform ASCT on high-risk patients.

“The availability of these agents before transplant may have helped improve organ function to reduce toxicity from ASCT,” they wrote. “Second, our understanding of high-risk disease features in AL amyloidosis has significantly improved over time.”

Patients in cohort 3 were slightly older (60 years) than those in cohorts 2 (58 years) and 1 (54 years). Men made up the bulk of the overall cohort. Rates of cardiac and neurologic involvement were not significantly different across time periods.

The median N-terminal prohormone brain natriuretic peptide was 490 pg/mL in cohort 1 (n = 61), 657 pg/mL in cohort 2, and 453 pg/mL in cohort 3 (P = .21). Fewer patients presented with renal or hepatic involvement in cohort 3, and fewer patients in cohort 3 (9%) had extensive organ involvement, defined as more than two organs involved, than cohorts 2 (18%) or 1 (19%; P <.001).

More than 65% of patients in all 3 cohorts received plasma-cell clone with lambda light chain restriction. Patients in cohorts 3 (41%) and 2 (39%) were less likely to have more than 10% bone marrow plasma cells than cohort 1 (53%; P = .03).

While patients in the most recent cohort were more likely to respond to treatment, the rates of complete response (CR) remained similar over time: 39% for cohort 3, 43% for cohort 2, and 32% for cohort 1.

Median follow-up of survivors was 78 months (range, 43-127). Median OS by Mayo stage 2012 was 187 months for stage I, 161 months for stage II, 65 months for stage III, and 100 months for stage IV (P <.001).

Hematologic response has been shown to be a strong predictor of outcome in patients with amyloidosis. Median OS was 187 months for patients achieving a CR, 105 months for very good partial response, 74 months for partial response, and 16 months for nonresponders (P <.001).

The percentage of patients receiving full-intensity conditioning increased from 65% and 66% in cohorts 1 and 2 to 76% in cohort 3 (P = .001). Most patients (69%) received full-intensity melphalan (200 mg/m²), while 30% received reduced-intensity with <200 mg/m² of melphalan. Of the reduced-intensity group, 87% received 140 mg/m2 of melphalan. Six patients (1%), all in cohort 3, received conditioning with carmustine, etoposide, cytarabine, and melphalan (BEAM).

The number of patients receiving full-intensity conditioning was greater in cohort 3 (76%) compared with cohorts 2 (66%) and 1 (65%).

Patients who received conditioning with full-intensity melphalan had a longer median OS compared with patients who received reduced-intensity conditioning (140 mg/m²; 169 vs 54 months; P <.001).

Sidiqi MH, Aljama MA, Buadi FK, et al. Stem cell transplantation for light chain amyloidosis: decreased early mortality over time [published online March 20, 2018]. J Clin Oncol. doi.org/10.1200/JCO.2017. 76.9554.