A Validated Composite Organ and Hematologic Response Model for Early Assessment of Treatment Outcomes in Light Chain Amyloidosis

Newly diagnosed AL amyloidosis patients were evaluated to develop a model for early assessment of treatment benefit at 6 months, integrating both hematologic (HR) and organ response (OR) assessment (testing cohort, Mayo: n = 473; validation cohort, Pavia: n = 575). Multiple OR were assessed as follows: All OR (AOR): response in all organs, mixed OR (MOR): response in some organs, no OR (NOR)]. AOR rates at 6 months improved with deepening HR; complete response (CR; 38%, 35%), very good partial response (VGPR; 30%, 26%), and partial response (PR; 16%, 21%), respectively. A composite HR/OR (CHOR) model was developed using incremental scoring based on hazard ratios with scores of 0-3 for HR (0-CR, 1-VGPR, 2-PR, 3-no response) and 0-2 for OR (0-AOR, 1-MOR, 2-NOR). Patients could be divided into two distinct CHOR groups (scores 0-3 and 4-5), with median OS in group 1 and group 2: Not reached vs. 34 months, p \u3c 0.001 [Mayo] and 87 vs. 23 months, p \u3c 0.001 [Pavia]. In conclusion, we developed a model that can assess multiple organs concurrently, and integrate both HR and OR assessments to determine early clinical benefit with treatment, which may be used as a surrogate end-point in trials and to compare outcomes with different therapies

Serial measurements of circulating plasma cells before and after induction therapy have an independent prognostic impact in patients with multiple myeloma undergoing upfront autologous transplantation

Circulating plasma cells at diagnosis, prior to auto-transplant and at relapse have a negative impact on survival in multiple myeloma. However, the impact of kinetics of circulating plasma cells along the course of illness has not been defined. We have analyzed 247 newly diagnosed multiple myeloma patients undergoing early auto-transplant who had paired evaluation of circulating plasma cells at diagnosis and pre-transplant by 6-color flow cytometry. A total of 117 patients had no detectable circulating plasma cells at both time points (CPC−/−), 82 had circulating plasma cells at diagnosis followed by complete eradication after induction (CPC+/−) and 48 had circulating plasma cells at transplant, including persistence of cells (CPC+/+; n=45) or emergence of new cells (CPC−/+; n=3) after induction. The rate of post-transplant stringent complete response was 32% in the CPC−/−, 30% in CPC+/− and 12% in CPC+/+ or −/+ groups (P=0.018). At a median follow up of 58 months from transplantation, the median progression-free survival in the 3 respective groups were 30, 24 and 14 months, and the 5-year overall survival rates were 83%, 70% and 43% (

Plasma cell proliferative index predicts outcome in immunoglobulin light chain amyloidosis treated with stem cell transplantation

The plasma cell proliferative index provides an insight into plasma cell biology in plasma cell disorders and is an important prognostic marker in myeloma and smoldering myeloma. We analyzed the prognostic impact of the plasma cell proliferative index in 513 patients with systemic immunoglobulin light chain (AL) amyloidosis undergoing stem cell transplantation at the Mayo Clinic between 1st January 2003 and 31st August 2016. Two cohorts were identified according to Low or Elevated plasma cell proliferative index. Patients with an Elevated plasma cell proliferative index had more cardiac involvement (56% vs. 44%; P=0.01), less renal involvement (55% vs. 70%; P=0.001), and were more likely to have 10% or over bone marrow plasma cells (58% vs. 32%;

Activity of pomalidomide in patients with immunoglobulin light-chain amyloidosis

Immunoglobulin light-chain (AL) amyloidosis is a rare, incurable plasma cell disorder. Its therapy has benefited immensely from the expanding drug armamentarium available for multiple myeloma. Pomalidomide in combination with weekly dexamethasone (Pom/dex) is active among patients with relapsed myeloma. In the present study, we explored the Pom/dex combination in patients with previously treated AL. Patients were eligible for this prospective phase 2 trial if they had had at least one prior regimen and if they had reasonably preserved organ function. Patients were treated with oral Pom/dex. Thirty-three patients were enrolled. The median age was 66 years. Median time from diagnosis to on-study was 37 months. Eighty-two percent had cardiac involvement. The confirmed hematologic response rate was 48%, with a median time to response of 1.9 months. Organ improvement was documented in 5 patients. The median overall and progression-free survival rates were 28 and 14 months, respectively; the 1-year overall and progression-free survival rates were 76% and 59%, respectively. There was a discordance between the hematologic response and the N-terminal probrain natriuretic peptide response. The most common grade 3-5 adverse events, regardless of attribution, were neutropenia and fatigue. We conclude that pomalidomide appears to be a valuable drug covering an unmet clinical need in patients with previously treated AL. The trial is registered at www.clinicaltrials.gov as NCT00558896. (Blood. 2012;119(23): 5397-5404

Hematopoietic recovery kinetics predicts for poor CD34+ cell mobilization after cyclophosphamide chemotherapy in multiple myeloma

Autologous stem cell transplantation is an important part of therapy in patients with multiple myeloma. Some patients fail to collect the desired number of stem cells while others require multiple apheresis to reach the desired apheresis target. The aim of this study was to determine the predictive factors and if the hematopoietic kinetics of recovery were predictive for outcome of stem cell mobilization in cyclophosphamide + growth factor (CY-GF) mobilized patients. Three hundred and ninety six consecutive CY-GF mobilization attempts between January 2000 and December 2009 at Mayo Clinic, Rochester, MN were analyzed. Patients were divided into three groups: optimal (>5 x 106 CD34/kg), suboptimal (25 x 106 CD34/kg) and poor (10/mu L predicted for efficiency of collection and the interval between recovery of WBC>1 post-CY to PB CD34+ cells>10 was shorter in the optimal collection groups. These findings suggest that for patients with a PB CD34+ cell count below 10/mu L on Day 13 following CY or 1 day after the WBC>1 x 109/L, addition of plerixafor may be helpful to salvage the mobilization attempt. Am. J. Hematol., 2012. (C) 2011 Wiley Periodicals, Inc