Treatment with bortezomib‐based regimens improves overall response and predicts for survival in patients with primary or secondary plasma cell leukemia: Analysis of the Greek myeloma study group

Plasma cell leukemia (PCL) is a rare and aggressive plasma cell disorder, with poor outcome. Bortezomib‐based regimens (BBR) are highly effective in myeloma, but there is limited information about their efficacy and safety in PCL. Thus, we retrospectively collected data from 42 consecutive PCL patients (25 with primary PCL‐pPCL and 17 with secondary PCL‐sPCL) to explore the role of BBR in this entity. BBR were administered in 29 of 42 patients, while 6 of 25 patients with pPCL underwent autologous transplantation. Objective response (≥partial response) was significantly higher in patients treated with BBR versus conventional therapies (69% vs. 30.8%, P = 0.04); 27.5% of patients treated with BBR achieved at least very good partial response (vgPR). The highest ORR was observed in pPCL patients treated with BBR (88.9%; ≥vgPR: 33.3%). In BBR‐group, grade 3 of 4 hematological, neurological and renal toxicity and neutropenic infections were observed in 41.4%, 7%, 3.4%, and 31%, respectively. With a median follow‐up of 51 months, median overall survival (OS) for patients treated with BBR versus conventional therapies was 13 versus 2 months (P < 0.007). Median OS of patients with pPCL and sPCL treated with BBR was 18 and 7 months, respectively (P < 0.001). In the multivariate analysis normal PLTs, treatment with BBR and high quality response were the only powerful predictors for survival. Our study carrying the longest reported median follow‐up, demonstrated that treatment of PCL with BBR induces high response rates and prolongs survival over conventional therapies, regardless of additional autologous transplantation rescue or established high risk features, with manageable toxicity. Am. J. Hematol. 89:145–150, 2014. © 2013 Wiley Periodicals, Inc.     

Hyalinosis cutis et mucosae: gingival involvement

Hyalinosis cutis et mucosae (lipoid proteinosis, Urbach-Wiethe disease) is a rare syndrome with autosomal recessive inheritance. The disease is characterized by diffuse deposition of a hyaline-like substance in the dermis, the submucosal connective tissue and various internal organs. The oral mucosa of affected people becomes nodular and thickened, with primary involvement of the labial, buccal and palatal mucosa, posterior tongue, and lingual frenulum. We report the case of a 66-year-old man with hyalinosis cutis et mucosae who presented with gingival hyperplasia due to diffuse deposition of hyaline-like material, and discuss the diagnostic significance of the microscopic findings of the gingival tissues. The present clinical features are also compared to those of the same patient at the age of 38 years.     

Re‐evaluation of prognostic markers including staging,serum free light chains or their ratio and serum lactate dehydrogenase in multiple myeloma patients receiving novel agents

International Staging System (ISS), serum free light chain ratio (sFLCR) and lactate dehydrogenase (LDH) are well known, easily assessed independent prognostic indicators of outcome in multiple myeloma (MM). The purpose of the study was to re‐examine the prognostic contribution of these variables in a multicenter setting with special attention to MM patients treated with autologous stem cell transplantation (ASCT) or novel agents (NA). Three hundred and five symptomatic newly diagnosed MM patients were retrospectively studied. Twenty‐seven per cent, 32% and 41% were in ISS stages 1, 2, and 3, respectively. Fifty‐six per cent of them presented kappa light chain monoclonality; median sFLCR was 27.04 (0.37–1.9 × 10⁵) and 47.97 (0.26–2.3 × 10⁷) for kappa patients and lambda patients, respectively; patients with sFLCR above median constituted the high sFLCR group. Thirty‐one per cent of patients had increased LDH. As first line treatment, 55.7% received conventional treatment and 44.3% NA. After induction, 24% underwent ASCT, whereas 76% received NA at any line, either bortezomib (82.5%), thalidomide (48%) or lenalidomide (27%). When the 305 patients were analyzed together, staging, high sFLCR and abnormal LDH were predictive of survival. The same was true for patients that never received NA, whereas neither high sFLCR nor abnormal LDH constituted adverse factors in patients that received NA frontline. In the last group of patients, no difference was observed between ISS stages 2 and 3. The median 5‐year survival of patients that never received NA versus those who did frontline was 29% vs 47%, 7% vs 52% and 24% vs 40% in patients with abnormal LDH, high sFLCR and ISS stage 3, respectively (p = 0.03, p < 0.00001 and p = 0.035). In conclusion, patients gaining the most from NA are those with an aggressive disease as reflected by advanced stage, abnormal LDH and high sFLCR. In addition, the adverse impact of these three variables is obscured by NA. Copyright © 2012 John Wiley & Sons, Ltd.     

Clinical Characteristics and Outcome of Primary Systemic Light-Chain Amyloidosis in Greece

Background:Primary systemic light-chain (AL) amyloidosis is characterized by the deposition of immunoglobulin light chain–derived amyloid fibrils in various tissues leading to multiorgan dysfunction.Patients and Methods:In order to define characteristics, treatment, and outcome of Greek patients with AL amyloidosis, we analyzed 112 unselected patients with AL from several hospitals.Results:The heart was involved in 59% of patients and kidneys in 71%. Patients were treated with several different treatment regimens; high-dose dexamethasone-based regimens were used as primary treatment in 43% and melphalan-based regimens in 37%, while 12% received up-front bortezomib with dexamethasone. A hematologic response to first-line therapy was documented in 50% (complete response, 14.5%), and organ responses were observed in 25% of patients, the latter being strongly associated with achievement of hematologic response. Median overall survival was 34.2 months and was independently affected by heart involvement, creatinine, age, involvement of ≥ 2 organs, and bone marrow plasmacytosis > 30%. In patients with cardiac involvement, advanced age and extended bone marrow plasmacytosis were associated with an even worse outcome, while for patients without heart involvement, only bone marrow plasmacytosis was independently associated with survival. Hematologic response was associated with improved survival in patients with heart involvement but mostly in patients with less bone marrow infiltration.Conclusion:In this first series of patients from Greece with AL amyloidosis, disease features and outcome appeared similar to those reported from tertiary centers. Heart involvement and bone marrow plasma cell infiltration comprise adverse prognostic factors but also indicate the heterogeneity of the disease and the need for individual treatment approaches.     

A phase 1/2 study of lenalidomide with low-dose oral cyclophosphamide and low-dose dexamethasone (RdC) in AL amyloidosis

In this phase 1/2 study, we explored the feasibility and activity of an oral regimen of lenalidomide with low-dose dexamethasone and low-dose oral cyclophosphamide (RdC) in patients with primary systemic light chain amyloidosis. RdC was given for up to 12 cycles in prespecified cohorts at escalated doses: 13 patients were treated in phase 1 and 24 in phase 2; 65% were previously untreated, and most had renal and/or cardiac involvement and elevated cardiac biomarkers. Lenalidomide 15 mg/d and cyclophosphamide 100 mg/d were further evaluated in phase 2. On intention to treat, 20 (55%) patients achieved a hematologic response, including 3 (8%) complete remissions. Hematologic responses were seen at all dose levels and in 4 of 5 patients who had received bortezomib previously. An organ response was recorded in 22% of patients on intention-to-treat and in 40% of patients who survived at least 6 months. The median time to progression was 10 months and the 2-year survival was 41%. Fatigue, nonneutropenic infections, and rash were the most common toxicities. The results of the present study show that RdC is an oral regimen with activity in primary systemic light chain amyloidosis and may be an additional treatment option, especially for patients with preserved organ function or for patients who cannot receive or who relapse after bortezomib. This study is registered at www.clinicaltrials.gov as NCT00981708.     

Prognostication in Young and Old Patients with Waldenström's Macroglobulinemia: Importance of the International Prognostic Scoring System and of Serum Lactate Dehydrogenase

We analyzed 232 patients with previously untreated, symptomatic WM, of whom 10% were ≤ 50 years of age and 21% were > 75 years of age. Disease features and response to treatment were similar among age groups. Patients > 75 years of age had significantly shorter survival (OS; 53 months vs. 113 months for those > 50–75 years vs. not reached for patients ≤ 50 years of age; P < .001). Despite the fact that 33% of elderly patients died of causes unrelated to WM, disease-specific survival (DSS) was 72 months for patients > 75 years, 120 months for those > 50-75 years and not reached for patients ≤ 50 years (P = .001). International Prognostic Scoring System for WM (IPSSWM) could discriminate 3 risk groups with significantly different OS or DSS. The addition of elevated serum lactate dehydrogenase in the IPSS improved the ability of IPSS to identify a group of patients with a significantly worse outcome (median survival, 55 months).