Chronic lymphocytic leukemia (CLL) is the most common type of leukemia in western countries. The association between CLL and glomerular disease (GD) is rare. The most frequent GD associated with CLL ...is membranoproliferative membranous glomerulonephritis (GN) (MPGN) (45%) types I and II, followed by membranous glomerulonephritis, with the same reports of immunotactoid glomerulopathy (ITG). We report a case of ITG diagnosed on kidney biopsy in a CLL patient and the response of renal parameters to drug treatment for CLL. The patient was treated with several lines of therapies with a good response.
Twice-weekly carfilzomib is approved at 27 and 56 mg/m
to treat relapsed multiple myeloma patients. In the phase III study ARROW, once-weekly 70 mg/m 2 carfilzomib prolonged the median ...progression-free survival of relapsed multiple myeloma patients in comparison with twice-weekly 27 mg/m
carfilzomib, without adding significant toxicity. Data were pooled from two phase I/II studies of newly diagnosed multiple myeloma patients who received nine induction cycles of carfilzomib (either 70 mg/m
once-weekly or 36 mg/m
twice-weekly), cyclophosphamide and dexamethasone, followed by carfilzomib maintenance. Overall, 121 transplant-ineligible patients with newly diagnosed multiple myeloma were analyzed (once-weekly, n=63; twice-weekly, n=58). We found no significant difference in median progression-free survival 35.7 months (95%CI: 23.7-not reached, NR)
35.5 months (95%CI: 24.3-NR); HR: 1.39;
=0.26 and 3-year overall survival 70% 95%CI: 59%-84%)
72% (95%CI: 60%-85%); HR: 1.27;
=0.5 between once-weekly and twice-weekly carfilzomib. From the start of maintenance, 3-year progression-free survival 47% (95%CI: 33%-68%)
51% (95%CI: 38%-70%); HR: 1.04;
=0.92 and overall survival 72% (95%CI: 58%-89%)
73% (95%CI: 59%-90%); HR: 0.82;
=0.71 were similar in the once-
twice-weekly carfilzomib. The rate of grade 3-5 hematologic (24%
30%;
=0.82) and non-hematologic (38%
41%;
=0.83) adverse events was similar in the two groups. Once-weekly 70 mg/m
carfilzomib as induction and maintenance therapy for newly diagnosed multiple myeloma patients was as safe and effective as twice-weekly 36 mg/m
carfilzomib and provided a more convenient schedule. The trials are registered at
: 01857115 (IST-CAR-561
and 01346787
IST-CAR-506).
Flow cytometry is a highly sensitive and specific approach for discriminating between normal and clonal plasma cells in multiple myeloma. Uniform response criteria after treatment have been ...established by the International Myeloma Working Group and the EuroFlow Group; however, the way in which flow cytometry data are reported has suffered from no collaborative or multicentre efforts. This study, involving 8 expert laboratories and 12 clinical hematology units of the Lazio region in Italy, aims to produce a uniform and shared report among the various Centres. From the pre-analytical phase to sample processing, data acquisition, analysis, and evaluation of the potential limitations and pitfalls of the entire process, the study reaches a final conclusion shared by laboratories and clinicians according to the most updated principles and recommendations. The aim was to identify the necessary data to be included in the clinical report by using multiple-choice questionnaires at every single stage of the process. An agreement of more than 75% of the laboratories was considered mandatory for the data to be included in the report. By ensuring the operational autonomy of each laboratory, this study provides a clear report that limits subjective interpretations and highlights possible bias in the process, better supporting clinical decision-making.
Lenalidomide-dexamethasone (Rd) is standard treatment for elderly patients with multiple myeloma (MM). In this randomized phase 3 study, we investigated efficacy and feasibility of ...dose/schedule-adjusted Rd followed by maintenance at 10 mg per day without dexamethasone (Rd-R) vs continuous Rd in elderly, intermediate-fit newly diagnosed patients with MM. Primary end point was event-free survival (EFS), defined as progression/death from any cause, lenalidomide discontinuation, or hematologic grade 4 or nonhematologic grade 3 to 4 adverse event (AE). Of 199 evaluable patients, 101 received Rd-R and 98 continuous Rd. Median follow-up was 37 months. EFS was 10.4 vs 6.9 months (hazard ratio HR, 0.70; 95% confidence interval CI, 0.51-0.95; P = .02); median progression-free survival, 20.2 vs 18.3 months (HR, 0.78; 95% CI, 0.55-1.10; P = .16); and 3-year overall survival, 74% vs 63% (HR, 0.62; 95% CI, 0.37-1.03; P = .06) with Rd-R vs Rd, respectively. Rate of ≥1 nonhematologic grade ≥3 AE was 33% vs 43% (P = .14) in Rd-R vs Rd groups, with neutropenia (21% vs 18%), infections (10% vs 12%), and skin disorders (7% vs 3%) the most frequent; constitutional and central nervous system AEs mainly related to dexamethasone were more frequent with Rd. Lenalidomide was discontinued for AEs in 24% vs 30% and reduced in 45% vs 62% of patients receiving Rd-R vs Rd, respectively. In intermediate-fit patients, switching to reduced-dose lenalidomide maintenance without dexamethasone after 9 Rd cycles was feasible, with similar outcomes to standard continuous Rd. This trial was registered at www.clinicaltrials.gov as #NCT02215980.
Ruxolitinib is approved for polycythemia vera (PV) patients after failure to previous cytoreductive therapy, based on durable results observed in phase 3 trials. We report a multicenter retrospective ...study demonstrating the efficacy and safety of ruxolitinib in real-life setting. Eighty-three patients were evaluated. Median follow-up was 24.5 months (IQR 14.0–29.3). At a 3-month response assessment, ruxolitinib provided significant benefit in reducing hematocrit (HCT) level (
p
< 0.001), phlebotomy requirement (
p
< 0.001), leucocytes (
p
= 0.044), and disease-related symptoms (
p
< 0.001). The exposure-adjusted rates (per 100 patient-years) of infectious complications, thromboembolic events, and secondary malignancies were 6.9, 3, and 3.7, respectively. Non-melanoma skin cancers (NMSC) were the most frequent (40%) SM type. Lymphoproliferative disorders were not detected. Five (6%) patients permanently discontinued ruxolitinib treatment and four (5%) evolved in myelofibrosis (MF), but none in acute leukemia. The rate of MF evolution per 100 patient-years of exposure was 2.8. In our experience, ruxolitinib confirmed its efficacy and safety outside of clinical trials.
High‐dose chemotherapy followed by autologous stem cell transplantation (auto‐SCT) is the standard treatment for young patient ≤65 years with multiple myeloma (MM). The role of auto‐SCT in elderly ...patients older than 70 years remains controversial in the era of novel agents and especially since the recent introduction of monoclonal antibodies (AbMo). In this study, we evaluated 12 patients with MM over 70 years old undergoing auto‐SCT (elderly graft cohort) in seven centers of GIMEMA Working Group Lazio. We compared the baseline characteristics, treatment and outcome with 97 MM elderly patients who did not receive auto‐SCT (nontransplant patients) from the same registry who were ≥ 70 years old, but did not undergo auto‐SCT. The median progression free survival (PFS) for graft versus no‐graft cohort was 56.4 versus 26.1 months, respectively. There was a trend for better PFS among graft compared to nontransplant patient (p = .1). On the other hand, the median overall survival for transplant versus nontransplant cohort was 107.6 versus 49.5 months (p = .02). Despite the small number of patients aged ≥70 years and ≤74 years, it seems that auto‐SCT is well tolerated, safe and effective. Therefore, we propose that it should be considered an important treatment option in the era of new drugs in elderly fit patients with MM.
Background:
Multiple myeloma is a plasma cell dyscrasia accounting for 1% of neoplastic diseases and is the second most common hematologic malignancy after lymphoma. Pulmonary arterial hypertension ...is characterized by increased blood pressure in the pulmonary circulation and the development of pulmonary vascular remodeling. Increased resistance in the pulmonary vessels strains the right ventricle, leading to right heart failure.
Aim:
To report a case of a 65-year-old man who presented in 2017 with immunoglobulin G–kappa multiple myeloma characterized by pulmonary arterial hypertension during carfilzomib and dexamethasone treatment that resolved after stopping therapy.
Discussion:
Pulmonary arterial hypertension represents one of the main problems of carfilzomib and dexamethasone treatment, especially in patients with predisposing conditions such as hypertension. Therefore, monitoring and management of patients starting therapy with carfilzomib remains a critical issue. Although cardiac and vascular related adverse events were not frequent, a preemptive strategy prior to initiating carfilzomib appears advisable, particularly in patients at risk.
Conclusion:
The mechanism responsible for cardiac and vascular events during carfilzomib therapy is unclear. This case report highlights that it is important to define at baseline the appropriate screening of patients undergoing carfilzomib therapy with specific monitoring and symptom management and that future large prospective controlled studies are needed to define the correct monitoring strategy in refractory and relapsed multiple myeloma and the potential mechanism of vascular events.
Patients with primary gastric lymphoma are at an increased risk of developing gastric cancer. Data on gastric precancerous lesions development in these patients are scanty. We assessed gastric ...precancerous lesions in a cohort of patients with primary lymphoma.
Data of patients with primary gastric lymphoma mucosa-associated lymphoid tissue (MALT)- lymphoma or diffuse large B-cell lymphoma (DLBCL) were analysed. Multiple (>10) biopsies were performed on gastric mucosa at each endoscopic control, beyond macroscopic lesions. Presence and distribution of intestinal metaplasia (IM) at baseline, the onset at follow-up, and progression through the stomach or transformation in the incomplete IM type were assessed. The onset of neoplastic lesions was recorded.
Data of 50 patients (mean age of 63.6 ± 10.7 years; M/F: 25/25), including 40 with MALT-lymphoma and 10 with DLBCL, with median follow-up of 30.5 months (range: 9-108) and a median of 6 endoscopic controls (range: 3-14) were evaluated. At entry, IM was present in 12 (24%), and it developed in other 22 (57.9%) patients at a median follow-up of 6 (range: 3-40) months. Overall, progression of IM was observed in 7 (21.2%) cases, including extension in the stomach (n=5) or transformation into the incomplete type (n=2). Low-grade dysplasia was detected in 4, and indefinite dysplasia in other 7 patients. In one patient, low-grade dysplasia had progressed to high-grade and gastric adenocarcinoma of the fundus.
Our data found a frequent onset and rapid progression of precancerous lesions on gastric mucosa of lymphoma patients. This observation could explain the increased incidence of metachronous gastric cancer in these patients.
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