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Publications
Publications (80)
Patients with multiple myeloma who have relapsed after or become refractory to lenalidomide in early treatment lines represent a clinically important population in need of effective therapies. The safety and efficacy of pomalidomide, low-dose dexamethasone, and daratumumab was evaluated in lenalidomide-pretreated patients with relapsed or refractor...
Patients with relapsed/refractory multiple myeloma (RRMM) for whom the benefits of lenalidomide have been exhausted in early treatment lines need effective therapies. In cohort A of the phase 2 MM‐014 trial, we examined the safety and efficacy of pomalidomide plus low‐dose dexamethasone immediately after lenalidomide‐based treatment failure in pati...
8025
Background: Treatment (Tx) of RRMM is complex and requires evaluation of disease and patient (pt) factors to maximize efficacy and minimize toxicity. HRQoL has become an important aspect of MM Tx, as survival has improved with therapeutic advances. Results of the ongoing phase 2 MM-014 trial (NCT01946477) have demonstrated that pomalidomide (P...
BACKGROUND
Lenalidomide (LEN) until progressive disease (PD) is an established treatment (Tx) in newly diagnosed and relapsed and/or refractory multiple myeloma (RRMM); thus, patients (pts) for whom the benefit of LEN has been exhausted are a clinically relevant population. However, LEN-refractory pts have typically been excluded from recent clinic...
Background: Multiple myeloma clinical trial CC-4047-MM-014 (NCT01946477) is a Phase II study designed to test the safety and efficacy of pomalidomide and low-dose dexamethasone alone (arm A) or in combination with daratumumab, an anti-CD38 antibody, (arm B) subjects with relapsed or refractory multiple myeloma who have received a first or second li...
Background:
Multiple myeloma (MM) is characterized by the secretion of monoclonal protein by malignant plasma cells in the vast majority of cases. We identified and analyzed patterns of disease relapse and progression associated with disappearance of the paraprotein ("nonsecretory [NS] escape"), or conversion from production of intact Ig molecule...
8027
Background: Recent trials of triple therapy in 2L and third-line (3L) Tx excluded pts refractory to LEN. This is not reflective of standard of care in first line and 2L where LEN is given until progressive disease (PD). MM-014 enrolled pts with RRMM and 2L LEN-based Tx failure. Here we report results only from cohort A of pts receiving POM + L...
e19504
Background: Strategies for optimizing the collection of peripheral blood stem cells (PBSC) for autologous stem cell transplant (ASCT) in patients with multiple myeloma (MM) vary among transplant centers, and include the use of G-CSF alone or in combination with plerixafor, or mobilization chemotherapy + G-CSF. In 2010, we started using “upfr...
Objective
There is a growing body of evidence that combining radiotherapy with ipilimumab might improve the survival and response rates in patients with metastatic melanoma. However, the patient and treatment variables that predict for improved outcomes have not been well defined. Methods
We conducted a retrospective analysis of 69 patients treated...
Plasma cell neoplasms are characterized by the proliferation of monoclonal plasma cells and include a spectrum of disorders with different clinical manifestations. Multiple myeloma (MM) is the second most common hematological malignancy and recent studies have indicated that almost all cases of MM are preceded by a precursor state of monoclonal gam...
There is a growing body of evidence supporting the synergistic roles of radiotherapy and immunotherapy in the treatment of malignancy. Published case studies of the abscopal effect have been reported with the use of ipilimumab and radiotherapy in metastatic melanoma, but evidence supporting the routine use of this combination of therapy is limited....
Background:
Disease-specific skin lesions are rare in patients with multiple myeloma (MM).
Objective:
We sought to further characterize the clinical and pathologic features of patients with cutaneous involvement with MM.
Methods:
We identified 13 patients with cutaneous lesions of MM.
Results:
Cutaneous lesions consisted of pink, red, and vi...
Locoregional nodal recurrence of urothelial cell carcinoma of the bladder or upper tract can occur after definitive surgical management as the solitary site of metastasis. This may be related to the extent of the lymphadenectomy done at the time of the initial surgical extirpation of the cancer. Historically, lymph node dissection has been the main...
Abstract/Summary We report three cases of durable complete response (CR) in patients with BRAF-mutated metastatic melanoma who were initially treated unsuccessfully with sequential immunotherapies (high dose interleukin 2 followed by ipilimumab with or without concurrent radiation therapy). After progression during or post immunotherapy, these pati...
Immunomodulatory drugs (IMiDs) currently used in the treatment of multiple myeloma, are thalidomide, lenalidomide and pomalidomide. One of the most common side effects of thalidomide is neurotoxicity, predominantly in the form of peripheral neuropathy. We report 6 cases of significant central neurotoxicity associated with IMiD therapy. Treatment wi...
Radiation therapy (RT) is a treatment modality traditionally used in patients with multiple myeloma (MM), but little is known regarding the role and effectiveness of RT in the era of novel agents, i.e., immunomodulatory drugs and proteasome inhibitors.
We retrospectively reviewed data from 449 consecutive MM patients seen at our institute in 2010-2...
Measurement of daily proteinuria in patients with amyloidosis is recommended at the time of diagnosis for assessing renal involvement, and for monitoring disease activity. Renal involvement is usually defined by proteinuria >500 mg/day. We evaluated the accuracy of the random urine protein-to-creatinine ratio (Pr/Cr) in predicting 24 hour proteinur...
Anti-MAG neuropathy is a very rare form of acquired polyneuropathy associated with IgM monoclonal gammopathy of undetermined significance (MGUS). We conducted a retrospective review of 194 consecutive MGUS patients seen at the Penn State Hershey Cancer Institute. We identified six patients among 37 (16 %) with IgM MGUS with anti-MAG neuropathy. Int...
Acute pancreatitis is a rare complication of chemotherapy agents. We describe the case of a patient with multiple myeloma who developed acute pancreatitis after treatment with bortezomib, a proteasome inhibitor commonly used in the treatment of this disease. We reviewed the available medical literature on this topic, and found other seven similar c...
Bone disease, characterized by the presence of lytic lesions and osteoporosis is the hallmark of multiple myeloma (MM). Stromal cell-derived factor 1α (SDF-1α) and its receptor, CXC chemokine receptor 4 (CXCR4), has been implicated as a regulator of bone resorption, suggesting that agents that can suppress SDF1α/CXCR4 signaling might inhibit osteoc...
Background
Bortezomib has been shown to produce an anabolic bone effect (increase bone ALP and osteocalcin) in relapsed/refractory patients. This study examined the bone anabolic effect in patients with smoldering multiple myeloma (SMM) who, with a historical median age of 67 years, have frequent evidence of osteopenia not associated with lytic bon...
e19502
Background: Asparaginase is a mainstay of the treatment for ALL depriving the malignant cells of asparagine leading to cell death. There are reports of asparaginase activity in non-ALL malignancies including CLL, NHL, and multiple myeloma. We developed a combination regimen with full dose PEG-Asparagase (O) together with low dose liposomal d...
7039
Background: There is no consensus among institutions for the optimal strategy of peripheral blood stem cell (PBSC) collection for autologous stem cell transplantation (ASCT) in patients with multiple myeloma (MM). Methods: We retrospectively analysed the outcomes of PSBC collection in MM patients using the following mobilization regimens: cycl...
The traditional method to quantify the immunoglobulin free light chains (FLCs) in patients with multiple myeloma (MM)is based on either their serum levels or on 24-hour urine collections. The latter method is cumbersome and ofteninaccurate, and serum levels are currently the preferred method for quantifying FLCs in MM. Scarce data exist on the FLCq...
Background:
Little is known regarding body weight changes in patients with multiple myeloma (MM) during the course of their disease, and the influence of obesity in the overall survival (OS) of patients affected by this cancer.
Methods:
We retrospectively collected clinical data from 318 MM patients, and analyzed their weight and body mass index (...
Multiple myeloma (MM) is a plasma cell malignancy and the second most common hematologic cancer. MM is characterized by the accumulation of malignant plasma cells within the bone marrow, and presents clinically with a broad range of symptoms, including hypercalcemia, renal insufficiency, anemia, and lytic bone lesions. MM is a heterogeneous disease...
4073
Background
Inhibition of histone deacetylase (HDAC) provides a novel approach for cancer treatment. Bortezomib and panobinostat are active agents in multiple myeloma (MM) and have a synergistic antimyeloma effect when used in combination. Both compounds have also shown anabolic bone effect.
Methods
We conducted a phase I exploratory study IV...
Despite significant treatment advances over the past decade, multiple myeloma (MM) remains largely incurable. In this study we found that MM cells were remarkably sensitive to the death-inducing effects of a new class of sangivamycin-like molecules (SLMs). A panel of structurally related SLMs selectively induced apoptosis in MM cells but not other...
There is little data comparing the activity and toxicity of donor lymphocyte therapy with granulocyte (G)-CSF-mobilized cells (G-donor lymphocyte infusion (DLI)) with the conventionally collected DLI (C-DLI) after allogeneic blood or marrow transplantation. We retrospectively evaluated 67 patients to compare the efficacy and toxicity of GCSF-mobili...
Plasma cell leukemia (PCL) is a rare hematologic malignancy with aggressive clinical and biologic features. Data regarding its prognosis with the use of the novel agents, i.e., the immunomodulatory drugs thalidomide and lenalidomide, and the proteasome inhibitor bortezomib, are limited. We retrospectively reviewed clinical outcomes, response to the...
Plasma cell leukemia (PCL) is a rare hematologic malignancy with aggressive clinical and biologic features. Data regarding its prognosis with the use of the novel agents, i.e., the immunomodulatory drugs thalidomide and lenalidomide, and the proteasome inhibitor bortezomib, are limited. We retrospectively reviewed clinical outcomes, response to the...
Little is known about the degree of pain experienced by patients undergoing a bone marrow aspiration and biopsy (BMAB).
To evaluate the effectiveness of several strategies aimed at reducing the pain score.
We conducted a retrospective analysis of 258 consecutive adult patients who underwent BMAB via 6 different approaches, the first 5 of which were...
8090
Background: Recent data from patients with multiple myeloma (MM) enrolled in randomized clinical trials have shown an increased incidence of second malignancies after treatment with lenalidomide, but the prevalence of second malignancies in the overall MM population is uncertain. Methods: We retrospectively analyzed the medical records of 320...
High-dose melphalan (HD-Mel) is considered the current standard of care among the preparative regimens used in autologous peripheral blood stem cell transplantation (SCT) for multiple myeloma (MM), but optimal time and schedule of administration is not defined. We retrospectively analyzed outcomes and toxicities of HD-Mel administered on day -2 vs....
s: AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics--Nov 12-16, 2011; San Francisco, CA
We previously reported the anti-tumor and anti-angiogenic activity of a new class of sangivamycin-like molecules (SLMs). In this study we aimed to further the preclinical development of these compounds by identifying tumor type...
Although the typical clinical manifestations of multiple myeloma (MM) are summarized by the CRAB symptoms (hypercalcemia, renal insufficiency, anemia, and bone lesions), a significant proportion of patients with MM present with a variety of other clinical manifestations. We conducted a study evaluating the presenting symptoms that led to the diagno...
We describe a case of multiple myeloma (MM) and secondary plasma cell leukemia (PCL) secreting IgE-kappa immunoglobulin. To our knowledge, only 2 cases of IgE-producing secondary PCL have been reported in the medical literature. In our patient, the only tumor marker available for monitoring the therapeutic response to chemotherapy and allogeneic st...
We report the case of a 57-year-old patient with multiple myeloma, characterized by extramedullary involvement of the rectum at presentation. Malignant plasma cells were found to produce carcinoembryonic antigen (CEA), a tumor antigen more commonly associated with rectal adenocarcinomas.
1212
Poster Board I-234
Background
The use of sirolimus (rapamycin) as primary immunosuppression for allogeneic blood and marrow transplantation is logical given its favorable anti-tumor and tolerance inducing properties.
Methods
After IRB approval, we analysed long term survival and predictive correlates in 92 patients receiving sirolimus based...
4329
The use of sirolimus (rapamycin) as an immunosuppressive agent after allogeneic hematopoietic transplantation is appealing given its antitumor and tolerance-inducing properties. Its safety and efficacy have been studied but are not completely understood in this patient population. We have compared GVHD prophylaxis with sirolimus together with...
4301
Introduction
Donor lymphocyte infusions (DLI) can reverse relapse of hematologic malignancy following allogeneic hematopoietic stem cell transplant (HSCT) in some cases. G-CSF is used to mobilize progenitor cells for transplantation and at our center excess cells have been cryopreserved and subsequently used as DLIs. Little is known regarding...
Medical literature provides only scarce data about the degree of pain experienced by patients undergoing a bone marrow aspiration and biopsy (BMAB), and little is known about the factors that can modify the perception of pain. In this study, we evaluated the effectiveness of a combination of analgesia and anxiolysis in reducing the pain score of pa...
The therapeutic use of thalidomide in patients with multiple myeloma is often complicated by the development of venous thromboembolism. The objective of the present study was to identify hypercoagulable states associated with development of venous thromboembolism in thalidomide-treated multiple myeloma patients. We screened 49 consecutive multiple...
High-dose melphalan is considered the current standard of care among the preparative regimens used in peripheral blood autologous SCT (ASCT) for multiple myeloma (MM). We report the results of a single ASCT in 79 MM patients using the BU/CY conditioning regimen, with BU 1 mg/kg p.o. or 0.8 mg/kg i.v. every 6 h x 16 doses, and CY 60 mg/kg per day i....
Autologous peripheral blood stem cell transplantation (ASCT) has been shown to improve survival in patients with multiple myeloma (MM). High-dose melphalan is considered the current standard of care among the preparative regimens used in ASCT for MM patients. We report the results of ASCT in 79 consecutive MM patients using a conditioning regimen w...
We report 24 cases of multiple myeloma (MM) with involvement of the gastrointestinal (GI) system. We found a strong association with high A lactate dehydrogenase levels, plasmablastic morphology, and A unfavorable karyotype. GI involvement at the time of initial diagnosis was much rarer than later in the course of the disease. The A median survival...
High-dose therapy with melphalan can prolong survival among patients with multiple myeloma. We assessed whether the addition of thalidomide, which has activity against advanced and refractory myeloma, would further improve survival.
Between October 1998 and February 2004, 668 patients with newly diagnosed multiple myeloma received two cycles of int...
To identify a correlation between metaphase cytogenetics and relapse after reduced intensity conditioning (RIC) allotransplant for patients with multiple myeloma, data on 60 patients (median age 52) who received grafts from a sibling (n = 49) or unrelated donor (n = 11) were analyzed. Fifty-three patients (88%) showed chromosomal abnormalities (CA)...
To assess the prevalence, time of onset, risk factors, and outcome of avascular necrosis (AVN) of bone in patients with multiple myeloma undergoing antineoplastic therapy.
A total of 553 consecutive assessable patients were enrolled onto a treatment protocol consisting of dexamethasone-containing induction chemotherapy, autologous stem-cell transpl...
Based on an index patient who responded to V 1.0 mg/m2 + T 100 mg upon progression on V alone and documented prior resistance to T, a phase 1–2 trial was initiated of the V+T combination in patients with advanced and refractory MM, 79% with a history of cytogenetic abnormalities (CA) including 57% pre-V, 81% with one and 52% with 2 prior transplant...
Background: MEL-ASCT is standard therapy for multiple myeloma (MM) but is associated with severe infections, at times life-threatening.
Objective: To determine the risk factors for severe infection (bacteremia, septic shock, colitis, pneumonia) following MEL - ASCT for MM.
Materials and Methods: 382 consecutive MM patients (pts) enrolled in our Tot...
TT 2 has completed accrual of 668 patients as of February 2004, of whom 323 were randomized to T. All patients received intensive reduction with VAD, DCEP, CAD, DCEP, melphalan-based tandem autotransplants; consolidation chemotherapy with DPACE; and interferon maintenance. T randomization data still blinded. We report, however, on the effect of tot...
Background: Total therapy III (TT-III) is designed to improve the outcome of newly diagnosed myeloma (MM) patients (pts), especially those presenting with unfavorable cytogenetics. Induction employs 2 cycles of V-DTPACE (Velade™, dexamethasone, thalidomide, cisplatin, adryamycin®, cytoxan®, etoposide) followed by tandem melphalan 200 mg/m2 autologo...
The variability in survival among patients with myeloma can range from months to >10 years. Patients at highest risk are best identified by the presence or absence of an abnormal karyotype found by conventional cytogenetics. However, this test only accounts for ~15% of the variability in outcome. Thus, many patients who present with no cytogenetic...
Velcade™ (Vel) has shown promising activity as single agent and, more recently, in combination with other antimyeloma agents (dexamethasone, thalidomide) in relapsed or refractory multiple myeloma. We have now explored the efficacy and safety of adding Adriamycin™ 2.5–10.0mg/m2 continuous infusion on days 1–4 and days 9–12 to Velcade™ 1.0 or 1.3 mg...
Symptomatic/progressive MM sometimes develops on the background of MGUS or progresses through a smoldering MM phase (SMM); other patients may have initially a solitary plasmacytoma of bone (SPC). This study examines the survival implications of pre-existing conditions such as MGUS (n=22), SMM (n=22) or SPC (n=20) among 668 enrolled in TT 2. TT 2 co...
Purpose: To assess the prevalence, time of onset, risk factors, and outcome of avascular necrosis (AVN) of bone in patients with multiple myeloma undergoing antineoplastic therapy.
Patients And Methods: We reviewed the medical records of 561 myeloma patients (553 evaluable) enrolled in a treatment protocol consisting of dexamethasone-containing ind...
Cardiovascular complications during the treatment of patients with multiple myeloma (MM) are not uncommon (10%) and the frequency clearly increases with the use of regimens containing thalidomide (T) in combination with glucocorticosteroids or chemotherapy especially adriamycin. Even with prophylactic anticoagulation, DVT still occurs in 10% of suc...
We have previously reported on the adverse prognostic implications m-CA, present in ~ 33% of newly diagnosed patients especially when involving del 13 (~ 20%). To overcome the proliferation dependency of m-CA, FISH has been applied detecting abnormalities in virtually all patients with MM; FISH 13, detected in ~ 50% has been associated with poor ou...
Background: CRP is an acute-phase reactant that increases rapidly in response to inflammation (including infection).
Objective: to assess the value of daily CRP level as a predictor of severe complications [pneumonia, bacteremia or severe mucositis (Grades 3–4, NCI Common Toxicity Criteria)] after MEL-ASCT for MM.
Patients and Methods: 199 MM patie...
A group of 256 newly diagnosed myeloma patients were enrolled in a phase III study that included 4 monthly cycles of induction chemotherapy and tandem transplant. All patients were randomized to either receive or not receive thalidomide. A total of 221 patients (86%) received no prophylactic anticoagulation (cohort I); 35 patients received low dose...
The aim of this study was to evaluate the role of [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET) imaging in the diagnosis of infection of implantable vascular catheters.
We evaluated six patients with haematological cancer and infection of their implantable vascular catheter and who underwent FDG PET imaging around the time of the...
To evaluate the role of high-dose melphalan and autologous transplant (AT) in reversing dialysis-dependent renal failure, 59 patients still on dialysis at the time of AT were analyzed. A total of 37 patients had been on dialysis < or =6 months. A 5-year event-free and overall survival rate of all patients after AT was 24 and 36%, respectively. Of 5...
Thalidomide has antiangiogenic properties and was found to be effective in patients with multiple myeloma (MM) when used in the setting of posttransplantation relapse. We have now analyzed risk factors associated with development of deep vein thrombosis (DVT) in a cohort of 535 patients treated with thalidomide with cytotoxic chemotherapy (VAD [vin...
The mechanism(s) by which acute promyelocytic leukemia (APL) cells acquire resistance to all-trans retinoic acid (ATRA) is poorly understood. We describe here an APL cell line, named NB4.306, that shows resistance to the anti-proliferative action of ATRA. This cell line is also operationally resistant to most ATRA-induced phenotypic modifications (...
Acute promyelocytic leukemia is a clonal expansion of hematopoietic precursors blocked at the promyelocytic stage. The differentiation block can be reversed by retinoic acid, which induces blast maturation both in vitro and in vivo. Acute promyelocytic leukemia is characterized by a 15;17 chromosome translocation with breakpoints within the retinoi...
