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1.
Case Rep Oncol ; 17(1): 747-752, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39015635

RESUMEN

Introduction: Multiple myeloma (MM) is an incurable bone marrow (BM)-based cancer involving clonal plasma cells. Most patients show elevated levels of serum monoclonal protein (sMP) and kappa or lambda serum free light chains (sFLCs) at diagnosis. However, around 1-2% of patients, termed nonsecretory, do not produce these biomarkers. As the disease progresses, more patients may become unevaluable using conventional markers, requiring invasive and expensive procedures like BM biopsies and positron emission tomography-computed tomography (PET-CT) scans for assessment and highlighting the need for alternative methods to monitor disease progression. Case Presentation: We present a case report of an MM patient who developed nonsecretory disease during his second line of treatment when he complained of new rib pain; progressive disease was then confirmed on a PET-CT scan. The patient showed an increase in his serum B-cell maturation antigen (sBCMA) levels whereas his conventional myeloma markers did not detect disease activity (sMP remained undetectable and involved sFLC level was normal). After starting a new treatment regimen, his rib pain disappeared, PET-CT scan improved, and sBCMA levels decreased. Upon relapse, he developed increased rib pain with a rising sBCMA level; his conventional myeloma markers did not detect disease activity. After changing to a new regimen, his rib pain improved, and this was accompanied by a decrease in his sBCMA levels. Conclusion: Thus, this case exemplifies the potential for sBCMA to provide a non-invasive method for monitoring MM patients who develop nonsecretory disease.

2.
Target Oncol ; 19(3): 343-357, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38643346

RESUMEN

BACKGROUND: Ruxolitinib (RUX), an orally administered selective Janus kinase 1/2 inhibitor, has received approval for the treatment of myelofibrosis, polycythemia vera, and graft-versus-host disease. We have previously demonstrated the anti-multiple myeloma effects of RUX alone and in combination with the immunomodulatory agent lenalidomide (LEN) and glucocorticosteroids both pre-clinically and clinically. OBJECTIVE: This study aims to evaluate whether LEN can achieve clinical activity among patients with multiple myeloma progressing on the combination of RUX and methylprednisolone (MP). METHODS: In this part of a phase I, multicenter, open-label study, we evaluated the safety and efficacy of RUX and MP for patients with multiple myeloma with progressive disease who had previously received a proteasome inhibitor, LEN, glucocorticosteroids, and at least three prior regimens; we also determined the safety and efficacy of adding LEN at the time of disease progression from the initial doublet treatment. Initially, all subjects received oral RUX 15 mg twice daily and oral MP 40 mg every other day. Those patients who developed progressive disease according to the International Myeloma Working Group criteria then received LEN 10 mg once daily on days 1-21 within a 28-day cycle in addition to RUX and MP, which were administered at the same doses these patients were receiving at the time progressive disease developed. RESULTS: Twenty-nine subjects (median age 64 years; 18 [62%] male) were enrolled in this part of the study and initially received the two-drug combination of RUX and MP. The median number of prior therapies was six (range 3-12). The overall response rate from this two-drug combination was 31% and the clinical benefit rate was 34%. The best responses were 1 very good partial response, 8 partial responses, 1 minor response, 12 stable disease, and 7 progressive disease. The median progression-free survival was 3.5 months (range  0.5-36.2 months). The median time to response was 3.0 months. The median duration of response was 12.5 months (range 2.8-36.2 months). Twenty (69%) patients who showed progressive disease had LEN added to RUX and MP; all patients had prior exposure to LEN and all but one patient was refractory to their last LEN-containing regimen. After the addition of LEN, the overall response rate was 30% and the clinical benefit rate was 40%. The best responses of patients following the addition of LEN were 2 very good partial responses, 4 partial responses, 2 minor responses, 8 stable disease, and 4 progressive disease. The median time to response was 2.6 months (range 0.7-15.0 months). The median duration of response was not reached. The median progression-free survival following the addition of LEN was 3.5 months (range 0.3-25.9 months). CONCLUSIONS: For patients with multiple myeloma, treatment with RUX and MP is effective and well tolerated, and LEN can be used to extend the benefit of this RUX-based treatment. CLINICAL TRIAL REGISTRATION: This study is registered with ClinicalTrials.gov, NCT03110822, and is ongoing.


Asunto(s)
Lenalidomida , Metilprednisolona , Mieloma Múltiple , Nitrilos , Pirazoles , Pirimidinas , Humanos , Mieloma Múltiple/tratamiento farmacológico , Masculino , Lenalidomida/uso terapéutico , Lenalidomida/farmacología , Femenino , Anciano , Pirazoles/uso terapéutico , Pirazoles/farmacología , Nitrilos/uso terapéutico , Pirimidinas/uso terapéutico , Pirimidinas/farmacología , Persona de Mediana Edad , Metilprednisolona/uso terapéutico , Metilprednisolona/farmacología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Anciano de 80 o más Años , Progresión de la Enfermedad , Adulto
3.
Am J Clin Pathol ; 161(1): 16-23, 2024 Jan 04.
Artículo en Inglés | MEDLINE | ID: mdl-37611113

RESUMEN

OBJECTIVES: Data regarding bone marrow (BM) sampling and cytogenetic testing rates for identification of translocation (11q13;14q32) and their changes over time in a multiple myeloma (MM) population are limited. We analyzed these metrics at a clinic specializing in the treatment of MM. METHODS: A total of 760 BM aspirate samples from 351 patients were collected between August 2004 and October 2021. We analyzed BM sampling statistics, cytogenetic testing frequency, and the incidence rates for the t(11;14) translocation in a single clinic specializing in the treatment of MM. RESULTS: We report that most (54.4%) patients had only 1 aspirate collected; the main reason (64.6%) for BM collection was to confirm disease progression. Less than half (47.5%) of BM samples collected for evaluation of MM disease had cytogenetic testing, but the rates have markedly increased in recent years. Our data demonstrated an incidence rate of 19.3% for t(11;14). CONCLUSIONS: This report suggests that some patients may need to retest for this genetic aberration due to the possibility of false negatives and the potential benefit of identifying the t(11;14) marker for patients who may be candidates for a highly effective targeted therapy consisting of the BCL-2 inhibitor venetoclax.


Asunto(s)
Mieloma Múltiple , Humanos , Mieloma Múltiple/genética , Incidencia , Translocación Genética , Médula Ósea , Citogenética
4.
Target Oncol ; 18(5): 735-747, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37682503

RESUMEN

BACKGROUND: Progression-free survival (PFS) and overall survival (OS) of newly diagnosed multiple myeloma (MM) patients have been widely published in the clinical trials setting, but data published from real-world settings are limited. OBJECTIVE: We determined the survival and factors that predict outcomes among 161 unselected, newly diagnosed MM patients whose frontline therapy was started at a single clinic specializing in the treatment of this B-cell malignancy. PATIENTS AND METHODS: None of these patients underwent an autologous stem cell transplantation as part of their initial therapy and the population had a high proportion (35%) of cytogenetic high-risk patients. RESULTS: With a median follow-up of 42.7 months, the cohort had a median PFS of 22.8 months and a median OS of 136.2 months. The 1-, 3-, and 5-year survival rates were 97.5%, 85.3%, and 76.2%, respectively. These results are considerably better than those reported from patients enrolled in clinical trials and those from countries with national registries. Age <65 years predicted for a longer OS (p = 0.0004). Baseline serum B-cell maturation antigen (sBCMA) levels were also assessed and showed median and mean levels of 320.3 ng/mL and 551.1 ng/mL, respectively. Furthermore, patients with baseline sBCMA levels in the lowest quartile (≤136.2 ng/mL) showed a longer PFS (p = 0.0262). CONCLUSION: These results provide clinicians with a real-world understanding of the survival of unselected, newly diagnosed patients initiating therapy in a clinic specializing in the care of MM patients.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Mieloma Múltiple , Humanos , Anciano , Antígeno de Maduración de Linfocitos B , Trasplante Autólogo , Linfocitos B
5.
Br J Haematol ; 200(6): 722-730, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36482815

RESUMEN

Although Janus kinase (JAK) inhibitors have demonstrated efficacy for treating autoimmune disorders and myeloproliferative neoplasms, their efficacy in treating other types of cancer has not been clearly demonstrated. We evaluated oral ruxolitinib (15 mg twice daily) with oral methylprednisolone (40 mg every other day) for multiple myeloma (MM) patients with progressive disease who had received a proteasome inhibitor, lenalidomide, glucocorticosteroids and three or more prior regimens. All of the planned 29 patients had been enrolled with follow-up until 28 April 2022. Median lines of prior therapy were 6 (range 3-12). Cytogenetics and fluorescent in situ hybridization were evaluable in 28 patients; 9 (32%) and 17 (70%) patients showed high-risk cytogenetics and/or 1q+, respectively. The overall response rate was 31%. The median duration of response was 13.1 (range 2.8-22.0) months. Median progression-free survival rate was 3.4 (range 0.5-24.6) months, Overall, the treatment was well tolerated. The combination of ruxolitinib and methylprednisolone demonstrated significant clinical activity among previously heavily-treated MM patients, and responses were achieved among patients who had high-risk cytogenetics. This is the first clinical study to show activity of JAK inhibitors in combination with steroids for MM patients and expands the potential use of these drugs to those with cancers other than myeloproliferative neoplasms.


Asunto(s)
Mieloma Múltiple , Humanos , Mieloma Múltiple/tratamiento farmacológico , Metilprednisolona/uso terapéutico , Hibridación Fluorescente in Situ , Pirimidinas/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Dexametasona
6.
Hematol Oncol ; 40(5): 906-913, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-35946431

RESUMEN

Ruxolitinib with lenalidomide and dexamethasone shows anti-myeloma effects in vitro and in vivo. MUC1 leads to lenalidomide resistance in multiple myeloma (MM) cells, and ruxolitinib blocks its expression. Thus, ruxolitinib may restore sensitivity to lenalidomide. A phase I trial was conducted to determine the safety and efficacy of ruxolitinib with lenalidomide and methylprednisolone for patients with relapsed/refractory (RR)MM who had been treated with lenalidomide, steroids and a proteasome inhibitor and showed progressive disease at study entry. A traditional 3 + 3 dose escalation design was used to enroll subjects in four cohorts. Subjects received ruxolitinib twice daily, lenalidomide daily on days 1-21 of a 28 day cycle and methylprednisolone orally every other day. Primary endpoints were safety, clinical benefit rate (CBR) and overall response rate (ORR). Forty-nine patients were enrolled. The median age was 64 years and they had received a median of six prior treatments including lenalidomide and steroids to which 94% were refractory. No dose limiting toxicities occurred. The CBR and ORR were 49% and 36%, respectively. All responding patients were refractory to lenalidomide. Grade 3 or 4 adverse events (AEs) included anemia (17%), decreased lymphocyte count (15%), and hypophosphatemia (10%). Most common serious AEs included sepsis (9.8%) and pneumonia (7.8%). This Phase I trial demonstrates that a JAK inhibitor, ruxolitinib, can overcome refractoriness to lenalidomide and steroids for patients with RRMM. These results represent a promising novel therapeutic approach for treating MM. NCT03110822.


Asunto(s)
Mieloma Múltiple , Humanos , Persona de Mediana Edad , Lenalidomida , Mieloma Múltiple/tratamiento farmacológico
8.
Exp Hematol ; 111: 79-86, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35417741

RESUMEN

Identifying effective combination regimens is a high priority in multiple myeloma (MM), as most patients eventually become refractory to their current treatments. In this study, we investigated whether the proteasome inhibitor (PI) ixazomib could delay disease progression among patients who failed regimens containing another PI, bortezomib or carfilzomib. This phase 1/2, multicenter, open-label, nonrandomized study enrolled patients who were refractory to a previous regimen containing bortezomib or carfilzomib. Patients continued the other anti-MM drugs in the regimen at the same doses and frequencies. Patients with combination regimens with unknown maximum tolerated dose (MTD) of ixazomib were enrolled in phase 1, with ixazomib starting at 3 mg and then dose escalated to 4 mg. Patients on regimens with a known ixazomib MTD were enrolled in phase 2. Primary endpoints were overall response rate (ORR), clinical benefit rate (CBR), adverse events (AEs), and determination of maximum tolerated dose (MTD). Of the 46 patients enrolled, 39 were evaluable for efficacy. ORR and CBR were 12.8% and 17.9%, respectively. Ixazomib appeared to be well tolerated as a replacement for carfilzomib and bortezomib, with 23.9% of patients experiencing at least one grade ≥3 serious adverse event (SAE) and 37.0% experiencing at least one grade ≥3 AE. The most common grade ≥3 AEs were hyponatremia (8.7%), anemia (8.7%), dyspnea (8.7%), thrombocytopenia (6.5%), dehydration (4.3%), and pneumonia (4.3%). The results indicate that ixazomib is not an effective replacement for bortezomib or carfilzomib for patients with MM who have previously relapsed on other bortezomib/carfilzomib-containing regimens.


Asunto(s)
Mieloma Múltiple , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Compuestos de Boro , Bortezomib , Dexametasona/efectos adversos , Glicina/análogos & derivados , Humanos , Mieloma Múltiple/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Oligopéptidos
9.
Hematol Oncol ; 40(2): 243-248, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-34982491

RESUMEN

Previous retrospective studies have shown that serum B-cell maturation antigen (sBCMA) levels predict outcomes among patients with multiple myeloma (MM) undergoing new treatments. Specifically, baseline levels and changes during treatment of this protein predict both progression free survival (PFS) and overall survival. However, prospective studies are lacking evaluating sBCMA for determining outcomes among MM patients undergoing new treatments. Thus, we evaluated whether its baseline levels and changes during treatment in the amount of this serum marker predict outcomes among 38 relapsed/refractory MM patients treated with ruxolitinib, lenalidomide and methylprednisolone in a phase 1 trial. Patients with baseline sBCMA levels in the lowest three quartiles had longer PFS (median PFS 136 vs. 28 days; p < 0.0001). This was also shown for patients with baseline levels below the median (median PFS 140 vs. 77 days; p = 0.0225). PFS was shorter for patients whose sBCMA levels increased ≥25% through their first cycle (median PFS: 50 vs. 134 days, p = 0.0022), second cycle (median PFS: 50 vs. 141 days, p = 0.0273), and during the first three cycles of study treatment (median PFS: 50 vs. 220 days, p < 0.0001). No patient whose sBCMA increased ≥25% during cycle 1 responded whereas the majority (58%) of patients whose level increased <25% responded. This is the first prospective study to determine whether sBCMA levels predict outcomes for MM patients undergoing a non-BCMA directed treatment regimen and demonstrates that baseline levels and its changes during treatment predict PFS and the likelihood of responding to their treatment. These results add to the growing literature suggesting that this serum marker will be useful for determining outcomes for patients undergoing treatment for MM.


Asunto(s)
Antígeno de Maduración de Linfocitos B , Mieloma Múltiple , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Antígeno de Maduración de Linfocitos B/uso terapéutico , Dexametasona/efectos adversos , Humanos , Lenalidomida/uso terapéutico , Metilprednisolona/uso terapéutico , Nitrilos , Estudios Prospectivos , Pirazoles , Pirimidinas
10.
Leuk Lymphoma ; 63(4): 975-983, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-34818965

RESUMEN

High-risk multiple myeloma (MM) continues to have a poor prognosis and remains a therapeutic challenge. This phase 2 study evaluated the efficacy and safety of elotuzumab in combination with pomalidomide, carfilzomib, and low-dose dexamethasone for patients with high-risk relapsed/refractory (RR)MM (NCT03104270). Of 13 enrolled patients, 11 were evaluable for efficacy. Overall response rate and clinical benefit rate were 45.4% and 54.5%, respectively. Deep responses were observed including two complete responses. The novel quadruplet combination was overall well-tolerated, with clinically manageable adverse events. Common adverse events of ≥ grade 3 included lymphopenia (15%), anemia (15%), sepsis (15%), pneumonia (15%), and hypophosphatemia (15%). The novel combination showed promising efficacy and was well tolerated in this heavily pretreated MM population. Even though the study was terminated early prior to completion of enrollment, the results indicate that this may be a promising therapeutic approach for high-risk RRMM patients, which warrants further study.


Asunto(s)
Mieloma Múltiple , Anticuerpos Monoclonales Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Dexametasona , Humanos , Mieloma Múltiple/diagnóstico , Mieloma Múltiple/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/etiología , Oligopéptidos , Talidomida/análogos & derivados
11.
Eur J Haematol ; 107(3): 318-323, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-33993536

RESUMEN

Multiple myeloma (MM) patients with smoldering (S) disease are defined by a lack of CRAB/SLiM criteria but may transform into disease requiring treatment. The International Myeloma Working Group risk stratification model for SMM uses serum M-protein, serum-free light chain ratio, and bone marrow plasma cell percentage. We investigated whether baseline serum B-cell maturation antigen (sBCMA) levels are predictive of disease progression among 65 patients with SMM. A receiver operating characteristic curve was used to establish a definition for high-risk baseline sBCMA. Mantel Byar analysis was used to examine whether high-risk sBCMA was correlated with shorter time to transformation, and a time-dependent cox proportional hazard was used to determine whether it is independent of other risk factors. A z test for proportions was used to compare the percentage of patients that progressed among high-risk versus low-risk sBCMA patients. A baseline sBCMA level ≥137.5 mg/ml was found to be the optimal cutoff between high- and low-risk SMM patients. Patients with high-risk sBCMA levels had a shorter time to transformation (P = .000332). sBCMA was also higher at the time of transformation than baseline levels (P = .0116). sBCMA was the only variable found to be significantly predictive of time to transformation and additionally was found to be independent of other risk factors. In this study, we have shown for the first time that sBCMA levels predict transformation of SMM to active disease and that these levels increase at the time of transformation. These results are consistent with other studies showing that active MM patients undergoing therapy with higher baseline sBCMA levels are more likely to progress early and its levels increase at the time of disease progression.


Asunto(s)
Antígeno de Maduración de Linfocitos B/sangre , Biomarcadores de Tumor/sangre , Mieloma Múltiple Quiescente/sangre , Mieloma Múltiple Quiescente/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Antígeno de Maduración de Linfocitos B/inmunología , Biomarcadores de Tumor/inmunología , Progresión de la Enfermedad , Femenino , Glicoproteínas/sangre , Glicoproteínas/inmunología , Humanos , Cadenas kappa de Inmunoglobulina/sangre , Cadenas lambda de Inmunoglobulina/sangre , Masculino , Persona de Mediana Edad , Células Plasmáticas/inmunología , Células Plasmáticas/patología , Pronóstico , Modelos de Riesgos Proporcionales , Curva ROC , Factores de Riesgo , Mieloma Múltiple Quiescente/inmunología , Mieloma Múltiple Quiescente/mortalidad
12.
Ann Hematol ; 100(8): 2061-2070, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-33987683

RESUMEN

Venetoclax is a BCL-2 inhibitor currently indicated for use in treating hematologic malignancies with recommended doses ranging from 400 to 600 mg/day. Although currently not FDA-approved to treat multiple myeloma (MM) patients, there is a growing number of reports indicating its efficacy as a salvage therapy for these patients, especially for those with the t(11;14) chromosomal marker. These studies, however, have also indicated that venetoclax given at doses ≥ 400 mg/day can cause serious adverse events (SAEs) especially when administered with bortezomib, commonly related to infections. The purpose of this single-center retrospective study was to determine the efficacy of low dose venetoclax (defined as ≤ 250 mg/day) in combination with low dose bortezomib (defined as 1.0 mg/m2 per dose), daratumumab, and dexamethasone (Dvvd) as a salvage therapy for relapsed/refractory myeloma (RRMM) patients. Twenty-two RRMM patients were given venetoclax orally at doses ranging from 100 to 250 mg daily using this four-drug regimen. While the low doses resulted in reduced venetoclax efficacy among those lacking t(11;14) (overall response rate [ORR] = 31%), those harboring the t(11;14) marker exhibited an ORR of 80%. Notably, this response was without frequent infection-related SAEs as reported in previous studies. Together, the results of this study demonstrate that treatment of t(11;14) positive RRMM patients with Dvvd is both effective and well-tolerated.


Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Bortezomib/uso terapéutico , Compuestos Bicíclicos Heterocíclicos con Puentes/uso terapéutico , Dexametasona/uso terapéutico , Mieloma Múltiple/tratamiento farmacológico , Sulfonamidas/uso terapéutico , Anciano , Anticuerpos Monoclonales/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Bortezomib/administración & dosificación , Compuestos Bicíclicos Heterocíclicos con Puentes/administración & dosificación , Dexametasona/administración & dosificación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/tratamiento farmacológico , Estudios Retrospectivos , Sulfonamidas/administración & dosificación , Resultado del Tratamiento
13.
Ann Hematol ; 100(4): 1079-1085, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33237342

RESUMEN

The purpose of this single-center retrospective study was to determine the incidence of decreased blood phosphorus levels and hypophosphatemia among multiple myeloma (MM) patients treated with elotuzumab. Hypophosphatemia, which is defined as a serum phosphorus concentration < 2.5 mg/dL, leads to complications ranging from muscle weakness and disorientation to seizures and heart failure. A total of 23 MM patients receiving care in a clinic specializing in treatment of MM from July 2018 to March 2020 and treated with an elotuzumab-containing therapy were evaluated, and 9 were investigated for this study. Elotuzumab was given at 10 mg/kg weekly for the first two treatment cycles (28 days/cycle), followed by 10 mg/kg every other week for all subsequent cycles. Four different elotuzumab combination therapies were administered: 1) elotuzumab and dexamethasone 2) elotuzumab, lenalidomide and dexamethasone 3) elotuzumab, pomalidomide and dexamethasone and 4) elotuzumab, carfilzomib, pomalidomide, and dexamethasone. Phosphorous levels were determined at a median of every 13 days at intervals ranging from once weekly to once monthly until a phosphate supplement was prescribed to the patient or when elotuzumab treatment was discontinued. We found that regardless of elotuzumab combination therapy, all patients treated showed decreased phosphorus levels after initiating elotuzumab treatment with reductions ranging from 12.5% to 44.1% below baseline. Six participants (67%) demonstrated an average serum phosphorus at or below 2.5 mg/dL after starting elotuzumab therapy. This retrospective study suggests that hypophosphatemia commonly occurs among MM patients receiving elotuzumab-containing therapies.


Asunto(s)
Anticuerpos Monoclonales Humanizados/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Hipofosfatemia/inducido químicamente , Mieloma Múltiple/tratamiento farmacológico , Anciano , Anticuerpos Monoclonales Humanizados/administración & dosificación , Bortezomib/administración & dosificación , Dexametasona/administración & dosificación , Difosfonatos/administración & dosificación , Interacciones Farmacológicas , Femenino , Humanos , Hipofosfatemia/epidemiología , Lenalidomida/administración & dosificación , Masculino , Persona de Mediana Edad , Oligopéptidos/administración & dosificación , Estudios Retrospectivos , Talidomida/administración & dosificación , Talidomida/análogos & derivados
14.
Case Rep Oncol ; 13(3): 1103-1108, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33082755

RESUMEN

A 52-year-old African-American woman with a prior history of monoclonal gammopathy of undetermined significance (MGUS) developed infiltrating ductal carcinoma of the left breast. Following a mastectomy, she underwent reconstruction with a silicone gel breast implant. Three years later, her MGUS had progressed to active multiple myeloma (MM). She had a minimal response after two different regimens of bortezomib-based treatments and monthly zoledronic acid, and was placed on maintenance therapy with bortezomib, intravenous dexamethasone, and oral methylprednisolone, as well as ongoing monthly zoledronic acid. After 1 year of this maintenance therapy, during which her myeloma markers remained unchanged, she had her silicone implant replaced with saline. Despite no change in her myeloma treatment, her laboratory values began to steadily improve following removal of the silicone implant. Her M-protein decreased from 2.14 to 0.83 g/dL and her IgG levels from 3,330 to 1,210 mg/dL following replacement of her silicone implant with saline. To our knowledge, this is the first report in which removal of silicone implants improved the clinical status of a patient with MM following a year of maintenance therapy during which the patient's myeloma laboratory values remained unchanged. Further studies are warranted to determine if silicone breast implant removal can, in fact, improve MM patients' disease status.

17.
Clin Cancer Res ; 26(10): 2346-2353, 2020 05 15.
Artículo en Inglés | MEDLINE | ID: mdl-31937615

RESUMEN

PURPOSE: Ruxolitinib with lenalidomide and dexamethasone shows antimyeloma effects in vitro and in vivo. MUC1 leads to lenalidomide resistance in multiple myeloma cells, and ruxolitinib blocks its expression. Thus, ruxolitinib may restore sensitivity to lenalidomide. Therefore, a phase I trial was conducted to determine the safety and efficacy of ruxolitinib with lenalidomide and methylprednisolone for patients with relapsed/refractory multiple myeloma (RRMM) who had been treated with lenalidomide/steroids and a proteasome inhibitor and showed progressive disease at study entry. PATIENTS AND METHODS: A traditional 3+3 dose escalation design was used to enroll subjects in four cohorts with planned total enrollment of 28 patients. Subjects received ruxolitinib twice daily, lenalidomide daily on days 1-21 of a 28-day cycle, and methylprednisolone orally every other day. Primary endpoints were safety, clinical benefit rate (CBR), and overall response rate (ORR). RESULTS: Twenty-eight patients were enrolled. The median age was 67 years and received a median of six prior treatments including lenalidomide and steroids to which 93% were refractory. No dose-limiting toxicities occurred. The CBR and ORR were 46% and 38%, respectively. All 12 responding patients were refractory to lenalidomide. Grade 3 or grade 4 adverse events (AE) included anemia (18%), thrombocytopenia (14%), and lymphopenia (14%). Most common serious AEs included sepsis (11%) and pneumonia (11%). CONCLUSIONS: This phase I trial demonstrates that a JAK inhibitor, ruxolitinib, can overcome refractoriness to lenalidomide and steroids for patients with RRMM. These results represent a promising novel therapeutic approach for treating multiple myeloma (ClinicalTrials.gov number, NCT03110822).


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Mieloma Múltiple/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Dexametasona/administración & dosificación , Dexametasona/efectos adversos , Relación Dosis-Respuesta a Droga , Resistencia a Antineoplásicos , Femenino , Humanos , Janus Quinasa 1/antagonistas & inhibidores , Janus Quinasa 2/antagonistas & inhibidores , Lenalidomida/administración & dosificación , Lenalidomida/efectos adversos , Masculino , Persona de Mediana Edad , Mieloma Múltiple/metabolismo , Mieloma Múltiple/patología , Recurrencia Local de Neoplasia/metabolismo , Recurrencia Local de Neoplasia/patología , Nitrilos , Pirazoles/administración & dosificación , Pirazoles/efectos adversos , Pirimidinas , Tasa de Supervivencia
18.
Eur J Haematol ; 100(6): 621-623, 2018 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-29524348

RESUMEN

OBJECTIVE: To evaluate the efficacy and safety of elotuzumab and dexamethasone (Ed) for relapsed or refractory multiple myeloma (RRMM) patients. METHOD: This retrospective study evaluated the efficacy and safety of Ed treatment for 21 RRMM patients, 11 of whom were considered lenalidomide-refractory, and all of whom had progressed on at least 1 prior steroid-containing regimen. We also evaluated the efficacy of adding lenalidomide to a subset of patients following progression from Ed. RESULTS: The overall response rate (ORR) and clinical benefit rate (CBR) of Ed were 10% and 19%, respectively. An additional 52% of patients demonstrated stable disease as their best response. The median PFS was 1.8 months on Ed for all patients. Fifteen patients received ERd following progression on Ed, and 60% of these patients were lenalidomide-refractory. The ORR and CBR were 20% and 33%, respectively, and the median PFS was 3.4 months. CONCLUSION: Our results suggest that some patients can benefit from Ed without an accompanying immunomodulatory agent and that efficacy can be achieved with the addition of lenalidomide at the time of progression. No new safety signals were detected, except for thrombocytopenia in 1 patient on Ed.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/patología , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales Humanizados/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Dexametasona/administración & dosificación , Resistencia a Antineoplásicos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mieloma Múltiple/mortalidad , Recurrencia , Retratamiento , Estudios Retrospectivos , Resultado del Tratamiento
19.
Ann Hematol ; 96(3): 449-459, 2017 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-27933373

RESUMEN

New classes of drugs including the proteasome inhibitors (PI) bortezomib and, more recently, carfilzomib and the immunomodulatory agent lenalidomide have shown improved outcomes for multiple myeloma (MM) patients during the past decade. However, most of the studies reporting outcomes for patients receiving these drugs have relied on older data sets derived from large institutions that included patients not receiving their treatment at those facilities and represented only those eligible for clinical trials or were from sites where treatment options were limited. We have analyzed data from 258 MM patients who have received treatment with at least one of three agents: bortezomib, carfilzomib, and lenalidomide in a single clinic specializing in MM with respect to their responses and other outcomes to treatment regimens including these agents. Response rates were similar between these three drugs when used for the first time and again during subsequent treatment regimens. As expected, the clinical benefit rates (CBRs) were better for patients receiving their first treatment when compared to their use in subsequent treatment regimens. The CBRs were similar during their 2nd, 3rd, and 4th treatments containing these agents. Many patients refractory to these agents showed responses to regimens containing these same drugs when used in different combinations. In addition, patients refractory to one PI often responded to the other PI. The results of this study demonstrate that novel agents can be used repeatedly in novel combinations with significant clinical benefit for patients with MM.


Asunto(s)
Antineoplásicos/administración & dosificación , Bortezomib/administración & dosificación , Mieloma Múltiple/diagnóstico , Mieloma Múltiple/tratamiento farmacológico , Oligopéptidos/administración & dosificación , Talidomida/análogos & derivados , Adulto , Anciano , Anciano de 80 o más Años , Inhibidores de la Angiogénesis/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Estudios de Cohortes , Femenino , Humanos , Lenalidomida , Masculino , Persona de Mediana Edad , Mieloma Múltiple/mortalidad , Estudios Retrospectivos , Tasa de Supervivencia/tendencias , Talidomida/administración & dosificación , Resultado del Tratamiento
20.
Ann Hematol ; 96(3): 441-448, 2017 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-27913860

RESUMEN

Despite recent advances made in its treatment, multiple myeloma (MM) remains an incurable B cell malignancy. Thus, the objective for treating these patients is to prolong overall survival (OS) and preserve patients' quality of life. We have analyzed data from 264 consecutive MM patients who had their initial visit between July 1, 2004 and December 1, 2014 and have received treatment in a single clinic specializing in MM. We determined their progression-free survival (PFS, OS, and 5-year OS). The PFS for frontline (n = 165 treatments), salvage (n = 980), and all treatments (n = 1145) were 13.9, 4.6, and 5.5 months, respectively. The median OS of all patients was 98 months with a 5-year survival of 74%. The results of this study show a marked improvement in OS for unselected MM patients compared with historical data. There were no significant differences in OS between patients with different International Staging System (ISS) stages. Younger patients (<65 years old) showed a longer OS. The results of this study should help physicians predict outcomes for MM patients and be encouraging for patients with this B cell malignancy.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Mieloma Múltiple/diagnóstico , Mieloma Múltiple/tratamiento farmacológico , Servicio Ambulatorio en Hospital/tendencias , Adulto , Anciano , Anciano de 80 o más Años , Bortezomib/administración & dosificación , Femenino , Estudios de Seguimiento , Humanos , Lenalidomida , Masculino , Persona de Mediana Edad , Mieloma Múltiple/mortalidad , Oligopéptidos/administración & dosificación , Estudios Retrospectivos , Tasa de Supervivencia/tendencias , Talidomida/administración & dosificación , Talidomida/análogos & derivados
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