scholarly journals Aberrations Detected By FISH in Brazilian Multiple Myeloma Patients

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5509-5509
Author(s):  
Maria de Lourdes Chauffaille ◽  
Aline Dos Santos Borgo Perazzio
Keyword(s):  
Multiple Myeloma ◽  
High Risk ◽  
Plasma Cells ◽  
Conflicts Of Interest ◽  
High Risk Patients ◽  
Total Percentage ◽  
Genetic Abnormalities ◽  
Interphase Cells ◽  
Risk Patients ◽  
Standard Risk

Multiple myeloma (MM) is a heterogeneous plasma cell malignancy with genetic abnormalities that comprise the most important prognostic factors. Chromosomal aberrations also influence the evolution and treatment refractoriness. Abnormalities progress in a stepwise way, from the pre-malignant stage of monoclonal gammopathy of undetermined significance, through smoldering until symptomatic MM. While marrow karyotype reveals only <30% of aberrations, FISH may show in up 90% of cases. FISH has become an essential tool in diagnosis, risk-classification and personalized therapy. There are two main groups of abnormalities: primary (trisomies and 14q or IGH gene translocations) which occur in plasma cells evolving into clonal stage, and secondary (-13/13q-, del(17p), +1q21/del1p), occurring during disease progression. As there are few reports of genetic aberrations in Brazilian MM patients, the objective of this study was to enlarge the casuistic and compare results. Objective: To dissect FISH aberrations detected in a larger set of Brazilian MM patients. Material and Methods: From Jan 2012 to Nov 2017, 417 MM patients were selected for the study. FISH was performed on isolated CD138 immunomagnetic beads plasma cells, using probes for 6q23.3 (MYB), 11q12.1 (D11S3347), 11q22.3 (ATM), 13q14.3 (D13S319-D13S25-RB1), 13q34 (D13S1825-LAMP1), 14q32 (IGH, break-a-part), 17p13.1 (TP53) IGH/FGFR3, IGH/CCND1 and IGH/MAF, according to the manufacturer´s instructions. At least 100 interphase cells were counted, and results described according to ISCN 2016. The cut off level was in-house established by mean +2 standard deviation from normal bone marrow controls. Results: Patients mean and median ages were 63.9 and 64y, respectively. M:F rate was 1.5:1. FISH showed abnormalities in 80% (333) of cases. Considering primary abnormalities: IGH-FGFR3 rearrangements were detected in 22.5% (30 patients), IGH-CCND1 in 57.2% (76), IGH-MAF in 3.7% (5 patiens), and 16.6% (22) IGH-unidentified gene. The most frequent trisomies were: 6 (62 patients), 11 (93 patients) and 17 (33 patients), some co-occurring and others isolated. 89 (31.6%) cases presented >3 aberrations, from which 25% had del(17p) (TP53) as well; 65 cases had three aberrations and 127 less than three abnormalities. Referring to secondary aberrations, 67(20.1%) cases presented del(13q) (RB1 and LAMP) and 32 (9.6%) del(17p) (TP53). Stratifying to prognosis (mSmart 2.0) 37 (10%) patients were considered as high-risk; 92 (27.6%) intermediate; 160 (48%) standard and 44 were not classified. Discussion: Comparing these results to literature reports, at diagnosis, Brazilian MM patients have mean and medium ages younger than European and North American populations. This type of difference has been detected in other hematopoietic neoplasias as well. FISH results were thoroughly similar referring to the total percentage and type of aberrations, but some variations in the frequency of aberrations were observed. Most patients were classified in the standard-risk group, presenting hyperdiploidy (30%) and t(11;14)(19%). The percentage of high-risk patients was reasonable (10%). Most of those with more than three aberrations also presented del(17p), a marker of adverse cytogenetics, as expected. The frequency of del(17p) was not unexpected, most being heterozigous deletion. Cases described as IGH-unidentified gene rearrangements may have been due to the unavailability of probes for chromosomes 6 and 20, at the time of the study. The same happened to 1q gain and del(1p). In summary, the spectrum of aberrations detected allowed identifying high-risk patients, choosing adapted therapy and improving outcomes. Disclosures No relevant conflicts of interest to declare.

Risk Stratification and Targets in Multiple Myeloma: From Genomics to the Bedside

2018 ◽  
pp. 675-680 ◽  
Author(s):  
Aurore Perrot ◽  
Jill Corre ◽  
Hervé Avet-Loiseau
Keyword(s):  
Multiple Myeloma ◽  
High Risk ◽  
Plasma Cells ◽  
Mechanisms Of Action ◽  
The Past ◽  
Novel Drugs ◽  
Genetic Abnormalities ◽  
Frequent Mutations ◽  
Risk Patients ◽  
First Relapse

In the past 15 years, significant improvements in overall survival have been observed in multiple myeloma (MM), mainly due to the availability of novel drugs with variable mechanisms of action. However, these improvements do not benefit all patients, and some of them, defined as high risk, still display short survival. The most important risk factors are the genetic abnormalities present in the malignant plasma cells. The most important high-risk features are the del(17p), the del(1p32), the t(4;14), and 1q gains. Assessing these markers is mandatory at diagnosis and at least at first relapse, since it has been clearly shown that the lenalidomide-dexamethasone combination is not efficient in these high-risk patients. In contrast, a triplet combination adding a proteasome inhibitor or a monoclonal antibody to the lenalidomide-dexamethasone backbone clearly improves the survival. Another way to improve the outcome would be to specifically target genetic abnormalities with specific inhibitors. The sequencing of more than 1,000 MM exomes revealed again a huge heterogeneity. The most frequent mutations involve the KRAS and NRAS genes (20%–25% each). However, to date, no good RAS-inhibitors are clinically available, preventing targeted therapy. The only drugable target is the V600E BRAF mutation. Unfortunately, this specific mutation is present in only 3% of the patients. Finally, it has been recently reported a specific efficiency of the BCL2-inhibitor venetoclax in patients with the t(11;14) translocation, which is found in 20% of the patients.

Real-World Clinical Outcomes By Cytogenetic Risk Category in Relapsed or Refractory Multiple Myeloma: Evidence from a Cohort Review in France

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4784-4784
Author(s):  
Huamao Mark Lin ◽  
Keith L Davis ◽  
James A. Kaye ◽  
Katarina Luptakova ◽  
Lu Gao ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
High Risk ◽  
Partial Response ◽  
Research Funding ◽  
Complete Response ◽  
Line Treatment ◽  
Second Line ◽  
High Risk Patients ◽  
Risk Patients ◽  
Standard Risk

Abstract INTRODUCTION: Multiple Myeloma (MM) is an incurable hematologic cancer characterized by multiple recurrences. With each recurrence, patients have a lower probability of response and duration of response is shorter. Therefore, there is an unmet need to improve outcomes in relapsed/refractory multiple myeloma (RRMM). There is a shortage of data describing clinical features and outcomes in these patients in real-world practice, particularly with regard to differences in outcomes by baseline cytogenetic risk. To help address this information gap, this study analyzed data from a cohort of RRMM patients in France. METHODS: A retrospective observational review of medical records was conducted in a cohort of 200 patients with RRMM in France. Patients were selected (based on randomly generated first letter of last name) from the caseloads of 40 hematology/oncology providers across France practicing mainly in academic hospitals. Inclusion criteria were: ≥18 years of age at initial MM diagnosis; first determined to have RRMM between January 1, 2009 and December 31, 2011, where RRMM was defined by (1) first-line (induction) regimen of chemotherapy with or without stem cell transplant (SCT) and with or without other post-induction/SCT therapy and (2) disease progression while on or at any time after completion of first-line therapy. Patients could be alive or deceased at the time of record abstraction. Baseline cytogenetic risk was defined as follows: high-risk: cytogenetic abnormalities del(17p), t(4:14), or t(14;16); unknown/unassessed risk: patients for whom cytogenetics were unavailable; or standard-risk: all patients with known cytogenetics not classified as high-risk. Patients were assessed for treatment response, overall survival (OS) and progression-free survival (PFS) from date of first relapse (study index date). All analyses were descriptive. Survival was assessed using the Kaplan-Meier (K-M) method. RESULTS: Demographic and clinical characteristics of the study sample are presented in Table 1. A total of 55 high-risk and 113 standard-risk patients were identified; risk category was unknown or unassessed for 32 patients. Among all patients, mean (SD) age at RRMM diagnosis was 66.3 (8.9) years and 62% of the sample was male. Lenalidomide + dexamethasone was the most common second-line systemic regimen initiated (50% of high-risk patients, 59.5% of standard-risk patients receiving second-line treatment). A total of 114 patients (57%) initiated a third-line treatment. Despite clinical response in second-line treatment occurring sooner in high-risk patients (median: 106 days) than in standard-risk patients (median: 237 days), physician-assessed overall response rate (ORR) was lower in high-risk patients (63%: 17% complete response, 46% partial response) than standard-risk patients (91%: 26% complete response, 65% partial response) across all second-line treatments combined (Table 2).. For third-line treatment, ORR was lower in high-risk patients (54%: 12% complete response, 42% partial response) than standard-risk patients (74%: 9% complete response, 65% partial response). Among patients who initiated a second-line treatment (n = 192), 47.4% were deceased at the time of data collection. From second-line initiation, K-M estimates of 1- to 5-year OS and PFS were substantially lower for high-risk patients versus standard-risk. Specifically, the proportions of patients still alive 1, 3, and 5 years after second-line treatment initiation were 73%, 51%, and 36%, respectively, for high-risk patients and 94%, 73%, and 61% for standard-risk patients. The proportions of patients without disease progression at 1, 3, and 5 years after second-line initiation were 48%, 13.5%, and 5% for high-risk patients and 82%, 42%, and 14% for standard-risk patients. CONCLUSIONS: The importance of cytogenetic risk classification as a prognostic factor in RRMM was apparent in this retrospective review, in which patients with high-risk cytogenetics had less favorable outcomes in terms of ORR, OS, and PFS than standard-risk patients. Decreased response rate and lower PFS and OS was documented among patients with high-risk cytogenetics, which is in contrast to shorter time needed to achieve best clinical response in this subgroup. Results from this real-world study provide further confirmation of the unmet medical need presented by RRMM, especially for patients with high-risk cytogenetics. Disclosures Lin: Takeda: Employment. Davis:Takeda: Research Funding. Kaye:Takeda: Research Funding. Luptakova:Takeda Oncology: Employment. Gao:Takeda: Employment. Nagar:Takeda: Research Funding. Seal:Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Employment, Equity Ownership.

scholarly journals Is There an Unequal Benefit of Autologous Stem Cell Transplant in Different Cytogenetic Groups of High Risk Patients with Multiple Myeloma: The University of Miami Experience

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 42-43
Author(s):  
Fahmin Basher ◽  
Sandra Sanchez ◽  
Jonathan H. Schatz ◽  
James E. Hoffman ◽  
Lazaros J. Lekakis
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
High Risk ◽  
Retrospective Analysis ◽  
Comprehensive Cancer Center ◽  
High Risk Patients ◽  
Risk Patients ◽  
University Of Miami ◽  
The University ◽  
Standard Risk

BACKGROUND: Stratification using cytogenetics (CG), either metaphase karyotyping or fluorescence in situ hybridization (FISH) is used to identify patients (pts) with multiple myeloma (MM) who are at higher risk of relapse and tend to have poorer survival. It is largely unknown if autologous stem cell transplantation (auto-HCT) after high dose melphalan (200 mg/m2) is able to modify the survival of some of these high-risk MM pts and to make it comparable to standard risk. METHODS: Pts were classified as high risk (HR) if either conventional cytogenetics or FISH demonstrated at least one of the following 1q+, 1p-, 17p-, 13q-, t(4;14), or t(14;16), realizing that the inclusion of 13q- by FISH alone and 1p- in the HR MM definition is controversial. Pts with normal chromosomes or those with trisomies and hyperdiploidy were considered standard-risk (SR). We compared progression-free survival (PFS) and overall survival (OS) via a retrospective analysis of pts at the University of Miami Sylvester Comprehensive Cancer Center who underwent auto-HCT between January 2014 and December 2017 for MM. Survival analyses were performed using the log-rank test, with significance at p-value &lt; 0.05. RESULTS: Male pts comprised 56% of the population, and 40% of pts were of Hispanic ethnicity. Of 205 pts undergoing auto-HCT, 108 (53%) had at least one HR cytogenetic abnormality. Interestingly, the depth of response to pre-transplant induction was higher in pts classified as HR, with 71% (77 of 108) achieving at least a very good partial response (VGPR), while 24% (23 of 96) SR pts achieved VGPR. While OS remained largely unaffected in HR pts (34.0 m vs. 35.1 m, p = 0.27); HR pts had an inferior PFS compared to SR pts (21.9 m vs. 25.7 m, p = 0.041). The presence of trisomies did not negate the poorer PFS of HR pts. When we evaluated specific HR CG abnormalities, OS and PFS in patients with 1q+ or t(4;14) were surprisingly comparable to SR pts, indicating a significant benefit from auto-HCT. On the other hand, OS was significantly decreased in pts with 1p- when compared to standard risk (16.5 m vs. 35.1 m, p = 0.004) or other high-risk patients (16.5 m vs. 35.4 m, p = 0.01), implying that 1p- group derive no benefit from auto-HCT. Similarly, OS was shorter in pts with t(14;16) (16.5 m vs. 34.4 m, p = 0.025) and with 17p- (26.6 m vs. 35.1 m, p=0.01), however the PFS was not affected in these populations. In pts with 13q-, PFS was significantly shorter (20.3 m vs. 25.7 m, p=0.023) compared to SR pts without affecting OS. CONCLUSION: At our center in a retrospective analysis of 205 pts: a) patients with HR MM responded better and faster than SR pts to induction, b) those with 1p- did not derive any benefit from transplant and c) pts with 17p- and t(14;16) had some short term benefit (similar PFS to SR group) but at the end their OS remained inferior. Nevertheless, we consider a very important finding the fact that, by having auto-HCT, pts with 1q+ and t(4;14), equalized their PFS and OS to those of SR pts. Based on these findings, patients with 1q+ and t(4;14) should still have a transplant in CR1 even after optimal induction. Whether 17p- and t(14;16) pts can extend PFS benefit after transplant into OS benefit with maintenance regimens stronger than lenalidomide alone remains to be determined. Disclosures Hoffman: Celgene: Honoraria, Speakers Bureau; Loxo: Current equity holder in publicly-traded company; Seattle Genetics: Research Funding.

scholarly journals Trisomies in multiple myeloma: impact on survival in patients with high-risk cytogenetics

Blood ◽  
2012 ◽  
Vol 119 (9) ◽  
pp. 2100-2105 ◽  
Author(s):  
Shaji Kumar ◽  
Rafael Fonseca ◽  
Rhett P. Ketterling ◽  
Angela Dispenzieri ◽  
Martha Q. Lacy ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
High Risk ◽  
Median Overall Survival ◽  
Diagnostic Testing ◽  
Prognostic Significance ◽  
Genetic Abnormalities ◽  
Impact On Survival ◽  
Risk Patients ◽  
Standard Risk

Abstract Routine incorporation of FISH into multiple myeloma (MM) diagnostic testing has led to a better appreciation of the heterogeneity of genetic abnormalities associated with this disease. We studied a group of 484 patients with newly diagnosed symptomatic MM to better understand the prevalence of the various abnormalities and the prognostic significance of the overlapping abnormalities. A translocation involving the IgH locus and 1 of the 5 recurrent partner chromosomes was seen in 161 (33%) patients, and 275 (57%) had trisomy of at least 1 odd-numbered chromosome. High-risk FISH, defined as the presence of t(4;14), t(14;16), t(14;20), or loss of P53, was seen in 115 (24%) patients; the median overall survival for this group was 3.9 years, compared with “not reached” for standard-risk patients (P < .001). Among the patients with high-risk FISH, 49 patients who also had at least 1 trisomy had a median overall survival that was not reached, compared with 3 years for high-risk patients without a concurrent trisomy (P = .01). Based on the current findings, we conclude that the presence of trisomies in patients with t(4;14), t(14;16), t(14;20), or p53 deletion abnormalities in MM ameliorates the usual adverse impact associated with these prognostic markers.

Outcome according to cytogenetic abnormalities and DNA ploidy in myeloma patients receiving short induction with weekly bortezomib followed by maintenance

Blood ◽  
2011 ◽  
Vol 118 (17) ◽  
pp. 4547-4553 ◽  
Author(s):  
María-Victoria Mateos ◽  
Norma C. Gutiérrez ◽  
María-Luisa Martín-Ramos ◽  
Bruno Paiva ◽  
María-Angeles Montalbán ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
High Risk ◽  
Dna Ploidy ◽  
Progression Free Survival ◽  
Newly Diagnosed ◽  
Free Survival ◽  
Cytogenetic Abnormalities ◽  
High Risk Patients ◽  
Risk Patients ◽  
Standard Risk

Abstract Cytogenetic abnormalities (CAs) such as t(4;14), t(14;16) or del(17p), and nonhyperdiploidy are associated with poor prognosis in multiple myeloma. We evaluated the influence of CAs by FISH and DNA ploidy by flow cytometry on response and survival in 232 elderly, newly diagnosed multiple myeloma patients receiving an induction with weekly bortezomib followed by maintenance therapy with bortezomib-based combinations. Response was similar in the high-risk and standard-risk CA groups, both after induction (21% vs 27% complete responses [CRs]) and maintenance (39% vs 45% CR). However, high-risk patients showed shorter progression-free survival (PFS) than standard-risk patients, both from the first (24 vs 33 months; P = .04) and second randomization (17 vs 27 months; P = .01). This also translated into shorter overall survival (OS) for high-risk patients (3-year OS: 55% vs 77%; P = .001). This adverse prognosis applied to either t(4;14) or del(17p). Concerning DNA ploidy, hyperdiploid patients showed longer OS than nonhyperdiploid patients (77% vs 63% at 3 years; P = .04), and this was more evident in patients treated with bortezomib, thalidomide, and prednisone (77% vs 53% at 3 years; P = .02). The present schema does not overcome the negative prognosis of high-risk CAs and nonhyperdiploidy. This trial was registered with www.ClinicalTrials.gov as NCT00443235.

in Multiple Myeloma, High-Risk Features Are Modulated By Other Chromosomal changes : A Large Snparray IFM Study

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 641-641 ◽  
Author(s):  
Jill Corre ◽  
Benjamin Hebraud ◽  
Florence Magrangeas ◽  
Valérie Lauwers-Cances ◽  
Marie-Lorraine Chretien ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
High Risk ◽  
Structural Changes ◽  
Conflicts Of Interest ◽  
Snp Array ◽  
Derivative Chromosome ◽  
Chromosome 4 ◽  
High Risk Patients ◽  
Risk Patients ◽  
Chromosomal Changes

Abstract In multiple myeloma, cytogenetic changes display important value for patients’ outcome. In this setting, the most important changes are the del(17p), and the t(4;14), conferring a poor outcome. However, a certain heterogeneity is observed in survival of these high-risk patients. We hypothesized that other chromosomal changes may impact the outcome. We retrospectively analyzed a large series of 242 patients displaying either the t(4;14) (157 patients), or the del(17p) (110 patients), 25 patients presenting both abnormalities, using SNP-array. The main advantage of SNParray analyses is that all the unbalanced chromosomal changes are analyzed, in contrast to FISH which informs only for the chosed probes. For t(4;14), 144 patients have relapsed, and 103 have died. The median PFS was 1.4 year, and the median OS was 3.5 years. The median beta2-microglobulin (b2m) level was 4.0 mg/L (range, 1.2-38.3). The distribution of ISS stages 1, 2, and 3 was 35.4%, 26.4%, and 38.2%, respectively. Based on FISH results, 31.2% of the patients presented the abnormal configuration with only one fused signal. In all these patients, SNP-array analysis showed a loss of the telomeric part of one chromosome 4. In contrast to previous reports on this particularity in which the explanation was a loss of the derivative chromosome 14,17,18 we clearly show here that this configuration results from an unbalanced translocation. In patients with t(4;14), del(1p32) (p<0.001), del(16q) (p=0.03), del22q (p=0.04) and more than 30 chromosomal structural changes (p=0.02) negatively impacted PFS. For OS, del(13q14) (p=0.01), del(1p32) (p<0.001), and the number of chromosomal structural changes (p<0.05 and p=0.01 for [10;30[and more than 30 structural changes, respectively) worsened the prognosis of patients. In patients with del(17p) (110 patients), 99 patients relapsed, and 83 died. The median PFS was 1.3 year and the median OS was 2.7 years. The median beta2-microglobulin (b2m) level was 4.4 mg/L (range, 1.4-32.1). The distribution of ISS stages 1, 2, and 3 was 28.4%, 26.9%, and 44.8%, respectively. For patients with del(17p), del(1p32) (p<0.001), del(16q)] (p=0.03), del22q (p=0.04) and more than 30 chromosomal structural changes (p=0.02) negatively impacted PFS. For OS, del(1p32) (p=0.004) worsened the prognosis of patients, whereas more than 8 trisomies (p=0.008) was found to have a protective effect on survival. This study, which is the largest series of high-risk patients, analyzed with the most modern genomic technique, identified two main factors negatively impacting survival: del(1p32) and genomic complexity. Furthermore, we did show that 1/3 of patients with t(4;14) did not display upregulation of FGFR3 because of loss of the telomeric part of the chromosome 4. These patients do not present a better prognosis than those upregulating FGFR3, reinforcing the idea that FGFR3 activation is not important in the biology of the t(4;14). Disclosures No relevant conflicts of interest to declare.

scholarly journals Multiple Myeloma in the Time of COVID-19

2020 ◽  
Vol 143 (5) ◽  
pp. 410-416 ◽  
Author(s):  
Abdullah S. Al Saleh ◽  
Taimur Sher ◽  
Morie A. Gertz
Keyword(s):  
Multiple Myeloma ◽  
High Risk ◽  
Autologous Stem Cell Transplant ◽  
Cell Transplant ◽  
High Risk Patients ◽  
High Risk Disease ◽  
Risk Patients ◽  
Smoldering Myeloma ◽  
Standard Risk ◽  
High Risk Screening

We provide our recommendations (not evidence based) for managing multiple myeloma patients during the pandemic of COVID-19. We do not recommend therapy for smoldering myeloma patients (standard or high risk). Screening for COVID-19 should be done in all patients before therapy. For standard-risk patients, we recommend the following: ixazomib, lenalidomide, and dexamethasone (IRd) (preferred), cyclophosphamide lenalidomide and dexamethasone (CRd), daratumumab lenalidomide and dexamethasone (DRd), lenalidomide, bortezomib, and dexamethasone (RVd), or cyclophosphamide, bortezomib, and dexamethasone (CyBorD). For high-risk patients we recommend carfilzomib, lenalidomide, and dexamethasone (KRd) (preferred) or RVd. Decreasing the dose of dexamethasone to 20 mg and giving bortezomib subcutaneously once a week is recommended. We recommend delaying autologous stem cell transplant (ASCT), unless the patient has high-risk disease that is not responding well, or if the patient has plasma cell leukemia (PCL). Testing for COVID-19 should be done before ASCT. If a patient achieves a very good partial response or better, doses and frequency of drug administration can be modified. After 10–12 cycles, lenalidomide maintenance is recommended for standard-risk patients and bortezomib or ixazomib are recommended for high-risk patients. Daratumumab-based regimens are recommended for relapsed patients. Routine ASCT is not recommended for relapse during the epidemic unless the patient has an aggressive relapse or secondary PCL. Patients on current maintenance should continue their therapy.

scholarly journals LINC-28. EPIDEMIOLOGICAL CHARACTERISTICS AND SURVIVAL OUTCOMES OF CHILDREN WITH MEDULLOBLASTOMA TREATED AT THE NATIONAL CANCER INSTITUTE (INCA) IN RIO DE JANEIRO, BRAZIL

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii383-iii384
Author(s):  
Gabriela Oigman ◽  
Diana Osorio ◽  
Joseph Stanek ◽  
Jonathan Finlay ◽  
Denizar Vianna ◽  
...  
Keyword(s):  
High Risk ◽  
Maternal Education ◽  
Survival Outcomes ◽  
Middle Income ◽  
Female Ratio ◽  
High Risk Patients ◽  
Presenting Symptoms ◽  
Risk Patients ◽  
Epidemiological Characteristics ◽  
Standard Risk

Abstract BACKGROUND Medulloblastoma (MB), the most malignant brain tumor of childhood has survival outcomes exceeding 80% for standard risk and 60% for high risk patients in high-income countries (HIC). These results have not been replicated in low-to-middle income countries (LMIC), where 80% of children with cancer live. Brazil is an upper-middle income country according to World Bank, with features of LMIC and HIC. METHODS We conducted a retrospective review of 126 children (0–18 years) diagnosed with MB from 1997 to 2016 at INCA. Data on patients, disease characteristics and treatment information were retrieved from the charts and summarized descriptively; overall survival (OS) and event-free survival (EFS) were calculated using the Kaplan-Meier Method. RESULTS The male/female ratio was 1.42 and the median age at diagnosis was 7.9 years. Headache (79%) and nausea/vomiting (75%) were the most common presenting symptoms. The median time from onset of symptoms to surgery was 50 days. The OS for standard-risk patients was 69% and 53% for high-risk patients. Patients initiating radiation therapy within 42 days after surgery (70.6% versus 59.6% p=0.016) experienced better OS. Forty-five patients (35%) had metastatic disease at admission. Lower maternal education correlated with lower OS (71.3% versus 49% p=0.025). Patients who lived &gt;40km from INCA fared better (OS= 68.2% versus 51.1% p=0.032). Almost 20% of families lived below the Brazilian minimum wage. CONCLUSIONS These findings suggest that socioeconomic factors, education, early diagnosis and continuous data collection, besides oncological treatment must be adressed to improve the survival of children with MB.

scholarly journals The role of idecabtagene vicleucel in patients with heavily pretreated refractory multiple myeloma

2021 ◽  
Vol 12 ◽  
pp. 204062072110196
Author(s):  
Albert Oriol ◽  
Laura Abril ◽  
Anna Torrent ◽  
Gladys Ibarra ◽  
Josep-Maria Ribera
Keyword(s):  
Multiple Myeloma ◽  
High Risk ◽  
Safety Profile ◽  
Proteasome Inhibitors ◽  
Clinical Development ◽  
Phase Iii ◽  
Acceptable Safety Profile ◽  
Refractory Multiple Myeloma ◽  
High Risk Patients ◽  
Risk Patients

The development of several treatment options over the last 2 decades has led to a notable improvement in the survival of patients with multiple myeloma. Despite these advances, the disease remains incurable for most patients. Moreover, standard combinations of alkylating agents, immunomodulatory drugs, proteasome inhibitors, and monoclonal antibodies targeting CD38 and corticoids are exhausted relatively fast in a proportion of high-risk patients. Such high-risk patients account for over 20% of cases and currently represent a major unmet medical need. The challenge of drug resistance requires the development of highly active new agents with a radically different mechanism of action. Several immunotherapeutic modalities, including antibody–drug conjugates and T-cell engagers, appear to be promising choices for patients who develop resistance to standard combinations. Chimeric antigen-receptor-modified T cells (CAR-Ts) targeting B-cell maturation antigen have demonstrated encouraging efficacy and an acceptable safety profile compared with alternative options. Multiple CAR-Ts are in early stages of clinical development, but the first phase III trials with CAR-Ts are ongoing for two of them. After the recent publication of the results of a phase II trial confirming a notable efficacy and acceptable safety profile, idecabtagene vicleucel is the first CAR-T to gain regulatory US Food and Drug Administration approval to treat refractory multiple myeloma patients who have already been exposed to antibodies against CD38, proteasome inhibitors, and immunomodulatory agents and who are refractory to the last therapy. Here, we will discuss the preclinical and clinical development of idecabtagene vicleucel and its future role in the changing treatment landscape of relapsed and refractory multiple myeloma.

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