Up-Front Thalidomide-Dexamethasone (THAL) and Double Autologous Transplantation (Double TX) for Multiple Myeloma: Comparison with Double TX without Added Thalidomide and Prognostic Implications of Chromosome 13 Deletion and Translocation t(4;14).

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3081-3081 ◽  
Author(s):  
Michele Cavo ◽  
Nicoletta Testoni ◽  
Carolina Terragna ◽  
Elena Zamagni ◽  
Paola Tacchetti ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Autologous Transplantation ◽  
Lower Probability ◽  
Fish Analysis ◽  
Primary Therapy ◽  
Cytogenetic Abnormalities ◽  
Chromosome 13 ◽  
Prognostic Implications ◽  
Intent To Treat

Abstract Aim of the present sudy was to evaluate the benefit of novel agents combined with conventional therapies in multiple myeloma (MM), with particular emphasis on patients (pts) carrying adverse cytogenetic abnormalities. For this purpose, we analyzed a series of 142 pts who received thalidomide-dexamethasone (thal-dex) and double autologous transplantation (double Tx). By study design, thal-dex was administered from the outset until the second autologous Tx. On an intent-to-treat basis, stringently defined (immumofixation negative) complete remission (CR) rate following double Tx and thal-dex was 54%. This value was significantly higher (P=0.0009) compared to the 33% observed in a comparable series of 129 pts who received double Tx without thal-dex. In comparison with these latter patients, addition of thal-dex to double Tx significantly prolonged PFS (median: 31 vs 42 months; P=0.04) and did not adversely affect survival after post-transplant relapse (P=0.7). All 142 pts included in the study were investigated at baseline for the presence of chromosome 13 deletion [del(13)] by FISH analysis and of t(4;14) using a RT-PCR assay. An analysis on an intent-to-treat basis performed according to the presence or absence of these cytogenetic abnormalities revealed that the probability to respond (more than 90% reduction in M protein concentration) to primary therapy with thal-dex for 94 pts who carried both del(13) and t(4;14) was significantly lower compared to that of 69 pts with del(13) alone (12% vs 41%, respectively; P=0.012) and of 18 pts with t(4;14) alone (12% vs 50%, respectively; P=0.006). The lower probability of response to first-line thal-dex therapy conferred by the presence of both del(13) and t(4;14) was completely offset by subsequent application of double Tx and thal-dex. Indeed, on an intent-to-treat basis, the probability to attain a very good partial response or CR for pts with both del(13) and t(4;14) positivity was 68% compared to 80% for pts with both del(13) and t(4;14) negativity (P=0.1). With a median follow-up of 24 months, the 3-year projected probabilities of OS and PFS were 80% and 59%, respectively (intent-to-treat). The presence or absence of t(4;14) had no significant impact on the 3-year projected probability of OS (80.12% vs 80.42%, respectively; P=0.3). Furthermore, an analysis of pts who actually received thal-dex and double Tx showed that curves of OS and EFS were almost superimposable among pts who carried or lacked both del(13) and t(4;14). Indeed, the 3-year projected probability of OS for pts with both these cytogenetic abnormalities was 92% compared to 88% for pts who were negative for both del(13) and t(4;14); (P=0.7); the corresponding figures for EFS were 70% vs 77%, respectively (P=0.9). These results suggest that thal-dex combined with double Tx may overcome the unfavourable prognosis conferred by del(13) and t(4;14). A longer follow-up is required before definite conclusions can be drawn.

Continuous absence of metaphase-defined cytogenetic abnormalities, especially of chromosome 13 and hypodiploidy, ensures long-term survival in multiple myeloma treated with Total Therapy I: interpretation in the context of global gene expression

Blood ◽  
2003 ◽  
Vol 101 (10) ◽  
pp. 3849-3856 ◽  
Author(s):  
John Shaughnessy ◽  
Joth Jacobson ◽  
Jeff Sawyer ◽  
Jason McCoy ◽  
Athanasios Fassas ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Multiple Myeloma ◽  
Global Gene Expression ◽  
Cell Cycle Gene ◽  
Term Survival ◽  
Cytogenetic Abnormalities ◽  
Chromosome 13 ◽  
Prognostic Implications ◽  
Total Therapy

Abstract Metaphase cytogenetic abnormalities (CAs), especially of chromosome 13 (CA 13), confer a grave prognosis in multiple myeloma even with tandem autotransplantations as applied in Total Therapy I, which enrolled 231 patients between 1989 and 1994. With a median follow-up of almost 9 years, the prognostic implications of all individual CAs, detected prior to treatment and at relapse, were investigated. Among all CAs and standard prognostic factors examined prior to therapy, only hypodiploidy and CA 13 (hypo–13 CA), alone or in combination, were associated with shortest event-free survival and overall survival (OS). The shortest postrelapse OS was observed with hypo–13 CA, which was newly detected in 18 of all 28 patients presenting with this abnormality at relapse. Superior prognosis was associated with the absence of any CA at both diagnosis and relapse (10-year OS, 40%). The lack of independent prognostic implications of other CAs points to a uniquely aggressive behavior of hypo–13 CA (present in 16% of patients at diagnosis). With the use of microarray data in 146 patients enrolled in Total Therapy II, overexpression of cell cycle genes distinguished CA from no CA, especially in cases of del(13) detected by interphase fluorescence in situ hybridization (FISH). FISH 13, resulting in a haploinsufficiency of RB1 and other genes mapping to chromosome 13, as well as activation of IGF1R, appears to have an amplifying effect on cell cycle gene expression, thus providing a molecular explanation for the dire outcome of patients with CA 13 compared with those with other CAs.

scholarly journals Poor prognosis in multiple myeloma is associated only with partial or complete deletions of chromosome 13 or abnormalities involving 11q and not with other karyotype abnormalities

Blood ◽  
1995 ◽  
Vol 86 (11) ◽  
pp. 4250-4256 ◽  
Author(s):  
G Tricot ◽  
B Barlogie ◽  
S Jagannath ◽  
D Bracy ◽  
S Mattox ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Poor Prognosis ◽  
Chromosomal Abnormalities ◽  
Multivariate Regression Analysis ◽  
Significant Variable ◽  
Chromosome 13 ◽  
Reactive Protein ◽  
Dismal Prognosis ◽  
Prognostic Implications ◽  
Beta 2 Microglobulin

Chromosomal abnormalities have major biologic and prognostic implications in leukemias. Cytogenetic information in typically hypoproliferative multiple myeloma (MM) is limited because of difficulties in obtaining analyzable metaphases. In this study, karyotypes and other known prognostic factors were analyzed in 155 newly diagnosed MM patients, entered on an intensive treatment program with two autotransplants. Complete remission (CR), event-free (EFS) and overall survival (OS) were analyzed using standard statistical methods. Abnormal cytogenetics were found in 39% of patients and were associated with a significantly lower CR rate (27% v 48%; P = .008). EFS and OS were inferior in patients with either partial or complete deletion of chromosome 13 or 11q abnormalities (“unfavorable” karyotype) when compared with the remaining patients (P < .001) who, as a group, had a similar prognosis irrespective of cytogenetic findings, ie, inevaluable, normal, or abnormal but without an “unfavorable” karyotype. The patients with abnormalities of both chromosomes 11 and 13 had a dismal prognosis with median EFS and OS of only 11 and 12 months, respectively. Significant associations were noted between an “unfavorable” karyotype and IgA isotype, elevated levels of beta-2 microglobulin (B2M, > or = 3 mg/L) and age > 60 years. On multivariate regression analysis, the absence of an “unfavorable” karyotype was the most significant variable associated with prolonged EFS and OS (P = .0001 and .0002, respectively). Other independent favorable variables were age less than 60 years, C-reactive protein (CRP) < or = 0.4 mg/dL and bone marrow plasmacytosis < or = 50% before treatment. On a multivariate analysis without cytogenetics, these same three standard parameters were identified as the only favorable variables. Patients not having all three standard favorable variables had a significantly lower CR rate (P = .03), EFS (P = .0001), and OS (P = .002) if an unfavorable karyotype was detected. We conclude that, in this program of uniformly treated MM patients, a poor prognosis was associated predominantly with abnormalities of chromosomes 11 and 13.

scholarly journals Daratumumab plus lenalidomide and dexamethasone in relapsed/refractory multiple myeloma: extended follow-up of POLLUX, a randomized, open-label, phase 3 study

Leukemia ◽  
2020 ◽  
Vol 34 (7) ◽  
pp. 1875-1884 ◽  
Author(s):  
Nizar J. Bahlis ◽  
Meletios A. Dimopoulos ◽  
Darrell J. White ◽  
Lotfi Benboubker ◽  
Gordon Cook ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Residual Disease ◽  
Progression Free Survival ◽  
Complete Response ◽  
Open Label ◽  
Refractory Multiple Myeloma ◽  
Open Label Phase ◽  
Intent To Treat ◽  
Line Of Therapy

Abstract In POLLUX, daratumumab (D) plus lenalidomide/dexamethasone (Rd) reduced the risk of disease progression or death by 63% and increased the overall response rate (ORR) versus Rd in relapsed/refractory multiple myeloma (RRMM). Updated efficacy and safety after >3 years of follow-up are presented. Patients (N = 569) with ≥1 prior line received Rd (lenalidomide, 25 mg, on Days 1–21 of each 28-day cycle; dexamethasone, 40 mg, weekly) ± daratumumab at the approved dosing schedule. Minimal residual disease (MRD) was assessed by next-generation sequencing. After 44.3 months median follow-up, D-Rd prolonged progression-free survival (PFS) in the intent-to-treat population (median 44.5 vs 17.5 months; HR, 0.44; 95% CI, 0.35–0.55; P < 0.0001) and in patient subgroups. D-Rd demonstrated higher ORR (92.9 vs 76.4%; P < 0.0001) and deeper responses, including complete response or better (56.6 vs 23.2%; P < 0.0001) and MRD negativity (10–5; 30.4 vs 5.3%; P < 0.0001). Median time to next therapy was prolonged with D-Rd (50.6 vs 23.1 months; HR, 0.39; 95% CI, 0.31–0.50; P < 0.0001). Median PFS on subsequent line of therapy (PFS2) was not reached with D-Rd versus 31.7 months with Rd (HR, 0.53; 95% CI, 0.42–0.68; P < 0.0001). No new safety concerns were reported. These data support using D-Rd in patients with RRMM after first relapse.

scholarly journals High incidence of chromosome 13 deletion in multiple myeloma detected by multiprobe interphase FISH

Blood ◽  
2000 ◽  
Vol 96 (4) ◽  
pp. 1505-1511 ◽  
Author(s):  
John Shaughnessy ◽  
Erming Tian ◽  
Jeffrey Sawyer ◽  
Klaus Bumm ◽  
Reid Landes ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Poor Prognosis ◽  
Plasma Cells ◽  
Suppressor Gene ◽  
Homozygous Deletion ◽  
Cell Labeling ◽  
Fish Analysis ◽  
Chromosome 13 ◽  
High Incidence ◽  
Homozygous Deletions

Abstract Multiple myeloma (MM) is a hypoproliferative malignancy yielding informative karyotypes in no more than 30% of newly diagnosed cases. Although cytogenetic and molecular deletion of chromosome 13 is associated with poor prognosis, a MM tumor suppressor gene (TSG) has not been identified. To localize a minimal deleted region of chromosome 13, clonotypic plasma cells from 50 consecutive patients with MM were subjected to interphase fluorescence in situ hybridization (FISH) analysis using a panel of 11 probes spanning the entire long arm of chromosome 13. Whereas chromosome 13 abnormalities were absent in plasma cells from 25 normal donors, 86% of patients with MM demonstrated such aberrations. Heterogeneity, both in deletion frequency and extent, was confirmed by simultaneous FISH with 2 chromosome 13 probes. Deletion hot spots were noted at D13S272 (70%) and D13S31 (64%), 2 unlinked loci at 13q14. Homozygous deletions at these loci occurred in 12% (simultaneously in 8%) of the cases. Molecular deletions were found in all 14 patients with morphologic deletions, in 21 of 24 with uninformative karyotypes, and 8 of 12 patients with karyotype abnormalities lacking chromosome 13 deletion. Homozygous deletion of any marker was noted in 4% with low and in 36% with higher plasma cell labeling index greater than 0.4% (P = .01). The absence of increasing deletion incidence and extent with therapy duration suggests that the observed lesions are not induced by treatment. The high incidence and extent of chromosome 13 deletions require the correlation of specific deletion(s) with poor prognosis. These analyses will provide valuable guidance toward cloning of an MM-TSG.

Frequency of Clonal Evolution by FISH in Untreated, Early Stage Patients with CLL: A Prospective, Longitudinal Study with Long Clinical Follow-Up.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2098-2098 ◽  
Author(s):  
Tait D. Shanafelt ◽  
Stephanie Fink ◽  
Tom E. Witzig ◽  
Sarah F. Paternoster ◽  
Stephanie Smoley ◽  
...  
Keyword(s):  
Overall Survival ◽  
Median Time ◽  
Early Stage ◽  
Clonal Evolution ◽  
Normal Karyotype ◽  
Risk Category ◽  
Fish Analysis ◽  
Cytogenetic Abnormalities ◽  
Study Participants

Abstract Background: Using fluorescent in-situ hybridization (FISH), a number of investigators have identified specific cytogenetic abnormalities that identify CLL patients with a more aggressive (17p-, 11q-) or indolent (13q-) disease course. Some have suggested patients who initially have a normal karyotype may acquire new chromosome abnormalities during the course of their disease. Since patients with specific cytogenetic abnormalities (17p-, 11q-) are less likely to respond to purine nucleoside analogues, such clonal evolution has potential implications for treatment as well as prognosis. No study has prospectively investigated the frequency of clonal evolution in a cohort of patients with newly diagnosed untreated CLL. Methods: Between 1994 and 2000, we enrolled 167 patients with previously untreated CLL seen at Mayo Clinic in a prospective trial evaluating the prognostic importance of cytogenetic abnormalities and clonal evolution detected by FISH. All patients provided a baseline blood specimen for FISH testing and follow-up specimens over the following 24 months. Other research samples from later timepoints were tested where available. Study participants were contacted by mail in 2004 to update vital and treatment status. Of 83 living responders, 70 (84%) indicated they would be willing to provide an additional follow-up sample for cytogenetic analysis of whom 48 have returned a sample to date. Results of clinical FISH testing during the follow-up interval were also abstracted. FISH was performed on interphase nuclei from blood as we have previously described (BJH 121:287). Results: Median age at diagnosis was 64. Median time from diagnosis to study enrollment was 3.3 months. 94% of patients had early stage disease at enrollment (88 Rai 0; 48 Rai I, 18 Rai II, 2 Rai III; 8 Rai IV). Median follow-up time from diagnosis for all 164 eligible study participants was 8.5 years (range: 0.33–22.9 yrs). As of last follow-up, 48% of patients have received treatment and 57 (35%) have died. 75% of patients had chromosome abnormalities on FISH testing at baseline. The frequency of individual cytogenetic abnormalities on baseline FISH analysis along with overall survival by hierarchical FISH risk category are shown in Table I. 106 patients had sequential samples for FISH analysis at least 2 years apart, 61 had samples at least 5 years apart, and 22 had samples at least 10 years apart. 15 patients had evidence of clonal evolution during follow up as evidenced by a new FISH anomaly not present on the baseline specimen. No clonal evolution was observed in the first 2 years of follow-up (n=106), however of 61 patients with samples at least 5 years apart, 14 (23%) had evidence of clonal evolution. Median time for development of a new cytogenetic abnormality among these patients was 9.3 years. Conclusions: Clonal evolution occurs during the course of disease for approximately 25% of patients with early stage CLL. Clonal evolution appears to occur at low frequency during the first 2 years of follow-up but increases in frequency after 5 years. This finding has potentially significant implications for prognosis and treatment of patients with CLL. FISH Risk Category* N (Baseline) Median Overall Survival (Years) * Difference between groups significant p=0.0038 13q- x 1 37 14.4 13q- x2 35 17 Normal Karyotype 40 13.2 12+ 24 11.1 11q- 12 8.6 17p- 10 10.5 6q- 2 4.1 Other 2 Not reached

CKS1B Over-Expression Significantly Predicts for a Lower Rate of Response to Primary Therapy with Thalidomide-Dexamethasone (Thali-Dex) for Newly Diagnosed Multiple Myeloma (MM) Patients.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 371-371
Author(s):  
Matteo Renzulli ◽  
C. Terragna ◽  
N. Testoni ◽  
E. Montanari ◽  
P. Tosi ◽  
...  
Keyword(s):  
Response To Therapy ◽  
Remission Induction ◽  
Lower Probability ◽  
High Dose ◽  
Fish Analysis ◽  
Primary Therapy ◽  
Newly Diagnosed ◽  
Rt Pcr ◽  
Over Expression ◽  
The Relationship

Abstract In MM tandem duplication and jumping translocations of the q21 band of chromosome (chr.) 1 are acquired during progression of the disease and can lead to chr.1q amplification. In several studies, chr. 1 amplification has been linked to poor prognosis after both conventional and high-dose chemotherapy. Recently, a subset of genes mapping on 1q21 band has been identified, whose increased expression may be due to increased DNA copy number. Among these genes, CKS1B has been one of the most significantly upregulated. CKS1B regulates SCF skp2 mediated ubiquitination and proteolysis of the cyclin dependent kinase inhibitor p27Kip1, whose low expression has been reported to be an independent adverse prognostic factor in MM patients. Aim of the present study was to investigate the relationship between CKS1B expression and response to primary therapy with thali-dex in a large series of patients with newly diagnosed MM. Secondary endpoint was to explore the relationship between CKS1B expression and del(13), as assessed by FISH analysis, and t(4;14), as evaluated by an RT-PCR assay designed to detect the presence of IgH/MMSET fusion gene. A total of 132 patients were analyzed. The presence of t(4;14) and CKS1B expression were investigated in all patients, while del(13) was studied in 129/132 patients. CKS1B expression was evaluated by Real-time RT-PCR. CKS1B values were separated in four different quartiles, with expression levels increasing progressively from quartile 1 to 4. Response to therapy was evaluated according to the criteria proposed by Bladè et al. The Fisher test and the Mann-Whitney test were applied for statistical analysis. On an intent-to-treat basis, the overall probability to respond (≥ partial response, PR) to up-front thali-dex therapy was 71%, while 38 patients (29%) either did not respond (NR) or progressed. Median CKS1B expression value was significantly higher in NR in comparison with patients who attained at least a PR: 1.42 (range 0.15–52.35) vs. 0.89 (range 0–11.88), respectively (p=0.01). In particular, the proportion of NR patients in the CKS1B expression quartile 4 was significantly higher as opposed to the frequency of NR in the CKS1B expression quartiles 1 to 3 (45.5% vs. 23.2%, respectively; p= 0.02). CKS1B over expression did not correlate with the presence of t(4;14) or del(13). Only 6 patients harbouring t(4;14) fell into the CKS1B expression quartile 4, as opposed to 32 patients included into the CKS1B expression quartiles 1–3 (18.2% vs. 32.3%; p, not significant). Similarly, the frequency of del(13) was comparable in the CKS1B expression quartile 4 and in the CKS1B expression quartiles 1–3 (34.4% vs. 44.3%; p, not significant). Likewise, only 2 patients carrying both t(4;14) and del(13) fell into the CKS1B expression quartile 4, as opposed to 15 patients who fell into the CKS1B expression quartiles 1–3 (6.5% vs. 15.3%; p, not significant). In conclusion, in patients with newly diagnosed MM, CKS1B over expression at baseline predicts for a significantly lower probability of response to primary remission induction therapy with thali-dex. Poor response to thali-dex conferred by CKS1B over expression is independent from the presence of t(4;14) and/or del(13). Supported by Università di Bologna, Progetti di Ricerca ex-60% (M.C.); Ministero dell’Università e Ricerca Scientifica (MIUR), progetto FIRB, RBAU012E9A_001 (M.C.); and Fondazione Carisbo.

An Update of a Comparison of Nonmyeloablative Allografting with Autografting for Newly Diagnosed Myeloma.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 482-482
Author(s):  
B. Bruno ◽  
R. Sorasio ◽  
F. Patriarca ◽  
N. Mordini ◽  
B. Allione ◽  
...  
Keyword(s):  
Statistical Power ◽  
Autologous Transplantation ◽  
New Drugs ◽  
High Dose ◽  
Newly Diagnosed ◽  
Cox Models ◽  
Intention To Treat ◽  
Hematological Cancers ◽  
Intent To Treat

Abstract The concept of genetic randomisation has been applied to assess clinical outcomes between patients with hematological cancers treated with allografting or other therapies. Though not universally accepted, the comparison by the intention-to-treat principle between patients with HLA-identical siblings, who can be assigned to allografting, and those without, who cannot receive an allograft, is used as a surrogate for an unbiased randomisation. We previously published the results of a study where the treatment assignment of 162 newly diagnosed patients younger than 65 years was based only on the presence/absence of an HLA-identical sibling (Bruno et al, N Engl J Med). First-line treatment plans included a cytoreductive autograft followed by a nonmyeloablative allograft (Tandem auto-allo) or a second melphalan-based autograft (Double-auto). Primary endpoints were overall (OS) and event-free (EFS) survivals by intention-to-treat analysis. The 80 patients with a sibling donor were offered a Tandem auto-allo and the 82 without a Double-auto after high (140–200 mg/m2) or intermediate dose melphalan (100 mg/m2). After a median follow up of 45 (range 21–90) months, OS and EFS were significantly longer in patients with donors: 80 versus 54 months (p=0.01) and 35 versus 29 months (p=0.02). Median OS was not reached in the 58 (out of 60 enrolled, 97%) patients who completed Tandem auto-allo and was 58 months in the 46 (out of 59 enrolled, 78%) who completed high-dose double-auto (p=0.03). Here, we report a update analysis. At a median follow up of 56 months, OS was not reached for the 80 patients with an HLA-identical sibling and was 56 months for those without (HR 0.53, CI 95% 0.33–0.86, p=0.009). EFS remained significantly longer in patients with HLA-identical siblings: 35 versus 29 months (HR: 0.61; 95% Cl: 0.42–0.88, p=0.008). Median OS was not reached in the 58 patients who completed Tandem auto-allo and was 63 months in the 46 who completed high-dose double-auto (HR 0.47, CI 95% 0.25–0.86, p=0.016). EFS was 43 and 33 months (HR 0.64, CI 95% 0.40–1.02, p=0.06). By multivariate analysis, the presence of HLA-identical siblings was significantly correlated with longer OS and EFS. We carried out a stratified analysis, on the intent-to-treat population, that defined a patient subgroup at high risk in the light of high b -2-microglobulin levels or presence of del(13). The adjusted HRs by Cox models were 0.34 for OS and 0.52 for EFS similar to those obtained in the whole series. Though this exploratory analysis has low statistical power, its results indicate that del(13) does not offset the advantage in OS and EFS for patients with an HLA-identical sibling, but do not exclude an impact of del(13) in those patients undergoing an allograft. Attal et al. (N Engl J Med) previously reported median OS and EFS of 58 and 30 months, respectively, after double autologous transplantation, consistent with our results (OS: 63 months; EFS: 33 months). However, the EFS after Tandem auto-allo also indicates that long-term disease control is an issue. Allografting and new drugs with molecular targets should not be viewed as mutually exclusive. Thus, it is imperative to thoroughly explore their roles in increasing the response rates and their duration in Tandem auto-allo.

Autologous Hematopoietic Stem Cell Transplantation in Multiple Myeloma for Long-Term Follow-up: Single Center Results

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5836-5836
Author(s):  
Weiwei Sui ◽  
Dehui Zou ◽  
Gang An ◽  
Shuhui Deng ◽  
Yan Xu ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Autologous Transplantation ◽  
First Line ◽  
Hematopoietic Stem ◽  
Agent Based ◽  
Total Treatment ◽  
Long Term Follow Up ◽  
Baseline Characteristics

Abstract Objective: To evaluate the efficacy and long-term outcome of the total treatment of induction therapy, ASCT and consolidation and maintenance therapy. Methods: A retrospective analysis was made on in multiple myeloma patients in our center between April 1, 2003 and February 1, 2016. The 157 patietns received autologous hematopoietic stem cell transplantation and review the autologous transplantation of long-term follow-up results. Analysis of the effect of transplantation efficacy, the impact on survival remission of different transplantation depth, transplantation in first line or not, salvage transplantation, prognosis of different staging system and other factors. Results: The baseline characteristics of the patients were shown in table 1. Overall patient ASCT before total effective rate (ORR) was 93.6%, in which the complete remission (CR) ratio was 33.1%. After ASCT, the best treatment response rate of PR was 80.3%, and the rate of CR was 58.6%. 91.69 months of median follow-up, patients with an overall survival (OS) and progression free survival (PFS) respectively 91.69 and 50.76 months; in 2005 before the median OS and PFS 39.0m and 23.0m. In 2005 after respectively and 56.41m 120.90m, P = 0.000. The median OS and PFS in the first line transplantation group and salvage transplantation group were vs 54.21m 39.0m and vs 7.09m 119.0m (P value was 0). 136 cases of patients with R-ISS stage, I, II, III of the patients with the median survival time were 120.90m (n=46), 86.43m (n=69), 35.65m (n=21), there were significant differences between groups, p=0.000. Each period of PFS were 72.11m, 51.84m, 28.09m, I and II, III,, p=0.001 and p=0.03, while there was no significant difference between II and III, p=0.122. The received autologous transplantation as first-line and salvage treatment of patients with subgroup survival analysis, median OS of the R-ISS stage III patients and different 15.84m 35.65m, P = 0.031; two groups of patients the median PFS (phase I: 91.69m vs18.92m; II: vs 16.69m 53.42m; phase III: vs 5.91m 28.52m) have difference (P = 0.000). In the first-line transplantation group, transplantation is more than or equal to PR and did not get effective PR group between OS were significantly different; before transplantation achieved CR, PR but did not obtain Cr and did not get effective PR group between PFS were significantly different; after transplantation and achieved CR CR did not get the patients had a median PFS were 65.57m 48.13m, P = 0.039 and median OS no difference. Accept any kind of noval agent- based chemotherapy were significantly longer OS and PFS than traditional chemotherapy (P = 0.001, P = 0.004) .There was no obvious difference on median OS between based regimen (bortezomib group median OS: NR; thalidomide group:120.90m); PFS in thalidomide group (median PFS : NR vs 54.21m) significantly prolonged (P = 0.010). By comparing the baseline characteristics of the two groups, it was found that the PFS was significantly shorter in the bortezomib group with an extra medullary lesion. Multivariate analysis showed that only R-ISS and the depth of remission before transplantation had effect on OS (p=0.003) and PFS (p=0.036) respectively. Conclusion: The total treatment of novel agent-based chemotherapy and ASCT for transplantation-eligible multiple myeloma patients is effective, further improve the remission rate and remission depth, prolong PFS and OS, the overall median survival up to 120.9m. First line transplantation can significantly prolong the OS and PFS compared with salvage transplantation. R-ISS and pre-transplant remission depth are prognostic factors influencing survival of patients. The total treatment to thalidomide based without extramedullary perhaps makes patients get long-term survival. Disclosures No relevant conflicts of interest to declare.

FISH Analysis in Multiple Myeloma - a Retrospective Study from India

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5646-5646 ◽  
Author(s):  
Pratibha Dhiman ◽  
Shalini Goel ◽  
Priyanka Samal ◽  
Nitin Sood ◽  
Ritesh Sachdev ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
High Risk ◽  
Chromosomal Aberrations ◽  
Overall Response Rate ◽  
Response Rate ◽  
Indian Subcontinent ◽  
Fish Analysis ◽  
Interphase Fish

Abstract Introduction Multiple myeloma (MM) is a malignancy involving terminally differentiated plasma cells. It is characterized by a complex pattern of extensive genomic aberrations involving many chromosomes and it constitutes about 1% of all malignancies. Its exact incidence in India is not known. Based on data available from 6 population-based cancer registries in India (covering 0.3% of the population) its incidence varies from 0.3 to 1.9 per 100 000 for men and 0.4 to 1.3 per 100 000 for women. Among various prognostic markers in MM, cytogenetic abnormality detected by conventional cytogenetic and FISH studies are major factors deciding clinical outcome. Interphase FISH studies from various parts of the world have reported variable incidence (40 - 66%) of cytogenetic abberations. However, there is insufficient published data from Indian subcontinent addressing the frequency of chromosomal aberrations using interphase FISH in MM patients. Patients and Methods Sixty eight patients clinically diagnosed with multiple myeloma were studied. The retrospective period of recruitment was from Jan 2015 to June 2016. The diagnosis of MM was based on serum electrophoresis and immunofixation, bone marrow plasmacytosis, and end organ involvement. Interphase FISH analysis was performed on bone marrow samples using specific DNA probes- Del 13q14.3 (LSI D13S25) , t (4;14) ( Kreatech IgH/ FGFR3 DC-DF), t (11;14) (Zytovision directly labeled IgH/CCND1 DC-DF), t (14;16) (Kreatech IgH/ MAF DC-DF), Del 17p13.1( LSI TP53). A total of two hundred nuclei were enumerated for each FISH Panel probe and cut off for detection of deletion/ fusion signal in normal individuals was taken as 3%. An interim analysis of treatment protocols was also done. Results A total of 68 cases with MM were evaluated which included 55 males and 13 females. We report a median age of 58 years (37-86 years). Interphase FISH analysis was done in all patients. Out of sixty eight patients, 23 (33.82%) patients had one genetic abnormality. Results revealed that deletion 13q14.3 was the most frequent aberration. Out of 68 patients, 10 patients have 13q14 (14.7%) abnormality. This includes 70% males and 30% females. In addition absence of p53 at 17p13 was detected in 8/68 (11.8%) patients. Similarly 11q13 abnormality was observed in 3/68 (4.4%). IgH (14q32) aberrations were noted in 2/68 (2.94%) patients. Of which t(4;14) was detected in these patients, whereas none of them showed t(14;16). More than one chromosomal aberrations were present in 4 patients. Data for serum β2-microglobulin at the time of presentation could be evaluated in 52 patients only. Most of the patients 40(76.9%) belonged to ISS stage 3. From the available data, 4 patients with ISS stage 3 had high risk chromosomal abnormality whereas 3 patients with ISS stage 2 and none of the patient of ISS stage I disease had high risk chromosomal abnormality. A total of 40 patients received cyclophosphamide, bortezomib and dexamethasone as the primary treatment whereas 23 patients received Bortezomib, lenalidomide and dexamethasone based therapy. Post 2 cycles of cyclophosphamide based therapy showed an overall response rate (CR + VGPR) of 87.5% whereas in case of lenalidomide based therapy the overall response rate was 91%. Thirteen patients underwent autograft after durable response, out of which one had a clinical relapse within 3 months. Median survival can only be commented on further follow up. Conclusion In comparison to the west, the frequency of chromosomal aberrations are different and much less in India whereas the studies of median survival is comparable. An early age of presentation in Indian subcontinent is another issue to be addressed as we know that secondary mutations accumulate with increasing age, but a younger population presenting with same severity of disease needs exploration of additional abnormalities in India. Being a resource constraint country and non availability of molecular lab at every place, evaluation of each patient is difficult, however increasing awareness of the role of biology in the management of MM is inspiring the clinicians for detailed evaluation and close follow up of these patients. Certainly, larger trials are required to understand the biology of this disease in the country. Disclosures No relevant conflicts of interest to declare.

The Shreveport Myeloma Experience: Survival, Risk Factors and Other Malignancies in the Age of Stem Cell Transplantation

2015 ◽  
Vol 135 (3) ◽  
pp. 146-155 ◽  
Author(s):  
Reinhold Munker ◽  
Runhua Shi ◽  
Binu Nair ◽  
Srinivas Devarakonda ◽  
James D. Cotelingam ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Autologous Transplantation ◽  
Malignant Neoplasms ◽  
New Agents ◽  
Secondary Cancers ◽  
Academic Center ◽  
Seer Data ◽  
Second Malignant Neoplasms ◽  
Survival Risk

Background: The overall prognosis of multiple myeloma has improved significantly over the last 15 years. We wondered whether the overall improvement would also be seen in unselected patients in an academic center in Northwest Louisiana with a high proportion of minority patients, and if second malignant neoplasms are relevant for our patients. Materials and Methods: Between 1998 and 2009, 215 patients were treated for multiple myeloma at our center and had complete follow-up until May 2013. Results: The mean survival of patients with multiple myeloma increased from 3.25 to 5.34 years, which is comparable to patients treated at larger centers. No prognostic difference was observed in the subgroups of myeloma patients. Among 215 patients followed for the development of secondary cancers, 16 already had a preexisting or concomitant malignancy (7.4%) and 10 developed secondary cancers. Our data indicate a significant background of histologically unrelated cancers and a cumulative incidence of new cancers of about 20% after 10 years of follow-up. Based on SEER data, preexisting or secondary cancers were not statistically increased in our population. Conclusions: The use of autologous transplantation and the introduction of new agents resulted in a significant improvement in the prognosis of multiple myeloma. Other cancers are not statistically increased before or after multiple myeloma is diagnosed and are not prognostically relevant.

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