Effect of complete response pre- and post- autologous stem cell transplantation in multiple myeloma

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7604-7604
Author(s):  
F. Sayani ◽  
D. Stewart ◽  
L. Kmet ◽  
P. Faris ◽  
M. L. Savoie ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Complete Response ◽  
Therapeutic Agents ◽  
Line Treatment ◽  
Front Line ◽  
Response Status ◽  
The Impact ◽  
Novel Therapeutic

7604 Background: The value of achieving a complete response (CR) pre or post high dose therapy and autologous stem cell transplant (HDT-ASCT) in multiple myeloma is still uncertain. Knowing the impact of achieving a CR prior to HDT-ASCT on survival, may lead to the incorporation of novel therapeutic agents into the front line treatment of this disease. The aim of our study was to determine whether achieving a CR before or after HDT-ASCT affects overall survival (OS) in multiple myeloma patients. Methods: We performed a retrospective analysis of 88 consecutive myeloma patients receiving HDT-ASCT at our center from 1993 to 2004. The OS of patients achieving at least 90% reduction in their M-protein, i.e. complete response and very good partial response (CR/VGPR), pre or post HDT-ASCT, was compared to that of patients achieving a partial response or less (<90% reduction in M-protein). OS, defined as the number of months from HDT-ASCT to death or last follow up, was estimated by the Kaplan-Meier method. Response status was evaluated pre and at 100 days post HDT-ASCT. Results: Prior to HDT-ASCT, twenty-two (25%) patients achieved a CR/VGPR. Median follow-up time was 39 months for patients in CR/VGPR and 18 months for non-CR/VGPR group. OS at 5 years was 58% (95% CI: 21%-82%) for patients in CR/VGPR, compared to 69% (95% CI: 51%-81%) for all patients in PR or less prior to stem cell collection. Post HDT-ASCT, 48 (55%) patients achieved a CR/VGPR. Their OS estimate at 5 years was 67% (95% CI: 44%-82%) compared to 71% (95% CI: 27%-92%) for all other patients. Overall, 30% more patients achieved CR/VGPR post HDT-ASCT. However, the survival curves did not differ by response status pre or post HDT-ASCT (log-rank test p=0.58 and 0.57 respectively). Conclusions: Our results suggest that achieving a clinical CR/VGPR pre or post HDT-ASCT does not appear to impact OS. These results might have been influenced by the small sample size and the possible need for a longer follow-up time. A more robust definition of CR at the molecular level, plus the use of novel therapeutic agents in front-line treatment, may better define the impact of achieving CR in multiple myeloma. No significant financial relationships to disclose.

scholarly journals Bortezomib, doxorubicin and dexamethasone (PAD) front-line treatment of multiple myeloma: updated results after long-term follow-up

2008 ◽  
Vol 141 (4) ◽  
pp. 512-516 ◽  
Author(s):  
Rakesh Popat ◽  
Heather E. Oakervee ◽  
Simon Hallam ◽  
Nicola Curry ◽  
Liz Odeh ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Line Treatment ◽  
Front Line ◽  
Long Term Follow Up

Long Term Significance of Response in Multiple Myeloma After Stem Cell Transplantation.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1811-1811
Author(s):  
Joaquin Martínez-López ◽  
Joan Blade ◽  
M. Carmen Gomez del Castillo ◽  
Maria Victoria Mateos ◽  
Adrian Alegre ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Stem Cell ◽  
Partial Response ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Complete Response ◽  
Long Term Follow Up

Abstract Abstract 1811 Poster Board I-837 The prognostic significance of achieving complete remission (CR) in Multiple Myeloma (MM) has finally been accepted. However, available studies have been based on series with a median follow-up around 5 years. This time period is insufficient according to the current life expectation of MM. Aim To establish the real effect of prognosis of the different response categories in a cohort of MM patients treated with autologous stem cell transplantation (ASCT) after long term follow up. Patients and methods Follow-up from diagnosis of 344 MM patients transplanted between 1989 and 1998 has been updated. These patients were previously included in a study aimed at establishing the post-ASCT response significance in MM and to validate the EBMT classification (Br J Haemat 2000;109:438-46). It was possible to update the follow up of 322 patients as at April 2009. At this date 99 patients were alive with a median follow-up form diagnosis of 12.5 years. Response categories and evaluated cases were: i) Complete Response (IF-) (CR), n= 84 ii) near Complete Response (EF-/IF+) (nCR), n= 66 iii) Very good partial response (VGPR) (<90% reduction of M component), n= 66 iv) Partial response PR (reduction of M component between 90-50%), n= 113 v) Stable Disease (SD), n= 12, y vi) Progression (PD), n=14 Survival analyses were performed by Kaplan-Meier curves (log-rank test). Cox logistic regression was employed to establish variables associated with a higher survival. Results Significant differences in overall survival (OS) and event free survival (EFS) were found between CR and nCR groups (p 0.01 and 0.0022, respectively); or between CR and VGPR (p 0.0001 and 0.0035); no differences were detected between nRC and VGPR groups (p 0.21 and 0.99) and between these groups and PR group (p 0.1 y p 0.8). OS and EFS of patients with ED o PD were lower than the rest of the groups. Overall survival at 12 years was 43% in CR patients, 21% in nCR, 20% in VGPR, 30% in PR, 8% in SD and 0% in PD groups. Median survival (OS, EFS respectively) of each group was 91 months and 36 m, 26 m and 21 m, 20 m and 15 m, 31 m and 12 m, 8 m and 5 m, and 6 and 1 month. Land-mark study (10 years) found a plateau phase in OS and EFS after 11 years. Twenty two percent of patients are still alive with stable status between 11 and 15.54 years and only two cases had relapsed in the non CR group. In a regression study for OS, response was only one variable with statistical significance (CR P <0.0000, OR 0.044, IC-95%: 0.020-0.30). Conclusions In MM achieving CR after ASCT is the most important prognostic factor even after long-term follow-up. Relapse rate is very low in patients with >11 years of follow-up, this could mean a cure for patients in CR. Disclosures No relevant conflicts of interest to declare.

Impact of Deletion 17p On the Outcome of Autologous Hematopoietic Stem Cell Transplantation in Multiple Myeloma.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3099-3099
Author(s):  
Caitlin L. Costello ◽  
Edward D. Ball ◽  
Sue Corringham ◽  
Hongying Li ◽  
Karen Messer
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
High Risk ◽  
Complete Remission ◽  
Stem Cell Transplantation ◽  
Chromosomal Abnormalities ◽  
Treatment Plan ◽  
Normal Cytogenetics ◽  
The Impact

Abstract Abstract 3099 Background: The development of a risk-stratification model that relies on molecular cytogenetic markers to assess disease aggressiveness and provide therapeutic guidance would be beneficial for the management of patients with multiple myeloma (MM). High-risk cytogenetic abnormalities, including deletion 17p (del17p), are known to confer a poor prognosis. Intensified consolidation with high-dose therapy (HDT) and autologous stem cell transplantation (ASCT) following induction therapy has been proposed as the preferred initial treatment for high-risk MM, such as del17p. With this background, we report the impact of del17p on the timing and outcome of transplant in patients with MM. Methods: We performed a retrospective review of 226 patients with MM who underwent HDT/ASCT at the University of California, San Diego Moores Cancer Center between 1/2000 and 7/2011. Conventional cytogenetic analyses were utilized for all patients either at diagnosis or at relapse, but prior to ASCT. Fluorescence in situ hybridization was also assessed when available. The primary objective was to evaluate the impact of del17p, a known high-risk chromosomal abnormality, on the overall survival (OS) and progression-free survival (PFS) after ASCT, compared with patients without chromosomal abnormalities. A secondary objective was to assess the OS and PFS for patients with del17p who received ASCT within a year of diagnosis, compared with those who underwent ASCT more than 12 months from diagnosis. Results: In 226 patients with conventional cytogenetic data prior to ASCT, chromosomal abnormalities were noted in 82 (36%) patients. Of these, 21 (25%) patients harbored a del17p abnormality. Table 1 shows the patient characteristics and ASCT outcomes. Prior to undergoing ASCT, 4 (19%)patients with del17p achieved a complete remission (CR) or stringent complete remission (sCR), and 6 (29%) achieved a CR or sCR after ASCT. In patients without chromosomal abnormalities, 19 (13%) achieved CR or sCR prior to ASCT, and 45 (31%) achieved it after ASCT. Median follow-up of surviving patients was 47 months (range 5–283). Median PFS after ASCT in patients with del17p and normal cytogenetics were 8.3 months (95%CI: 4.6-N/A) and 33 months (95%CI: 21.7–61.8), respectively (HR 2.15, 95%CI: 1.19–3.89; p=0.011) (Figure 1). Median OS after ASCT in patients with del17p and normal cytogenetics were 47.5 months (95%CI: 19.9-N/A) and 68 months (95%CI 51.1-N/A), respectively (HR: 2.27, 95%CI 1.15–4.48; p=0.018) (Figure 2). Median PFS in patients with del17p who received an ASCT after 12 months and within 12 months from diagnosis was 6.13 months (95%CI: 2.7-NA) and 22.6 months (95%CI: 5.4-NA), respectively (HR=1.22, 95%CI 0.40–3.82; p=0.71). Median OS in del17p patients who received an ASCT after 12 months and within 12 months from diagnosis was 65.6 months (95%CI: 19.3-NA) and 47.5 months (95%CI: 19.9-NA), respectively (HR=0.97, 95%CI 0.26–3.62; p=0.96). Conclusions: In this single center study with long follow up, we demonstrate that a del17p abnormality in MM confers a shorter PFS and OS after ASCT. Furthermore, the use of HDT/ASCT as part of the upfront treatment plan within 12 months of diagnosis does not significantly affect the outcome in patients with a del17p abnormality. Further studies are required to better define a risk-stratified treatment plan for this subset of high-risk multiple myeloma. Disclosures: No relevant conflicts of interest to declare.

Pattern of Relapse and Progression After Autologous Stem-Cell Transplantation As Upfront Treatment for Multiple Myeloma

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3987-3987
Author(s):  
Carlos Fernández de Larrea ◽  
Raquel Jiménez ◽  
Laura Rosiñol ◽  
Eva Giné ◽  
Natalia Tovar ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Line Treatment ◽  
First Line ◽  
Asymptomatic Relapse ◽  
First Line Treatment

Abstract Abstract 3987 Background: Autologous stem cell transplantation (ASCT) is the gold standard as first-line treatment in young patients with multiple myeloma (MM). Prognostic factors have been usually related to patient characteristic and disease stage. Few investigations on the pattern of relapse or progression after ASCT have been addressed. The differentiation of serological or asymptomatic progression versus clinical relapse requiring treatment is also an important issue. The aim of this study was to investigate the characteristics at the time of relapse or progression in patients with MM who received ASCT as part of a first-line treatment. Patients and Methods: Two-hundred and eleven patients underwent melphalan-based ASCT at our institution during the last 18 years. Of these, 170 patients (87M/83F; median age 56 years, range 25 to 70) who achieved at the least a minimal response (PR) after no more of two induction lines before ASCT are the basis of this study. Initial baseline demographics, clinical and laboratory data at relapse or progression, and information concerning treatment and follow up were collected. The M-protein heavy-chain isotype was IgG (57%), IgA (23%), light chain only (14%) and others (3.5%). Only 2.5% were oligosecretory MM. Extramedullary plasmacytomas (EMP) were observed in 37 out of 170 patients (22%) at diagnosis. The ISS stage was I (45.3%), II (26.5%), III (18.8%) and unknown (9.5%). 12.6% of the patients had a serum creatinine level ≥2 mg/dL and 16.2% had hypercalcemia. The median follow-up for alive patients was 3.9 years (range 4 months to 18 years). Response, relapse, and progression were defined according to European Blood and Marrow Transplantation (EBMT) criteria. Results: Median PFS was 3.3 years (CI 95% 2.7 to 3.9 years) and the median OS of 6.8 years (CI 95% 3.9 to 9.6 years). 47.7% of the patients achieved a complete remission (CR). As of December 2011, 93 patients (54.7%) had relapsed or progressed after ASCT. 37 out of the 93 patients (40%) had relapsed from CR, while the remaining 60% had progressed from PR. A serological or asymptomatic relapse/progression was as frequent as a symptomatic one (49.5% vs. 50.5%, respectively), the latter requiring immediate treatment in the median of a month. Patients with serological relapse/progression had a significantly longer OS than those requiring immediate treatment (p=0.002)(Figure). The main clinical reasons to start myeloma therapy were anemia (43%), new bone lytic lesions (36%), EMP (23.7%), bone pain (14.4%), renal insufficiency (12.2%) and/or hypercalcemia (9%). 22 of the 93 patients (24%) relapsed/progressing patients had EMP at the time of progression. In three of them, the extramedullary involvement was the only criteria of progression. The presence of EMP at diagnosis was significantly associated with extramedullary disease at relapse (p=0.001). In fact, 12 out of the 22 patients (54.5%) with EMP at relapse had also EMP at the time of diagnosis. Median time between serological relapse or progression and treatment was of only 5.6 months (range 0 to 5.6 years). However, in 12 out of 46 patients (26%) with serological relapse/progression, treatment was not initiated within first two years. Finally, time to next treatment was significantly longer in patients relapsing from CR (median 2.85 years; CI 95% 2.1 to 3.6) vs. those progressing from PR (median 1.65 years; CI 95% 1.1 to 2.2) (p=0.017). Conclusion: After ASCT, serological or asymptomatic relapse/progression is observed in about one half of the patients. The treatment-free interval in these patients is longer in patients relapsing from CR than in those progressing from PR. Patients with symptomatic relapse/progression have shorter OS. Extramedullary involvement is frequent, being the highest risk in patients with EMP at diagnosis. Finally, relapse/progression with extramedullary disease only is rare. Disclosures: No relevant conflicts of interest to declare.

Sustained High Rates of Complete Response and Minimal Residual Disease Negativity after 8 Cycles of Carfilzomib (CFZ), Lenalidomide (LEN), and Dexamethasone (DEX) Followed By 2 Years of Lenalidomide Maintenance (CRd-R) in Patients with High-Risk Smoldering Multiple Myeloma: Updated Results of Clinical and Correlative Phase 2 Study

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3339-3339 ◽  
Author(s):  
Dickran Kazandjian ◽  
Neha S Korde ◽  
Mark Roschewski ◽  
Sham Mailankody ◽  
Candis Morrison ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Combination Therapy ◽  
Minimal Residual Disease ◽  
Research Funding ◽  
Residual Disease ◽  
Complete Response ◽  
Risk Of Progression ◽  
Minimal Residual

Abstract Background: High-risk smoldering multiple myeloma (HR-SMM) is a plasma cell dyscrasia which has a 5-year risk of progression to symptomatic multiple myeloma (MM) of approximately 75% based on current risk models. With the availability of novel therapies, early treatment may decrease the risk of progression and prolong survival as evidenced by the recent QuiRedex study results. More recently, studies have demonstrated that triplet regimens are superior to doublet in MM and whole exome sequencing in HR-SMM is indicative of treatment susceptible biology in early disease; supporting the use of effective combination therapy as early intervention. Expanding on our initial results using modern CRd-R therapy in HR-SMM patients (Korde et al. JAMA Onc 2015) we show unprecedented high rates of obtained and sustained complete response (CR) and minimal residual disease negativity (MRDneg CR) in an expanded cohort of patients with a median follow-up of ~3 years. Methods: Treatment-na•ve patients with HR-SMM (IMWG 2010 criteria; Mayo or PETHEMA models) were treated for 8 cycles (28-day cycles) with CFZ 20/36 mg/m2 IV days 1, 2, 8, 9, 15, 16; LEN 25 mg PO days 1-21, and DEX 20/10 mg IV/PO days 1, 2, 8, 9, 15, 16, 22, 23. Transplant eligible patients underwent stem cell collection after ≥4 cycles of CRd and then continued CRd treatment (i.e. by-default-delayed high-dose melphalan with autologous stem cell transplant; HDM-ASCT). After 8 cycles of combination therapy, patients with SD or better received 2 years of LEN 10 mg PO maintenance. The primary objective was best response (ORR), followed by secondary objectives of progression free survival (PFS) and response duration (DoR) which were assessed after every cycle of induction and every 90 days during maintenance. Correlative studies including assessment of minimal residual disease (MRD) by multi-color flow cytometry (bone marrow aspirate; 10-5 sensitivity) as defined by updated 2016 IMWG response criteria were performed after 8 cycles of induction and 1 and 2 years of maintenance LEN. Results: Eighteen patients meeting eligibility criteria were enrolled (data-lock 7/20/2016). Demographics and disease characteristics are shown in Table 1. Best ORR and >= VGPR rate (n=18) with CRd-R was 100% (Table 2). The proportion of patients who obtained stringent CR/CR after 8 cycles of induction, 1 year of maintenance and 2 years of maintenance was 61%, 89%, and 89%, respectively. Of evaluable patients who achieved at least a CR, the proportion of patients who obtained MRD negativity (MRDneg CR) at the same time-points was 91%, 71%, and 75%, respectively. DoR and PFS at 36 months was 94% and overall survival with a median follow-up duration of 31 months was 100%. Toxicities Grade 3-4 occurring in >1 patient included lymphopenia (39%), neutropenia (28%), anemia (22%), diarrhea (17%), lung infection (17%), hypophosphatemia (11%), and thromboembolic event (11%). Significant serious adverse events included CHF which occurred in one patient. Conclusions: Early treatment of HR-SMM with modern CRd-R combination therapy with by-default-delayed HDM-ASCT resulted in unprecedented high rates of CR and MRDneg CR after 8 cycles of CRd. Following 2 years of additional LEN maintenance therapy, the CR and sustained MRDneg CR rates were 89% and 69%, respectively. Given the significant risk of progression to symptomatic MM and associated life limiting end-organ damage, early intervention for patients with HR-SMM with effective triplet-based therapies may be warranted. This first proof-of-principle study has thus far demonstrated exceptional clinical benefit. Therefore, this study will be re-opened to enrollment and long-term follow up results collected to expand on these promising results. Updated results will be presented at the Annual Meeting. Disclosures Korde: Medscape: Honoraria. Bhutani:Prothena: Research Funding; Takeda Oncology: Research Funding, Speakers Bureau; Bristol-Myers Squibb: Speakers Bureau; Onyx, an Amgen subsidiary: Speakers Bureau. Landgren:BMS: Honoraria; Amgen: Honoraria, Research Funding; Novartis: Honoraria; Celgene: Honoraria, Research Funding; Takeda: Honoraria.

Long-term prognostic significance of response in multiple myeloma after stem cell transplantation

Blood ◽  
2011 ◽  
Vol 118 (3) ◽  
pp. 529-534 ◽  
Author(s):  
Joaquin Martinez-Lopez ◽  
Joan Blade ◽  
María-Victoria Mateos ◽  
Carlos Grande ◽  
Adrián Alegre ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Partial Response ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Prognostic Significance ◽  
Progression Free Survival ◽  
Complete Response

AbstractFor establishing the true effect of different response categories in patients with multiple myeloma (MM) treated with autologous stem cell transplantation, we evaluated, after a median follow-up of 153 months, 344 patients with MM who received a transplant between 1989 and 1998. Overall survival (OS) at 12 years was 35% in complete response (CR) patients, 22% in near complete response (nCR), 16% in very good partial response (VGPR), and 16% in partial response (PR) groups. Significant differences in OS and progression-free survival were found between CR and nCR groups (P = .01 and P = .002, respectively), between CR and VGPR groups (P = .0001 and P = .003), or between CR and PR groups (P = .003 and P = < 10−5); no differences were observed between the nCR and VGPR groups (P = .2 and P = .9) or between these groups and the PR group (P = .1 and P = .8). A landmark study found a plateau phase in OS after 11 years; 35% patients in the CR group and 11% in the nCR+VGPR+PR group are alive at 17 years; 2 cases had relapsed in the nCR+VGPR+PR group. In conclusion, MM achieving CR after autologous stem cell transplantation is a central prognostic factor. The relapse rate is low in patients with > 11 years of follow-up, possibly signifying a cure for patients in CR.

The Outcome of Different Types of Second-Line Therapy in Multiple Myeloma Patients Relapsing After Uniform Front-Line Treatment with High-Dose Melphalan and Autologous Stem Cell Transplantation.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2892-2892
Author(s):  
Claudia Crippa ◽  
Samantha Ferrari ◽  
Monica Drera ◽  
Marinella Calarco ◽  
Antonio Regazzoli ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
High Dose ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
Line Therapy ◽  
High Dose Melphalan

Abstract Abstract 2892 Poster Board II-868 Background and aim. While multiple myeloma (MM) still remains largely incurable, therapeutic options for patients with MM are expanding. However the best way to use the different effective regimens, either in combination or in sequence, during the course of MM in the single patient is still unknown. Data from controlled studies rarely report the treatments received before and after the enrollment of patients in the clinical trial, which may significantly impact on response and survival. As an example, the best treatment for patients relapsing after first-line high-dose melphalan (HD-Mel) and autologous stem cell transplantation (ASCT) is not standardized. To this end we have retrospectively analyzed an uniform cohort of such patients treated at our Institution, comparing their outcome according to the type of second-line and further consolidation treatment received. Patients and methods. In 156 patients affected by MM and treated between 1997 and 2008 with HD-Mel and ASCT as first line therapy, relapse has occurred in 92 (59%). Females were 39 (42%), males 53 (58%), median age was 60 (range 34-75). As induction therapy before ASCT, 89 (97%) had received VAD regimen, and only 3 (3%) thalidomide/bortezomib-based regimen. Sixty-one patients (66%) had received a single ASCT and 31 a double ASCT (34%). A second-line therapy was given to 87/92 patients. They were subdivided in 3 subgroups according to the type of second-line treatment received: 1) thalidomide-based regimens (THAL) were given to 55 pts (63%) followed by a consolidation ASCT in 13 (24%) 2) bortezomib-based regimens (BORT) were used in 13 (15%) and subsequent ASCT in 3 of them (23%) 3) chemotherapy and/or steroids (CHEMO) were used in 19 (22%) followed by ASCT in 15 (79%). Median follow-up from diagnosis was 57 (13-145) in THAL, 39 (17-140) in BORT and 59 months (25-113) in CHEMO respectively. The baseline characteristics, including age, of the three subgroups were similar as well as the CR/VGPR and ORR rates obtained after first-line treatment (THAL 47% and 87%; BORT 69% and 100%; CHEMO 53% and 100%, respectively). The subgroups also did not differ in median duration of first response, which ranged from 13 to 15 months and median time to second treatment, which was 26 months in all subgroups. The proportion of patients receiving a double ASCT were significantly higher in BORT (69%) compared to THAL (34%) (P=0.03) and CHEMO (5%) (p=0.002), and in THAL (34%) compared to CHEMO (5%) (p=0.015). Results. After second line therapy the ORR (CR+VGPR+ PR) of the three subgroups was: THAL 60%, BORT 77% and CHEMO 58%. (p=NS). The second CR/VGPR rate was non significantly higher after BORT (46%) than after THAL (25%) or CHEMO (21%) (p=0.17). Moreover, when considering patients not undergoing second-line consolidation ASCT, the ORR was significantly better in THAL and BORT subgroups compared to CHEMO (50%, 70% and 0%, respectively p=0.03). After a median follow-up from second-line treatment of 28 months (range 1-99), the 2-y PFS was 38% after THAL (median 18 months), 34% after BORT (median 16 months) and 17% after CHEMO (median 12 months) (p=NS). The 2-y OS was 78% (median 49 months), 70% (median not reached), and 70% (median 33 month) after THAL, BORT and CHEMO, respectively (p=NS). However when considering patients not undergoing second-line consolidation ASCT, the 2-y OS was significantly better after THAL and BORT than after CHEMO (p=0.024). Conclusion. In spite of having frequently received a first-line double ASCT, BORT patients seemed to achieve responses of better quality. However, in patients relapsing after first-line HD-Mel and ASCT, the choice of THAL, BORT or CHEMO-based regimens as second-line therapy did not seem to impact on overall response rates and survival, provided that patients treated with CHEMO could be consolidated with a second ASCT. Hence newer drugs may be reserved for those patients not fit for ASCT, preserving them for effective third-line treatment in the other patients. Disclosures: No relevant conflicts of interest to declare.

Very Good Partial Response and Complete Response Predict Superior Overall Survival and Progression Free Survival After Single Autologous Stem Cell Transplant in Patients with Multiple Myeloma,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4111-4111
Author(s):  
Victor H Jimenez-Zepeda ◽  
Donna E. Reece ◽  
Suzanne Trudel ◽  
Christine Chen ◽  
Andrew Winter ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Research Funding ◽  
Progression Free Survival ◽  
Complete Response ◽  
Autologous Stem Cell Transplant ◽  
Novel Agents ◽  
Cell Transplant ◽  
Free Survival ◽  
The Impact

Abstract Abstract 4111 In multiple myeloma (MM), the impact of complete response (CR) and very good partial response (VGPR) achievement has been shown mostly after introduction of high dose therapy (HDT) supported by autologous stem cell transplant (ASCT). Recently, the IFM group reported the impact of achievement of CR and VGPR in double ASCT. The purpose of this study is to confirm the prognostic value of CR/VGPR in a large group of patients treated with single ASCT. Methods All consecutive patients who underwent single ASCT at Princess Margaret Hospital between January 2000 and December 2007 were evaluated. Patients were mobilized with cyclophosphamide and G-CSF and majority were conditioned with melphalan 200mg/m2. Response to therapy was assessed according to the IMWC including VGPR. Progression Free Survival (PFS) and Overall Survival (OS) were measured from transplant date to the date of death or last follow-up. OS and DFS were analyzed using the Kaplan-Meier Method. The Cox proportional hazard model was used to assess CR and VGPR and some other prognostic markers at presentation such as age, B2Mg> 460 μmol/L, LDH> 350 IU/L, CRP> 20mg/L, albumin<35g/L and creatinine > 200 μmol/L. All p-values were 2-sided and statistically significant if <0.05. Results 788 patients were identified for the study; their median age was 56 years (30–73). Patient's characteristics are listed in Table 1. Response was assessed at day 100 after ASCT and showed a CR of 6%, PR of 37.5%, and VGPR of 53% (Overall Response rate of 95.5%). Median OS and PFS for the group were 77.43 months and 20.63 months respectively. The median OS and PFS were significantly better for patients who achieved CR/VGPR, 104.5 months versus 51.7 months, and 26.3 months versus 13.53 months respectively. With a median follow-up of 44 months there is no significant difference in OS for those patients who achieved VGPR/CR after induction therapy with novel agents. However, PFS is better in those patients receiving novel agents who achieved VGPR/CR (Median PFS of 24.63months versus 12.4 months respectively (p=0.01). Multivariate analysis shows CR/VGPR as an independent prognostic factor for OS and PFS (Fig 1 and 2). B2Mg> 460 μmol/L, LDH> 350 IU/L, CRP > 20mg/L, albumin<35g/L and creatinine > 200 μmol/L failed to be important factor for survival in the multivariate analysis. Our data suggests that VGPR/CR is clearly important in the pre-novel agents era and for the smaller group of patients who had novel agents induction there is a benefit in PFS and with a longer follow-up perhaps in OS. In conclusion, VGPR/CR remains a simple and powerful indicator in the context of single ASCT and should be considered a relevant objective for MM treatment. Table 1. Clinical characteristics of patients with Multiple Myeloma undergoing single ASCT Clinical characteristic N=788 Median Range % Age (years) 58 31–74 Male 59.4% Female 40.6% Hemoglobin (g/L) 114 54–180 Creatinine (μmol/L) 107 28–1409 B2-microglobulin ((μmol/L) (N=718) 508 260–7270 Albumin (g/L) (N=650) 38 23–54 IgG 51.1% IgA 31.3% IgM 0.4% IgD 0.7% Biclonal 9.9% Not Detected 6.6 Kappa 59.4% Lambda 32.9% Biclonal 2% Not Detected 5.7% Calcium (μmol/L) 2.29 1.62–4.66 LDH (IU/L) (N=754) 235 50–1470 Induction Treatment: 52.2% VAD 22.8% Dexamethasone 6.3% TD 2.3% CP 3.8% DPACE/DTPACE 1.7% DVD 8% CyBORD 2% VD Ab: VAD: Vincristine, Adriamycin and dexamethasone, TD: Thalidomide and Dexamethasone; CP: Cyclophosphamide and Prednisone, DVD: Doxil, Velcade and Dexamethasone, CyBORD: Cyclophosphamide, Bortezomib and Dexamethasone and VD: Valcade and Dexamethasone Disclosures: Jimenez-Zepeda: J & J: Honoraria. Reece:Bristol, Meyers, Squibb: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Johnson&Johnson: Research Funding; Merck: Honoraria, Research Funding; Otsuka: Honoraria, Research Funding; Millennium: Research Funding; Amgen: Honoraria. Chen:Celgene Corporation: Consultancy, Honoraria, Research Funding. Kukreti:Celgene: Honoraria.

Erstlinientherapie des behandlungsbedürftigen Multiplen Myeloms – Aktuelle Empfehlungen

2020 ◽  
Vol 145 (12) ◽  
pp. 813-819
Author(s):  
Lukas John ◽  
Hartmut Goldschmidt ◽  
Christof Scheid
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Stem Cell ◽  
Maintenance Therapy ◽  
High Dose Chemotherapy ◽  
Therapeutic Agents ◽  
High Dose ◽  
Current Standard ◽  
Effective Treatment Option ◽  
Novel Therapeutic

AbstractDue to the introduction of novel therapeutic agents, the prognosis of Multiple Myeloma has greatly improved over the last decades. The current standard for fit patients is a bortezomib-based induction therapy, followed by high-dose chemotherapy and autologous stem cell transplantation and lenalidomide-based maintenance therapy. For older, non-transplant-eligible patients, daratumumab in combination with bortezomib or lenalidomide offers a well-tolerated, effective treatment option. Despite large improvements, there is still no cure for most myeloma patients, the aim of therapy is therefore to reach a deep remission to prevent lasting damage followed by a continuous maintenance therapy to uphold the remission and prolong overall survival.

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