Reply. Kastritis E. et al. Reversibility of renal failure in newly diagnosed multiple myeloma patients treated with high dose dexamethasone containing regimes and the impact of novel agents. Haematologica 2007; 92:546 9

Abstract Introduction: Approximately 20% of patients with multiple myeloma present with renal failure (RF). It has been reported that with supportive measures and with antimyeloma treatment RF is reversible in 25 to 58% of patients. However, the impact of specific antimyeloma therapies on RF reversibility has not been clarified. Because high dose dexamethasone containing regimens are associated with a rapid myeloma control we performed a study to assess the impact of such regimens on RF reversibility. Patients and methods: Over the last decade 41 patients with RF, defined as a serum creatinine ≥2 mg/dL at the time of diagnosis, received primary treatment with high dose dexamethasone-based regimens in our Department. All patients were eligible fore assessment of reversibility of RF which was defined as a sustained decrease of serum creatinine to <1.5 mg/dl. Patients were separated into two groups. Group A: 26 patients who received VAD, VAD like regimens, Melphalan-high dose Dexamethasone or high-dose Dexamethasone alone and Group B: 15 patients who received high-dose Dexamethasone with thalidomide, with bortezomib or both. Results: Patients characteristics included: median age of 65 years, creatinine ≥4 mg/dL in 44%, Bence-Jones proteinuria ≥2 gr/day in 34%, ISS stage III in 76%, light chain only myeloma in 37%. Dialysis was required at presentation in 24% of patients. Response to treatment (EBMT criteria) was documented in 46% of patients of Group A and in 64% of patients of group B. The toxicity profile of novel agents-Dexamethasone combinations was similar to that seen in patients without RF. RF was reversed in 73% of all patients, in 69% of patients in group A and in 80% of patients in group B. After treatment only two patients initially requiring dialysis remained on renal replacement therapy. Multiple variables were assessed for their impact in RF reversibility: serum Creatinine ≥4 mg/dL and Bence-Jones proteinuria≥2 gr/day were associated with significantly lower probability of RF reversal (56% and 54% respectively). RF reversibility rate was 85% in patients who responded to treatment versus 56% in those who did not respond (p=0.046). The median time to RF reversal was 1.9 months for all patients, 2 months for patients of group A and 0.8 months for patients of group B (p=0.005). Conclusions: RF can be reversed in the majority of patients with newly diagnosed MM when they are treated with high-dose dexamethasone based regimens. Furthermore, normalization of serum creatinine occurs in one half of patients who do not meet criteria for objective response. Novel agents such as thalidomide and bortezomib or both can be safely combined with high dose dexamethasone for the treatment of Myeloma patients who present with RF and are associated with rapid rate of RF reversal.

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Efficacy of Modified Vrd-Lite for Transplant Ineligible Multiple Myeloma

Blood ◽

10.1182/blood-2020-143459 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 4-4

Author(s):

Mizuki Ogura ◽

Tadao Ishida ◽

Moe Nomura ◽

Hirofumi Irita ◽

Junichiro Nashimoto ◽

...

Keyword(s):

Adverse Effect ◽

Multiple Myeloma ◽

Cardiac Amyloidosis ◽

Staging System ◽

Treatment Interruption ◽

Cardiac Complications ◽

High Dose ◽

Al Amyloidosis ◽

Newly Diagnosed ◽

The Impact

BACKGROUND: High dose chemotherapy followed by autologous peripheral blood stem cell transplantation is an effective treatment for multiple myeloma. However, many patients with newly diagnosed multiple myeloma are transplant-ineligible because of their age and complications, result in a poorer prognosis than transplant-eligible patients. Furthermore, many of them cannot complete normal chemotherapy because of low tolerability. Here, we investigated the efficacy and safety of modified bortezomib with lenalidomide and dexamethasone (mVRD-lite) for transplant-ineligible patients with newly diagnosed multiple myeloma. STUDY DESIGN: A retrospective observational analysis was performed on patients who received mVRd-lite for the first line chemotherapy between Jan. 2016 and Mar. 2020 in our hospital. Patients who received high dose dexamethasone to reduce tumor burden, and patients who received bortezomib with dexamethasone or lenalidomide with dexamethasone as a reduction regimen of mVRd-lite were also included. We evaluated ORR, OS, PFS and adverse effect. mVRD-lite at first was administered over a 28-day cycle. Bortezomib 1.3 mg/m2 weekly was administered subcutaneously on days 1, 8, 15 and 22. Lenalidomide 15 mg was given orally 18 days, omitted on days 1, 8, 15, which are the days of bortezomib administration. Dexamethasone 20 mg was given orally on days 1, 2, 8, 9, 15, 16, 22, which are the day of and day after bortezomib. We also reviewed patients background, especially complication of light-chain amyloidosis and considered the impact of cardiac amyloidosis on patient prognosis. This study was conducted with the permission of the Ethics Review Board in our hospital. RESULTS: The subjects analyzed totaled 40 transplant-ineligible patients. 11(27.5%) patients were AL amyloidosis associated with multiple myeloma and 8(20%) patients had cardiac amyloidosis. Median age at diagnosis was 73 (range 48-86) and Male:Female=1:1. Most of them were judged inadequate to transplantation due to their age, general condition, or complication. One patient was ruled unfit to transplantation, because of his refusion. The Revised International Staging System (R-ISS) were I in 5 (12.5%), II in 25 (62.5%) and III in 8 (20%). 5(25%) patients switched to maintenance therapy. 17(42.5%) patients discontinued treatment, because of adverse effect (cardiac failure 4 ; two of them combined with cardiac amyloidosis, rash 4, peripheral neuropathy 3, infection 3, etc). 2(5%) patients died during treatment by mVRd-lite, because of Grade 4 adverse effect, such as pneumonia. 11(27.5%) patients died during observation period and causes of death were primary disease and TRM. 1(2.5%) patient was died of heart failure associated with cardiac amyloidosis. The overall response rate(ORR) during treatment period of mVRd-lite was obtained in 34(85%), including sCR in 5 (12.5%), VGPR in 13 (32.5%) and PR in 14(30%). 2(5%) patients achieved MRD negative. SD were observed in 3(7.5%) patients. 3(7.5%) patients were not evaluated efficacy because of treatment interruption by adverse effect. Overall survival rate at two year is 64.3%, median OS was not reached, at a median follow-up of 20 months. CONCLUSIONS: Transplant-ineligible multiple myeloma patients are associated with poor prognosis. Modified RVD-lite is one of the appropriate therapeutic options, in the transplant-ineligible multiple myeloma patients. Twenty-five percent of patients with cardiac amyloidosis had treatment discontinued due to cardiac complications. Further study is needed for treatment of patients with multiple myeloma complicated with cardiac amyloidosis. Disclosures Ishida: Janssen: Speakers Bureau; Celgene: Speakers Bureau; Ono pharmaceutical co: Speakers Bureau; Takeda pharmaceutical co: Speakers Bureau. Nashimoto:Janssen: Speakers Bureau; Celgene: Speakers Bureau. Tsukada:Takeda pharmaceutical co: Speakers Bureau. Suzuki:Takeda, Amgen, Janssen and Celgene: Consultancy; Takeda, Celgene, ONO, Amgen, Novartis, Sanofi, Bristol-Myers Squibb, AbbVie and Janssen: Honoraria; Bristol-Myers Squibb, Celgene and Amgen: Research Funding.

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Sequential High-Dose Dexamethasone and Response Adapted PAD (Bortezomib, Adriamycin, Dexamethasone) or VAD (Vincristine, Adriamycin, Dexamethasone) Induction Chemotherapy Followed by High-Dose Chemotherapy with Autologous Stem Cell Transplantation for Newly Diagnosed Multiple Myeloma; Open-Labelled, Multicenter Phase 2 Study (KMM-94 Study)-Interim Analysis

Blood ◽

10.1182/blood.v118.21.2044.2044 ◽

2011 ◽

Vol 118 (21) ◽

pp. 2044-2044

Author(s):

Jin Seok Kim ◽

Cheolwon Suh ◽

June-Won Cheong ◽

Kihyun Kim ◽

Yang Soo Kim ◽

...

Keyword(s):

Multiple Myeloma ◽

Stem Cell ◽

Stem Cell Transplantation ◽

Autologous Stem Cell Transplantation ◽

Induction Chemotherapy ◽

Induction Treatment ◽

High Dose ◽

Newly Diagnosed ◽

Younger Patients ◽

High Dose Dexamethasone

Abstract Abstract 2044 Background: Induction treatment followed by autologous stem cell transplantation (ASCT) is the standard therapy for the newly diagnosed younger patients with multiple myeloma (MM). Although new drugs such as lenalidomide or bortezomib have been shown the promising results as induction treatment, many different type of induction treatment regimens still have been used. We evaluate the efficacy and safety of the short course of high dose dexamethasone (HD dexa) and the response adapted PAD (Bortezomib, Adriamycin, Dexamethasone) or VAD (Vincristine, Adriamycin, Dexamethasone) induction chemotherapy in the newly diagnosed younger patients with MM. Methods: 107 newly diagnosed patients with MM from 21 institutions received 2nd cycles of HD dexa followed by PAD or VAD chemotherapy according to the response to the initial high dose dexamethasone. The primary endpoint was complete response (CR) + near CR rate after ASCT. Among 107 patents enrolled this study from November 2009, 25 patients (23%) have been dropped out. This trial will be continued until total 210 patients will be enrolled. The trial is registered on National Cancer Institute website, number NCT01255514. Results: One hundred seven patients (58 male, 49 female) were enrolled (median age; 56). 26 (24%) light chain disease were included. 31 (29%) patients were D-S stage II and 67 (63%) were stage III. According to the ISS, 23 (22%) patients had stage I, 51 (48%) had stage II and 33 (31%) had stage III. 26 (24%) patients had abnormal cytogenetics. There were 31% del13, 7% del17, 19% t(4;14), 15% t(14;16) and 28% t(11;14) in FISH analysis. Among the 82 evaluable patients, CR + PR rate was 48% (39/82) after 2nd cycles of HD dexa therapy. 39 patients (48%) received subsequent VAD chemotherapy and 43 patients (52%) received PAD chemotherapy. Among the 64 patients finished VAD or PAD chemotherapy, CR + PR rate was 83% (79%, 26/33 in VAD group vs. 87%, 27/31 in PAD group). 56 patients were finished ASCT until now. CR + near CR rate after ASCT were 61% (58% in VAD group vs 63% in PAD group). Mortality rate of this trial was 13% (11/82). The cause of death was disease progression (n=3), bleeding (n=1) and infections (n=7). Among 82 patients in whom VAD or PAD chemotherapy was actually performed, 1 year overall survival (OS) rate was 84.7%. 1 year survival rate was 93.8% versus 77.2% (P=0.049) with VAD versus PAD (median follow-up; 9.1 months). Conclusion: Risk adapted approach using initial steroid response showed good response results after ASCT compared with previous trial (CR + near CR rate of IFM 2005-01trial-Bortezomib+dexa induction & ASCT was 35%, J Clin Oncol. 2010;28:4621–9) The MM patients who had poor response to HD dexa also showed similar good response rate after ASCT compared with the patients who had good response to HD dexa treatment in this trial. PAD re-induction therapy after failure of initial steroid induction treatment might overcome the inferior results in the high risk MM patients. Therefore, initial steroid response adapted strategy might be the more cost-effective approach in the newly diagnosed ASCT eligible MM patients. Disclosures: No relevant conflicts of interest to declare.

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High-risk myeloma: a gene expression–based risk-stratification model for newly diagnosed multiple myeloma treated with high-dose therapy is predictive of outcome in relapsed disease treated with single-agent bortezomib or high-dose dexamethasone

Blood ◽

10.1182/blood-2007-10-119321 ◽

2008 ◽

Vol 111 (2) ◽

pp. 968-969 ◽

Cited By ~ 47

Author(s):

Fenghuang Zhan ◽

Bart Barlogie ◽

George Mulligan ◽

John D. Shaughnessy ◽

Barb Bryant

Keyword(s):

Gene Expression ◽

Multiple Myeloma ◽

High Risk ◽

Single Agent ◽

High Dose ◽

Newly Diagnosed ◽

High Dose Therapy ◽

High Dose Dexamethasone ◽

Risk Stratification Model ◽

Relapsed Disease

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Outcomes of Newly Diagnosed Myeloma Patients Requiring Dialysis: Dialysis Independence Is Associated with Rapid Myeloma Response and Predicts for Longer Survival

Blood ◽

10.1182/blood.v128.22.4492.4492 ◽

2016 ◽

Vol 128 (22) ◽

pp. 4492-4492

Author(s):

Meletios A. Dimopoulos ◽

Maria Roussou ◽

Maria Gavriatopoulou ◽

Despina Fotiou ◽

Dimitrios Ziogas ◽

...

Keyword(s):

Renal Failure ◽

High Risk ◽

Supportive Care ◽

Board Of Directors ◽

Light Chain ◽

Research Funding ◽

High Dose ◽

Newly Diagnosed ◽

Advisory Committees ◽

High Dose Dexamethasone

Abstract Renal failure (RF) is a common severe complication of symptomatic myeloma and may be severe enough to require extrarenal dialysis in approximately 1-5% of newly diagnosed patients. Severe RF is associated with high risk of early death and increased morbidity. Immediate effective anti-myeloma therapy and vigorous supportive care are the cornerstones of management. The use of high cutoff hemodialysis to rapidly reduce the load of nephrotoxic light chains seems to offer limited additional benefit in patients requiring dialysis when treated with bortezomib-based therapies (Cook M et al EHA 2016, Abs P270). However, outside clinical trials, there are limited data focusing on the management and outcomes of NDMM patients requiring dialysis. Thus, we analyzed the outcomes of consecutive newly diagnosed patients with RF requiring dialysis, who were managed and treated in a single center. Between 1995 and 2016, 50 patients (6.2% of 796 consecutive NDMM) who were treated in the Department of Clinical Therapeutics (Athens, Greece) presented with severe RF requiring dialysis. The analysis included all patients who received at least one dose of any therapy. All patients received similar supportive care and dialysis with regular filters. The median age of patients requiring dialysis was 69 years (37-88), 68% were >65 years of age. At presentation 92% had Hb <10 g/dl, 5 (10%) had platelet count <100x109/l, 12 (24%) had hypeprcalcemia (Ca ≥11.5 mg/dl) and 24 (48%) had elevated LDH (≥250 IU/l). All patients had elevated β2-microglobulin (median 21.7 mg/L, range 6-60 mg/l) and all were ISS stage 3. High risk cytogenetics (N=40) were present in 38% and per R-ISS, 75% were R-ISS-3 and 25% R-ISS-2. Myeloma was light chain only in 42%, IgA in 26%, IgG in 30% and IgD in 1 patient (2%); light chain was κ in 38 (64%) and λ in 18 (36%). Among patients who retained urine flow at presentation, median 24h Bence Jones proteinuria was 2.2 gr (range 0.1-8.8 gr). Among patients with available FLCs, median level of involved free light chain (iFLC) was 9080 mg/l (range 119-201000 mg/l). Treatment was bortezomib-based in 41 (82%) patients: 11 (22%) had bortezomib + dexamethasone (VD), 21 (42%) VD + cyclophosphamide (VCD), 8 (16%) VD + thalidomide (VTD), 1 (2%) VD + doxorubicin (PAD). Nine (18%) patients received non-bortezomib containing regimens: 5 (10%) thalidomide plus high dose dexamethasone and 4 (8%) VAD with high dose dexamethasone. Twenty-five (50%) patients became dialysis independent at a median time of 158 days from start of therapy (range 4-336 days). Age ≤65 years was associated with higher probability (75% vs 38%) and shorter time to dialysis independence (51 vs 336 days; p=0.027); no other baseline factors were associated with dialysis independence in univariate analysis. Among patients treated with bortezomib, three-drug combinations (n=30) vs VD alone (N=11) were associated with higher probability of dialysis independence (57% vs 27%; p=0.06). Among patients who became dialysis independent 12 received VCD, 4 VTD, one PAD, 3 VD, 2 MDT, 2 VAD and one T-VAD. Median follow up for all patients was 33 months and median survival was 29 months. Early mortality (within 2 months from start of therapy) was 16%, mostly due to infectious complications. On intent to treat, 64% achieved ≥PR (CR: 6%, VGPR: 32%, PR: 26%); among patients who survived >2 months, ≥PR was achieved by 76%. At 2-month landmark, patients who achieved ≥PR within the first 2 months had higher dialysis independence rates (68% vs 27%, p=0.004). Becoming dialysis independent was associated with a significant improvement in survival (median OS of 63 vs 22 months of patients who remained on dialysis; p=0.002), even after exclusion of early deaths. Notably, the survival of patients who discontinued dialysis was similar to that of the rest of patients (57 months). High dose melphalan (HDM) followed by autologous stem cell transplantation was performed in five patients while on dialysis. Four of them (80%) become dialysis independent approximately one month after HDM. In conclusion, about 6% of NDMM present with renal failure requiring dialysis but half of them can become dialysis independent after bortezomib-based therapy, without the use of special filters, especially if they achieve a rapid myeloma response. VD-based triplets increase the probability of renal response over VD alone and independence from dialysis is associated with a significant improvement in prognosis. Disclosures Dimopoulos: Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Genesis: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Terpos:Celgene: Honoraria; Genesis: Consultancy, Honoraria, Other: Travel expenses, Research Funding; Novartis: Honoraria; BMS: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Other: Travel expenses, Research Funding; Takeda: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Other: Travel expenses, Research Funding. Kastritis:Takeda: Consultancy, Honoraria; Genesis: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Janssen: Consultancy, Honoraria.

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Recovery of Renal Function and Independence from Dialysis in Newly Diagnosed and Relapsed Multiple Myeloma Patients - A Single Instituition Experience.

Blood ◽

10.1182/blood.v110.11.4847.4847 ◽

2007 ◽

Vol 110 (11) ◽

pp. 4847-4847

Author(s):

Girish Ravindranathan ◽

Tanya Indrakumar ◽

Sohail Ahmad ◽

Moez Dungarwalla ◽

Pamela Kanagasabapathy ◽

...

Keyword(s):

Multiple Myeloma ◽

Renal Failure ◽

Renal Function ◽

Renal Impairment ◽

Current Therapy ◽

High Dose ◽

Newly Diagnosed ◽

Female Ratio ◽

Male To Female ◽

Relapsed Myeloma

Abstract Background: Renal impairment occurs in up to 30% of patients who present with multiple myeloma and in up tp 50% of patients at some stage of the illness. It is known that renal impairment can be reversed in a significant number of such patients by correction of precipitating factors and rehydration but that 3–12% patients will require dialysis or other major intervention. These patient have a worse prognosis largely due to an excess of early deaths, renal failure being the major cause of death in 14% of myeloma patients and contributing factor in a further 14%. (Drayson et al UK MRC MM trials 1980–2002) We have conducted a study to look into the clinical course and outcome of all patients with renal impairment sufficiently severe to be referred to the regional renal unit in South East England between 2000 and 2007 with either newly diagnosed multiple myeloma (MM) or relapsed disease to try to identify features which predict for better outcomes. Methods: 62 patients with MM and renal failure received treatment in our hospital over the last 8 years. Patients have been assessed for recovery of renal function and dialysis independence in two groups - newly diagnosed (n=47) and relapsed patients (n=15). They were analysed separately as the disease tends to be biologically different at presentation and relapse, and therapeutic options may be different. In addition relatively little data on relapsed myeloma with renal failure is available. Results: 14 patients in the newly diagnosed group and 4 in the relapsed group were deemed unsuitable for an active treatment approach and have been excluded from statistical analysis in this paper but will be analysed separately to try to identify factors which could improve the outcome for this group. The patients with newly diagnosed MM and actively treated had a mean age of 65.3±1.7 years (range 41.9–83.3), male to female ratio of 1.7:1 and a mean peak creatinine at presentation of 684.5±60.9 mmol/l (range 107–1820). Light chain myeloma was overrepresented and was seen in 57.5% of patients (n=19). 12 (36.3%) of 33 the new patients avoided dialysis. 21 required dialysis, of whom 8 patients (38.1%) recovered function to dialysis independence at 6 months. There were only 3 deaths at 6 months follow-up. The mean age of the relapsed patients was 61.8±3.5 years (range 34.9–80.7), male to female ratio of 2.6:1 and a mean peak creatinine at presentation of 824±118.4 mmol/l (range 231–1591). Majority of myeloma was IgA in 36.3% (n = 4). Among the 11 relapsed, 82% (n=9) required dialysis but a significant proportion, 88% (n=8), were dialysis independent at 6 months There was only one death within 6 months of a relapse. Treatments in the 2 groups varied but involved the use of regimes containing high dose steroids in most patients. Conclusions: Our data suggest that renal failure and dialysis dependence can be avoided or is reversible in a large number of newly diagnosed and relapsed myeloma patients. This study of an unselected group of patients receiving current therapy provides an important baseline against which to compare the effect of approaches involving the newer biological agents.

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Analysis of Immunophenotypic Response (IR) by Multiparameter Flow Cytometry In 516 Myeloma Patients Included In Three Consecutive Spanish Trials

Blood ◽

10.1182/blood.v116.21.1910.1910 ◽

2010 ◽

Vol 116 (21) ◽

pp. 1910-1910 ◽

Cited By ~ 2

Author(s):

Bruno Paiva ◽

María-Belén Vidriales ◽

María-Angeles Montalbán ◽

María-Victoria Mateos ◽

Laura Rosiñol ◽

...

Keyword(s):

Flow Cytometry ◽

Board Of Directors ◽

Residual Disease ◽

Young Patients ◽

Novel Agents ◽

Multiparameter Flow Cytometry ◽

High Dose ◽

Newly Diagnosed ◽

Advisory Committees ◽

The Impact

Abstract Abstract 1910 The outcome of multiple myeloma (MM) patients has markedly improved in the last decade. Thus, overall response rates between 85%-95%, with 30%-50% complete remission (CR) rates are now being reported in young patients treated with novel agents plus high-dose therapy/autologous stem cell transplantation (HDT/ASCT). A similar scenario is also emerging in the elderly (non-transplant candidates) population. Accordingly, more sensitive techniques are needed to assess patients’ response; these may contribute to compare the efficacy of different treatment schemas, to monitor minimal residual disease (MRD) and for prognostication. In the present study we have assessed the frequency and the prognostic value of IR by multiparameter flow cytometry in a total of 516 newly diagnosed MM patients included in three consecutive PETHEMA/GEM Spanish trials: two designed for transplant candidate patients - GEM 2000 (n=157) and GEM2005<65y (n=206) - and one for elderly patients - GEM2005>65y (n=153). The GEM2000 trial was based on 6 induction cycles of VBMCP/VBAD followed by HDT/ASCT; the GEM2005<65y included three arms with 6 cycles each (Thalidomide/Dexamethasone -TD-, Bortezomib/Thalidomide/Dexamethasone -VTD- and, VBMCP/VBAD with Bortezomib in the two final cycles -VBMCP/VBAD/Bortezomib) followed by HDT/ASCT; and the GEM2005>65y compared 6 cycles of Bortezomib/Melphalan/Prednisone -VMP- vs. Bortezomib/Thalidomide/Prednisone -VTP-. All three trials had in common that patients received 6 induction cycles and IR was evaluated at this time point. In addition, IR was assessed on day +100 after HDT/ASCT in the first two trials. Patients were defined to be in IR when myelomatous plasma cells (MM-PCs) were undetectable by MFC or when less than one phenotypically aberrant PC was detected among 104 cells analyzed. Patients were referred for MRD studies if they were mainly in CR or VGPR. The IR rates reported here were calculated on intention to treat analysis. Figure 1 summarizes the IR rates after induction. The lowest IR rates corresponded to the VBMCP/VBAD and TD schemes (5% and 6%, respectively) while with the bortezomib-based regimens an approximately 3-fold increment in the IR rates was observed: VTP (12%), VBMCP/VBAD/Bortezomib (15%), VMP (16%) and VTD (17%). After HDT/ASCT, IR rates were found to be significantly increased (p<.001) in the GEM2000 protocol (14%) and in all arms of the GEM2005<65y trial: TD (18%), VBMCP/VBAD/Bortezomib (30%) and VTD (34%). Thus, a minimum 2-fold increment of IR rates was further achieved after HDT/ASCT. In addition, IR rates achieved after HDT/ASCT in patients included in all three arms of the GEM2005<65y trial were significantly superior (p≤.008) to cases treated according to the GEM2000 protocol, indicating that induction regimens with novel agents improved post-transplantation rates of IR. Moreover, bortezomib-based regimens vs. TD were associated with increased IR rates not only before but also after HDT/ACSCT (p=.06 and p=.02 for VBMCP/VBAD/Bortezomib and VTD, respectively). We further compared the impact of achieving an IR after induction and at day+100 after HDT/ASCT in the progression-free (PFS) and overall survival (OS) within the three protocols. Patients in IR status after an induction regimen according to the GEM2000, GEM2005<65y and GEM2005>65y protocols showed significantly longer (p<.001) 3-year PFS rates (100%, 100% and 90%, respectively) compared to patients in a no-IR status (61%, 59% and 35%, respectively). Similarly, 3-year OS rates were significantly longer (p=.01) in IR vs. no-IR patients status (100%, 100% and 94% vs. 84%, 90% and 76% for the GEM2000, GEM2005<65y and GEM05>65y protocols, respectively). Likewise, an IR vs. no-IR status after HDT/ASCT in both the GEM2000 and GEM05<65y trials was also associated with significantly increased 3-year PFS (p<.001) and OS (p=.007) rates. In summary, this study demonstrates that the achievement of an IR is a strong prognostic factor regardless of the type of treatment; thus, higher IR rates may help to identify optimal therapeutical schemes. In this sense, HDT/ASCT is able to markedly increase IR rates after induction even in the era of novel agents, and this translates into extended survival. Disclosures: Off Label Use: VTP is not approved for the treatment of newly diagnosed myeloma patients and VT and VP are not approved for maintenance therapy. None of the combinations proposed, VBCMP/VBAD plus bortezomib, VT and VTD are approved as induction therapy in newly diagnosed myeloma patients. Mateos:Janssen Cilag: Honoraria; Celgene: Honoraria. Rosiñol:Janssen-Cilag: Honoraria; Celgene: Honoraria. Cibeira:Janssen-Cilag: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees. Oriol:Janssen-Cilag: Honoraria; Celgene: Honoraria. de Arriba:Janssen-Cilag: Honoraria; Celgene: Honoraria. Palomera:Janssen Cilag: Honoraria. De La Rubia:Janssen-Cilag: Honoraria; Celgene: Honoraria. Díaz-Mediavilla:Janssen-Cilag: Honoraria; Celgene: Honoraria. Garcia-Laraña:Janssen Cilag: Honoraria; Celgene: Honoraria. Sureda:Janssen-Cilag: Honoraria; Celgene: Honoraria. Alegre:Janssen-Cilag: Honoraria; Celgene: Honoraria. Blade:Janssen cilag: Honoraria; Celgene: Honoraria. Lahuerta:Janssen-Cilag: Honoraria; Celgene: Honoraria. San Miguel:Janssen-Cilag: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Millennium: Honoraria, Membership on an entity's Board of Directors or advisory committees.

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