Melphalan/prednisone/lenalidomide (MPR) versus high-dose melphalan and autologous transplantation (MEL200) plus lenalidomide maintenance or no maintenance in newly diagnosed multiple myeloma (MM) patients.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 8509-8509 ◽  
Author(s):  
Mario Boccadoro ◽  
Federica Cavallo ◽  
Francesca Maria Gay ◽  
Francesco Di Raimondo ◽  
Arnon Nagler ◽  
...  
Keyword(s):  
Maintenance Therapy ◽  
Autologous Transplantation ◽  
Previous Treatment ◽  
New Drugs ◽  
High Dose ◽  
Risk Of Progression ◽  
Treatment Paradigm ◽  
High Dose Melphalan ◽  
To Receive

8509 Background: The incorporation of new drugs into induction, consolidation, and maintenance therapy is changing the treatment paradigm of MM. Methods: At diagnosis, 402 pts (< 65 years) were randomly assigned to receive six MPR cycles (N=202) or tandem MEL200 (N=200). After MPR or MEL200, pts were further randomized, within each group, for no maintenance (N=204) or lenalidomide maintenance (N=198). A 2x2 factorial randomized trial was designed. The primary end point was PFS. An enrolment of 170 pts/arm was required to demonstrate a 15% improvement of PFS at 2 years (2-sides a = 0.05, 1- β 80%). Results: After a median follow-up of 45 mos from diagnosis, the median PFS was 25 mos with MPR and 39 mos with MEL200 (p=.0002). Median PFS were 37.5 mos for maintenance and 25.7 mos for no maintenance (p=.0008). The 4-year OS from diagnosis was 71% with MPR and 72% with MEL200 (p=0.71), 76% for maintenance and 68% for no maintenance (p=.08). After a median follow-up of 32 mos from start of maintenance, the median PFS was for 41 mos for maintenance and 18 mos for no maintenance (p<.0001). The 3-year OS from start of maintenance was 81% for maintenance and 72% for no maintenance (p=.04). Conclusions: MEL200 significantly prolonged PFS in comparison with MPR. Lenalidomide maintenance significantly reduced the risk of progression independently from the previous treatment. OS is similar between MPR and MEL200, with a trend for an improved OS in pts receiving lenalidomide as maintenance therapy. Clinical trial information: NCT00551928. [Table: see text]

Six Years of Experience and Outcome with Maintenance Therapy with Very Low Dose Thalidomide after Auto-SCT in Multiple Myeloma

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5208-5208
Author(s):  
Vincenzo Mettivier ◽  
Luca Pezzullo ◽  
Stefano Rocco ◽  
Olimpia Finizio ◽  
Pellegrino Musto ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Maintenance Therapy ◽  
Low Dose ◽  
Autologous Transplantation ◽  
Haematological Toxicity ◽  
New Drugs ◽  
Cell Leukaemia ◽  
High Dose

Abstract New drugs and high dose therapy with auto-transplantation (auto-SCT) has improved prognosis of multiple myeloma (MM). New drugs are promising in upfront therapy while the role of maintenance is still debated. Thalidomide (thal) is an active drug in the treatment of myeloma, and is been investigated as first line therapy, the limit of this drug is the toxicity dependent dose and this determines a poor compliance. It could be useful in the control of minimal residual disease. We used low dose of thal as maintenance after autologous transplantation in patient with MM from January 2002 and here we bring our experience after six years of observation. From January 2002 to August 2008 17 patients (8 males and 9 females) with MM have been treated in our institution. Median age was 59,5 years (range 48–72). 10 were IgG, 3 IgA, 3 light chains and 1 plasma-cell leukaemia. Treatment was 4 cycles of VAD regimen followed by auto-SCT. 4/17 performed double auto-SCT. Three months after SCT these patients has begun the maintenance with thal 50 mg/die, to start thal maintenance 9 patients were in CR, 5 in PR and 3 in resistant disease and the median somministration of thal has been of 12 months (range 3–24 months). Median follow up from the beginning of maintenance therapy was 40 months (range 4–76) with 11/17 (64%) patients in CR or stable disease, with progression free survival (PFS) and overall survival (OS) projected at 75 months respectively of 53% and 51% from to start thal. In our experience we have observed a neurological toxicity (grade I–III) in the 65% of the patients but only 4 have had to suspend the treatment; a haematological toxicity of grade I in the 55% of the patients that have not behaved interruption of the treatment and finally in any case we have documented thrombotic episodes. Finally we have compared this group of patients with another group (18 patients) with the same clinical characteristics that we have observed in the same period but that have not effected maintenance with thal. In this last group 13/18 patients (72%) relapsed with median follow-up of 36 months (range 14–75) and median PFS and OS of 16 and 30 months respectively. The difference between the 2 groups is statistically significant for PFS (p: 0.003) and OS (p: 0.04). The median overall survival observed after progression, in the two groups, has been of 13 months in thal group and 17 months in the group of patients that have not effected the maintenance, this difference is not statistically different (p:0.06). In conclusion in 6 years of observation our experience has shown, even if the number of the patients is small, that maintenance with low doses of thal, after auto-transplantation, it not only has a good compliance but it improves the PFS and OS in this cohort and it doesn’t worsen the OS from the relapse.

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.

Phase I-II Trial of Tandem Autologous Transplantation with Melphalan Followed by Total Marrow Irradiation Ablative Therapy in Patients with Responding or Stable Mutiple Myeloma.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3151-3151 ◽  
Author(s):  
George Somlo ◽  
Paul Frankel ◽  
Ricardo Spielberger ◽  
Chatchada Karanes ◽  
Amrita Krishnan ◽  
...  
Keyword(s):  
Overall Survival ◽  
Autologous Transplantation ◽  
Progression Free Survival ◽  
High Dose ◽  
Ablative Therapy ◽  
Total Marrow Irradiation ◽  
Total Body ◽  
Grade 3 ◽  
High Dose Melphalan

Abstract Abstract 3151 Background: Ablative dose total body irradiation (TBI) of 800 cGy in combination with high-dose melphalan (MEL) as part of single cycle autologous transplantation (AT) was found to be too toxic, and therefore inferior, in comparison to MEL. We set out to test total marrow irradiation, (TMI), a “sculpted” form of targeted total body irradiation using image-guided intensity modulated helical tomotherapy, given as the sole ablative regimen during the second cycle of tandem AT (TAT) as consolidation in patients with stable/responsive myeloma. Patients and Methods: Patients with Durie-Salmon stages I-III multiple myeloma in response or with stable disease, who were ≤ 70 years old and within 18 months from diagnosis, were enrolled. Patients received MEL 200 mg/m2 and AT (cycle 1), and, following recovery, TMI and AT were administered (cycle 2) at a median of approximately 2 months after the first AT. During the phase I part, TMI was tested between 1000 cGy and 1800 cGy given twice daily × 5 days. The maximum tolerated dose (MTD) –as previously reported- was established at 1600 cGy [Somlo et al. Clin Cancer Res. 2011; 17 (1):174–82]. Following cycle 2 of TAT, maintenance therapy consisted of dexamethasone 40 mg/day × 4 days and an IMiD (first thalidomide, and during the phase II portion, lenalidomide) in a 28-day cycle, administered for 6 cycles for patients in complete response (CR), or for a minimum of 12 cycles for pts not in CR. Results: 54 patients were enrolled (23 females, 31 males). The median age was 54.2 years (range 31.5–66.9). All patients with stage I (7), II (14), III (n=33) multiple myeloma received MEL. Forty-three patients (79.6%) received TMI, 30 at the MTD (6 enrolled at the MTD did not receive TMI). Reversible grade 3 non-hematologic toxicities following TMI at the MTD included febrile neutropenia (5/30), electrolyte abnormalities (7/30), sepsis/infection (5/30), anorexia (2/30), nausea/vomiting (2), fatigue (1), syncope (1). Grade 3 late toxicities include 1 case each of fatigue, nausea, 1 myositis and transaminitis. There were no primary or secondary graft failures, or second malignancies. Of the entire cohort of 54 patients, by intent to treat analysis best responses following TAT included CR (n: 20), very good partial response (VGPR, n:11), partial response (PR, n:16). At a median follow-up of 39 months from first AT, progression-free survival is 55% (95% CI 42–73%) and overall survival is 81% (95% CI 70–94%). For patients treated at the MTD of TMI 1600 cGy, at a median follow-up of 39 months from the first AT, progression-free survival (PFS) is 66% (50–88%), and overall survival (OS) is 80% (65–99%). Conclusion: TMI of 1600 cGy is feasible as ablative therapy following recovery from high-dose melphalan and AT. CR and VGPR rates are expected to improve with time on maintenance therapy and such data as well as progresion-free and overall survival will be updated. Safety and progression-free and overall survival data are encouraging, and further assessment of the role of TMI is warranted in combination with MEL as part of either single AT, part of TAT, or in comparison of tandem versus single ablative therapy, both in the upfront, and salvage settings. Disclosures: Off Label Use: IMiDs as maintenance.

scholarly journals Long-term follow-up of a comparison of nonmyeloablative allografting with autografting for newly diagnosed myeloma

Blood ◽  
2011 ◽  
Vol 117 (24) ◽  
pp. 6721-6727 ◽  
Author(s):  
Luisa Giaccone ◽  
Barry Storer ◽  
Francesca Patriarca ◽  
Marcello Rotta ◽  
Roberto Sorasio ◽  
...  
Keyword(s):  
Complete Remission ◽  
New Drugs ◽  
High Dose ◽  
Newly Diagnosed ◽  
Term Survival ◽  
Free Survival ◽  
Long Term Follow Up ◽  
High Dose Melphalan

Abstract Before the introduction of new drugs, we designed a trial where treatment of newly diagnosed myeloma patients was based on the presence or absence of HLA-identical siblings. First-line treatments included a cytoreductive autograft followed by a nonmyeloablative allograft or a second melphalan-based autograft. Here, we report long-term clinical outcomes and discuss them in the light of the recent remarkable advancements in the treatment of myeloma. After a median follow-up of 7 years, median overall survival (OS) was not reached (P = .001) and event-free survival (EFS) was 2.8 years (P = .005) for 80 patients with HLA-identical siblings and 4.25 and 2.4 years for 82 without, respectively. Median OS was not reached (P = .02) and EFS was 39 months (P = .02) in the 58 patients who received a nonmyeloablative allograft whereas OS was 5.3 years and EFS 33 months in the 46 who received 2 high-dose melphalan autografts. Among patients who reached complete remission in these 2 cohorts, 53% and 19% are in continuous complete remission. Among relapsed patients rescued with “new drugs,” median OS from the start of salvage therapy was not reached and was 1.7 (P = .01) years, respectively. Allografting conferred a long-term survival and disease-free advantage over standard autografting in this comparative study.

A Prospective, Randomized Study of Melphalan, Prednisone, Lenalidomide (MPR) versus Melphalan (200 Mg/M2) and Autologous Transplantation (Mel200) in Newly Diagnosed Myeloma Patients: An Interim Analysis.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 350-350 ◽  
Author(s):  
Antonio Palumbo ◽  
Federica Cavallo ◽  
Dina Ben Yehuda ◽  
Paola Omedè ◽  
Agostina Siniscalchi ◽  
...  
Keyword(s):  
Overall Survival ◽  
Autologous Transplantation ◽  
Progression Free Survival ◽  
New Drugs ◽  
Thromboembolic Events ◽  
Free Survival ◽  
Cd34 Cells ◽  
Grade 3 ◽  
To Receive

Abstract Abstract 350 Background. The incorporation of new drugs as induction therapy before autologous transplantation appears to produce a high proportion of complete responses, slightly superior to those achieved by conventional chemotherapy with new drugs. Randomized trials are needed to directly compare current best chemotherapeutic approach with best autologous transplantation strategy. Aims. To compare melphalan, prednisone and lenalidomide (MPR) with tandem melphalan (200 mg/m2) (MEL200) in patients younger than 65 years. Methods. As induction, all (N=402) patients received four 28-day cycles of lenalidomide (25 mg days 1-21) and low-dose dexamethasone (40mg days 1,8,15,22) (Rd). Cyclophosphamide (4 g/m2) plus granulocyte-colony stimulating factor was used to mobilize stem cells. As consolidation, patients (N=202) randomized to MPR received six 28-day cycles of melphalan (0.18 mg/kg days 1-4), prednisone (2 mg/kg days 1-4) and lenalidomide (10mg days 1-21); patients (N=200) randomized to MEL200 received tandem melphalan 200 mg/m2 with stem-cell support. All patients were also randomized to receive either aspirin or low-molecular weight heparin (enoxaparin) as thromboprophylaxis. Primary end point was progression-free survival; data were analyzed in intention-to-treat. Results. Patient characteristics were similar in both groups, median age was 58 years. After Rd induction, at least partial response (PR) rate was 84%, at least very good partial response (VGPR) was 32% including 5% complete response (CR). The median yields of CD34+ cells harvested was 10 ×106 CD34+ cells/Kg; 94% of patients collected the minimum dose of 2×106/kg CD34+ cells. After 3 cycles of MPR, at least VGPR rate was 51% and CR 11%. After the first MEL200, at least VGPR rate was 56% and CR 14%. No difference in responses were reported according to cytogenetic abnormalities, such as del13, t(4;14) and t(14;16). After a median follow-up of 12 months, 1-year progression-free survival was 96% for MPR and 94% for MEL200 (p=.92) 1-year overall survival was 98% for MPR and 99% for MEL200 (p=.94). During Rd induction, the most frequent grade 3-4 adverse events were neutropenia (9%), anemia (8%), infections (4%), skin rash (4%), fatigue (2%) and thromboembolic events (1%). During consolidation, the incidence of grade 3-4 neutropenia (97% vs 34%, p <.001) thrombocytopenia (97% vs 16%, p<.001), infections (21% vs 3%, p<.001) and gastrointestinal (17% vs 1%, p<.001) complications was higher in MEL200 patients The incidence of thromboembolic events was similar in patients randomized to receive aspirin (2%) or enoxaparin (1%) as thromboprophylaxis (p=.42). Conclusion. Rd is an effective and safe induction regimen. Both MPR andMEL200 improved the quality of response, achieved by Rd induction. At present, progression-free and overall survival are not significantly different in the two groups, but longer follow-up is needed. Both aspirin and enoxaparin were equally effective as thromboprophylaxis. These data will be updated at the meeting. Disclosures: Palumbo: CELGENE: Honoraria. Cavallo:CELGENE: Honoraria. Patriarca:CELGENE: Honoraria. Caravita:CELGENE: CONSULTANCY. Boccadoro:CELGENE: CONSULTANCY, ADVISORY COMMITTEES, Research Funding.

Busulfan / Melphalan / Bortezomib (Bu-Mel-Vel) Vs. High Dose Melphalan As Conditioning Regimen For Autologous Hematopoietic Cell Transplantation In Multiple Myeloma (MM)

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3357-3357 ◽  
Author(s):  
Tulio E. Rodriguez ◽  
Parameswaran Hari ◽  
Patrick J Stiff ◽  
Xiaobo Zhong ◽  
Danielle Sterrenberg ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Maintenance Therapy ◽  
Cell Transplantation ◽  
Research Funding ◽  
Hematopoietic Cell Transplantation ◽  
Conditioning Regimen ◽  
High Dose ◽  
High Dose Melphalan ◽  
Autologous Hematopoietic Cell Transplantation

Abstract Background High dose melphalan (MEL) preceding autologous hematopoietic cell transplantation (HCT) for MM continues to be the standard of care. No regimen has been clearly proven superior to MEL 200 mg/m2 (MEL 200). The combination of Busulfan (Bu) and MEL was shown to improve progression free survival (PFS) (Lahuerta, et al; Haematologica. 2010 Nov; 95 (11):1913-20). The combination of bortezomib (Vel) with MEL also demonstrated superior PFS vs. MEL alone using historical controls (Roussel et al; Blood. 2010; 115:32-7). We studied a conditioning regimen combining Bu, MEL and Vel (BuMelVel) in an open label phase II study aimed at improving PFS after HCT for MM. To assess the potential value of this novel regimen, we performed a comparative analysis between BuMelVel and a cohort of patients conditioned with MEL 200 from the Center for International Blood and Marrow Transplant Research (CIBMTR) database. Methods Between July 2009 and May 2012, 43 eligible patients received BuMelVel conditioning followed by HCT. Bu was administered daily intravenous (IV) for a total of 4 days with the first 2 days (day -6, -5) at fixed dose of 130 mg/m2 over 3 hours and the subsequent 2 doses (day -4, -3) adjusted to achieve a target area under the concentration-time curve (AUC) total of 20,000 mM* min by performing pharmacokinetic (PK) analysis after the first dose of IV Bu. Mel 140 mg/m2 and Vel 1.6 mg/m2 were administered IV on Day-2 and Day -1 respectively. Outcomes were compared with a contemporaneous North American cohort (n=162) receiving single agent MEL 200 conditioning from the CIBMTR database. Controls were matched on age, sex, Karnofsky performance status (KPS), stage and interval from diagnosis to HCT. Multivariate analysis of Relapse, PFS, and overall survival (OS) was performed. Median follow up of survivors was 25 months. Planned maintenance therapy was not used. Results Age, gender, KPS, isotype, and stage were similar between groups (Table 1.). The MEL 200 cohort had more standard risk patients per Mayo Stratification of Myeloma and Risk-Adapted Therapy (mSMART) (78% vs. 40% in BuMelVel, p <0.0001) and more patients with only 1 prior line of therapy pre-HCT (67% vs. 47%, p = 0.02). Platelet and neutrophil engraftment kinetics were similar. Veno-occlusive disease (VOD) was not observed in the BuMelVel group and there was no non-relapse mortality (NRM). The incidence of relapse and PFS at 1 year were superior in the BuMelVel cohort (Table 1.). OS was similar between the cohorts. In multivariate analysis, PFS was superior in the BuMelVel cohort (HR for relapse/death in MEL 200 =1.87, p=0.04). Lack of a very good partial response or higher (≥VGPR) prior to HCT was associated with inferior PFS whereas lower KPS (<80) and higher international stage were associated with mortality. Conclusion PK directed dosing of Bu can be safely combined with Mel 140 followed by bortezomib without higher risk of VOD or NRM and in the absence of maintenance therapy. Within the constraints of a short follow up and uncontrolled post-transplant salvage therapies on both groups, no difference in OS has yet been observed. This novel conditioning regimen is safe and was associated with superior PFS compared with similarly matched controls and warrants further testing. Disclosures: Rodriguez: Otsuka: Research Funding; Millennium: Research Funding, Speakers Bureau; Celgene: Honoraria, Speakers Bureau. Vesole:Millennium: Speakers Bureau.

Long-Term Outcomes of Autologous Transplantation in Multiple Myeloma: Benefit from the Newer Drugs Used in the Relapsed Setting.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3331-3331 ◽  
Author(s):  
Roman Hajek ◽  
Marta Krejci ◽  
Vlastimil Scudla ◽  
Elena Tothova ◽  
Martin Mistrik ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Slovak Republic ◽  
Autologous Transplantation ◽  
Conditioning Regimen ◽  
High Dose ◽  
Term Survival ◽  
Bortezomib Treatment ◽  
High Dose Melphalan

Abstract Background: Autologous stem cell transplantation (ASCT) plays an important role in the treatment of multiple myeloma (MM) patients (pts). In this report, we describe the longterm outcome of cohort of 185 pts with newly diagnosed symptomatic MM treated with ASCT. Median follow-up from the start of therapy was 102.8 months (range 67.2–150.4). We have specifically analyzed benefit from the newer drugs used in the relapsed setting. Methods: A total of 185 MM pts underwent ASCT in the clinical trial 4W of Czech Myeloma Group in 18 centres in Czech Republic and Slovak Republic between 1996 and 2001. The conditioning regimen was high dose melphalan (200mg/m2) in all pts. At diagnosis of MM 72.4% (134/185) of pts had stage III according to Durie- Salmon, 18.4% (34/185) stage II and 9.2% (17/185) stage I. Clinical stages according to ISS were the following: stage 1 in 42.5% (74/174) of pts, stage 2 in 36.8% (64/174) and stage 3 in 20.7% (36/174) pts. Types of monoclonal immunoglobulin were as following: 67.6% (125/185) IgG, 21.1% (39/185) IgA, 9.7% (18/185) light chain, 1.6% (3/185) IgD. Renal insufficiency was presented in 5.9% (11/185) of pts. Median age at transplantation was 54.8 years (range: 28.3–69.2). When the symptomatic relapse of MM after ASCT was occurred, 34.6% (45/130) of pts were treated by conventional chemotherapy (CC) alone, 22.3% (29/130) by thalidomide based regimen, 10.7% (14/130) by bortezomib based regimen, 22.3% (29/130) pts underwent re-transplantation and 10% (13/130) of pts received combination of newer drugs and re-transplantation. Results: Following ASCT, overall response rate (ORR) was 93.5% (173/185), 29.2% (54/185) of pts were in CR, 38.4% (71/185) of pts were in VGPR, 25.9% (48/185) of pts in PR. Median of overall survival (OS) from start of treatment was 77.9 months (9.6 – 147.3), median of TTP was 39.8 months (7.0–146.9). Total of 23.2% (43/185) of pts are alive and disease free, 20.5% (38/185) of pts are alive with relapse and 56.3% (104/185) of pts died with median follow-up 8.3 years from the start of therapy. Significant prognostic parameters for better OS after ASCT were: ISS stage < III (p<0.001), achievement of CR after ASCT (p<0.001) and the use of the newer drugs in the relapsed setting. Patients treated with thalidomide and/or bortezomib comparing to pts treated with CC only had significantly longer survival (p<0.001). Patients treated with re-transplantation only had not better OS (46.1 vs 37.8 months; p=0.224) comparing to pts treated with CC. In opposite, pts treated with the newer drugs and re-transplantation had better prognosis (OS 85.7 vs 37.8 months; p<0.001) than pts treated by CC. In multivariate analysis thalidomide and/or bortezomib treatment in the relapse was the strongest factor for long-term survival (beta 1.988; beta (exp) 7.303; CI: 2.860–18.645; p<0.001) Conclusion: ASCT is effective procedure in MM pts. The achievements CR after transplantation, no presence of stage 3 according to ISS were significant parameters for long-term postransplant survival. Accessibility of the thalidomide and bortezomib was independent of other prognostic factors. The use of the newer drugs in the relapsed setting significantly improved prognosis of patients.

scholarly journals Long-Term Follow up of a Comparison of Non-Myeloablative Allografting with Autografting for Newly Diagnosed Myeloma

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 525-525 ◽  
Author(s):  
Benedetto Bruno ◽  
Barry Storer ◽  
Francesca Patriarca ◽  
Marcello Rotta ◽  
Roberto Sorasio ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Salvage Therapy ◽  
Research Funding ◽  
New Drugs ◽  
High Dose ◽  
Advisory Committees ◽  
Term Survival ◽  
High Dose Melphalan

Abstract Abstract 525 Background: Role and timing of allografting in myeloma are hotly debated. Before the introduction of new drugs, we carried out a trial where the treatment assignment was based only on the presence/absence of an HLA-identical sibling (Bruno et al, N Engl J Med 2007). Methods: Overall, 162/199 (81%) of patients with at least one sibling were HLA-typed. First-line treatments included induction with VAD-based regimens and a cytoreductive autograft, followed by a nonmyeloablative allograft (Tandem auto-allo) or a second melphalan-based autograft (Double-auto). We now report an update at a median follow up of 7.1 years. Results: Response rates [complete (CR) and partial remissions (PR)] at the time and after the non-myeloablative allograft and at the time and after the second autograft did not differ between the two cohorts: 76% and 86%, and 76% and 91% respectively (p=1 and p=0,54). However, CR rate was significantly higher after the non-myeloablative allograft than after the second autograft: 55% versus 26% (p=0,0026). At a median follow up of 7.1 years (range 2.5 – 10.7+), by intention-to-treat analysis, median overall survival (OS) and event free survival (EFS) were significantly longer in patients with HLA-identical siblings (No.80) as compared with those without (No.82): not reached vs. 4.25 years (HR 0.51, CI 95% 0.34–0.76, p=0.001) and 2.8 vs. 2.4 years (HR 0.62, CI 95% 0.44–0.87, p=0.005). By multivariate analysis, independent of age, gender, myeloma protein isotype, Durie&Salmon stage, and disease status at the first autograft; the presence of an HLA-identical sibling was significantly associated with longer OS (HR 0.5, CI 95% 0.3–0.8, p=0.001) and EFS (HR 0.63, CI 95% 0.4–0.9, p=0.01). At a median follow up of 7.3 (range 5.4 – 10.7+ years), median OS was not reached in the 58 patients who received a non-myeloablative allograft and 5.3 years in the 46 who received a second high-dose melphalan autograft (HR 0.55, CI 95% 0.32–0.94, p=0.02), whereas EFS was 39 months and 33 months (HR 0.62, CI 95% 0.40–0.96, p=0.02) respectively. Cumulative incidence of transplant related mortality was 11% and 2% at 2 years respectively. At median follow-ups of 7.3 years from diagnosis (range 5.4 – 10.4+) and 6.5 years from the allograft (range 4.2 – 9.4+), and 7.4 years from diagnosis (range 5.6 – 10.7+) and 6.2 years from the second autograft (range 4.7 – 9.1+), 30/58 (52%) and 37/46 (80%) patients, respectively, were treated for disease relapse/progression. Salvage therapies included bortezomib- or thalidomide-containing regimens in most patients of both cohorts. After 1–3 lines of therapy, 22/30 (73%) had a response, including 5 CR and 17 PR, in the tandem auto-allo group, whereas 21/37 (54%) had a response, including 4 CR and 16 PR after the second autograft. Of note, at a median follow up of 3.9 years from the start of the first salvage therapy, OS was not reached and was 1.7 years in patients who had relapsed/progressed after the allograft and the second high-dose melphalan (HR 0.44, CI 95% 0.24–0.82, p=0.01) respectively. Conclusions: In this study, allografting conferred a long term survival advantage over standard autografting. Salvage therapy was associated with longer OS perhaps due to a synergistic effect between new drugs and residual graft-vs.-myeloma effects. In prospective clinical trials, the combination of graft-vs.-myeloma effects with “new drugs” should be explored and may increase the cure rate of myeloma patients. Disclosures: Bringhen: Celgene: Honoraria; Janssen-Cilag: Honoraria. Palumbo:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen-Cilag: Honoraria, Membership on an entity's Board of Directors or advisory committees. Boccadoro:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen-Cilag: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding.

scholarly journals Treatment of Polycythemia Vera: Use of 32P Alone or in Combination With Maintenance Therapy Using Hydroxyurea in 461 Patients Greater Than 65 Years of Age

Blood ◽  
1997 ◽  
Vol 89 (7) ◽  
pp. 2319-2327 ◽  
Author(s):  
Yves Najean ◽  
Jean-Didier Rain
Keyword(s):  
Life Expectancy ◽  
Maintenance Therapy ◽  
Maintenance Treatment ◽  
Low Dose ◽  
Vascular Complications ◽  
Vascular Risk ◽  
Risk Of Progression ◽  
The Mean ◽  
Continuous Use ◽  
To Receive

Abstract Despite myelosuppression, polycythemic (PV) patients greater than 65 years of age have a high risk of vascular complications, and the leukemic risk exceeds 15% after 12 years. Is the addition of low-dose maintenance treatment with hydroxyurea (HU) after radiophosphorus (32P) myelosuppression able to decrease these complications? Since the end of 1979, 461 patients were randomized to receive (or not) low-dose HU (5 to 10 mg/kg/d), after the first 32P-induced remission, and were observed until death or June 1996. Maintenance treatment very significantly prolonged the duration of 32P-induced remissions and reduced the annual mean dose received to one-third. However, despite this maintenance, 25% of the patients had an excessive platelet count and the rate of serious vascular complications was not decreased, except in the most severe cases with short-term relapse of polycythemia. Furthermore, the leukemia rate was significantly increased beyond 8 years and a significant excess of carcinomas was also observed. The continuous use of HU did not decrease the risk of progression to myelofibrosis (incidence of 20% after 15 years). Life expectancy was shorter (a median of 9.3 years v 10.9 years with 32P alone), except in the most severe cases (initial 32P-induced remission lasting &lt;2 years) in which maintenance treatment moderately prolonged the survival by reducing the vascular risk. In most cases of PV, in which the duration of the first 32P-induced remission exceeded 2 years, the introduction of HU maintenance did not reduce the vascular risk. Although it considerably decreased the mean dose of 32P received, HU maintenance therapy significantly increased the leukemia and cancer risks and reduced the mean life expectancy by 15%. However, in cases with more rapid recurrence, the introduction of maintenance treatment reduced the vascular risks and moderately prolonged survival. The use of HU as a maintenance therapy is therefore only justified in this situation.

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