Clinical Implications of t(11;14)(q13;q32), t(4;14)(p16.3;q32) and -17p13 (p53) Deletions in Myeloma Patients Treated with High Dose Therapy.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 334-334
Author(s):  
Morie Abraham Gertz ◽  
Martha Q. Lacy ◽  
Angela Dispenzieri ◽  
Philip R. Greipp ◽  
Mark R. Litzow ◽  
...  
Keyword(s):  
Cox Model ◽  
Multivariable Analysis ◽  
Clinical Importance ◽  
High Dose ◽  
Therapeutic Approaches ◽  
Time To Progression ◽  
High Dose Therapy ◽  
Dose Therapy ◽  
Conventional Cytogenetics ◽  
The Impact

Abstract Introduction: FISH is able to recognize chromosomal deletions and translocations with a greater sensitivity than conventional cytogenetics. Specific abnormalities have been associated with prognosis. Initial observations suggest a poor outcome for patients with -17p13.1, chromosome 13 abnormalities (Δ13) and t(4;14)(p16.3;q32). In contrast a good outcome has been shown in some series for patients with t(11;14)(q13;q32). We analyzed the value of FISH in patients receiving high dose therapy . Patients and Methods: We studied by cIg-FISH 226 patients undergoing high dose therapy at Mayo Clinic between 1/1990 and 9/2001. All patients had a pretransplant cIg-FISH done on cytospin slides from marrow aspirates for t(11;14)(q13;q32), t(4;14)(p16.3;q32), and -17p13.1(p53). Information was available regarding Δ13 for all patients (+ in 52%). Results: The prevalence of the abnormalities were: t(11;14)(q13;q32) 17% (n=197), t(4;14)(p16.3;q32) 13% (n=153), and -17p13.1 11% (n=168). The overall survival (OS)was significantly shortened in patients with t(4;14)(p16.3;q32) (18.2 vs. 43.3 mo, p=0.001) (figure) and patients with -17p13.1 (14.7 vs. 38.6 mo, p=.01). OS was not different for patients with the t(11;14)(q13;q32) (36.2 vs. 34.8 mo, p=ns). Likewise time to progression (TTP) was shortened in patients with t(4;14)(p16.3;q32) (8.5 vs 17.7 mo, p=.001) and -17p13.1 (8.3 vs. 16.2 mo, p=0.005). TTP was also not affected significantly by the t(11;14)(q13;q32) (20.7 vs. 14.9 mo, p=NS). To dissect the specific contribution of t(4;14)(p16.3;q32) we did a subset analysis of patients who also had Δ13, since 85% of patients with t(4;14)(p16.3;q32) are expected to have Δ13. Of 84 studied for both abnormalities 22 had both Δ13 and t(4;14)(p16.3;q32). The OS was significantly shorter in patients with both abnormalities versus those with Δ13 alone (26.6 vs. 18.2 months, p=0.001). When a multivariable analysis of the impact of Δ13 and t(4;14)(p16.3;q32) were placed into a Cox model the hazard function for t(4;14)(p16.3;q32) was greater than Δ13 (2.6 versus 1.6). Δ13 had only borderline significance in this model (p=0.06). Conclusion: We have been unable to corroborate the improved outcome after transplant for patients with t(11;14)(q13;q32). As has been reported in patients with conventional and high dose therapy -17p13(p53) and t(4;14)(p16.3;q32) have clinical importance for estimation of OS and TTP. In this patient group the t(4;14)(p16.3;q32) carried a greater adverse impact than did Δ13, and identifies a subset of patients whose time to progression is 8.5 months. These patients likely do not benefit from autologous transplant and are candidates for novel therapeutic approaches. Outcome Successful determination Patients with translocation or deletion Survival (months) with/without abnormality Time to Progression (months) with/without abnormality * p<0.01;**p<0.001 t(11;14)(q13;q32) 197 34(17%) 36.2/34.8 20.7/14.9 p53 168 18(11%) 14.7/38.6 * 8.3/16.2 * t(4;14)(p16.3;q32) 153 26(17%) 18.2/43.3 **figure 8.5/17.7 ** t(4;14)(p16.3;q32)/Δ13+ patients 84 22(26%) 18.2/26.6 8.2/12.8 * Figure Figure

Evaluation of the Impact of Three Different Pre-Transplant Strategies On the Outcome of Myeloma Patients Candidates to High-Dose Therapy.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1223-1223
Author(s):  
Alessandro Corso ◽  
Silvia Mangiacavalli ◽  
Luciana Barbarano ◽  
Annalisa Citro ◽  
Paola Brasca ◽  
...  
Keyword(s):  
Patient Flow ◽  
High Dose ◽  
High Dose Therapy ◽  
Dose Therapy ◽  
Oral Dexamethasone ◽  
Group 3 ◽  
Group 2 ◽  
The Impact ◽  
Group 1

Abstract Abstract 1223 Poster Board I-245 Introduction This study aimed at evaluating the impact of three different pre-transplant therapies on the outcome of patients (pts) eligible for high-dose therapy. Methods two-hundred sixty eight newly diagnosed MM pts aged £65 years, Durie-Salmon stage III, II, or I in progression, were consecutively enrolled from 2000 to 2007 in three different protocols, with three different pre-transplant therapy: Group 1: (145 pts) 3 pulse-VAD cycles; Group 2: (67 pts) 3 pulse-VAD cycles plus 3 Thal-Dex cycles (thalidomide at the dose of 100 mg/day orally at bedtime, continuously for 3 months, oral dexamethasone at the dose of 20 mg on days 1-4 and 14-17 every 28 days); Group 3: (57pts) 4 Vel-Dex courses (Bortezomib 1.3 mg/m2 i.v. on days 1, 4, 8, 11; oral Dexamethasone 40 mg on days 1-4 and 8-11 every 3 weeks). After induction all pts received two DCEP-short cycles as mobilization (oral Dexamethasone 40 mg/day on days 1-4 + Cyclophosphamide 700 mg/m2/day i.v., Etoposide 100 mg/ m2/day i.v., cisPlatin 25 mg/m2/day for 2 days) with peripheral blood stem-cell (PBSC) collection prompted by G-CSF followed by one or two transplants (Tx) with melphalan 200 mg/m2 as conditioning regimen. Response was defined according to IMWG uniform criteria. Pts were considered responsive when obtaining at least a PR. Results pts in the three group were similar for age, gender, Ig type, ISS stage. A significant higher percentage of Durie and Salmon stages III was found in group 3 (83% vs 68% in group 1 and 67% in group 2, p=0.0002). The median follow-up was 46 (1-150) months for group 1, 43 (1-68) months for group 2, and 29.7 (1-79) months for group 3. At the time of this analysis in the three groups 51%, 65%, 90% of transplanted pts respectively were still alive, and progression after transplant was registered in 84%, 80%, 50% respectively. Patient flow before Tx was similar (p=0.45): 19% in group 1, 27% in group 2, 23% in group 3. In group 1, 2% of pts went off-study after VAD, and 17% after mobilization phase. In group 2, patient flow was equally distributed: 7% after pulse VAD, 10% after thal-dex, 9% after DCEP. In group 3, 12% of the pts went off-study after Vel-Dex, 11% after DCEP. Table 1 summarized responses. In group 3 (Vel-Dex) response was better along all protocol phases with respect to group 1 or 2 (p<0.00001). The number of responsive pts progressively increased from 87% after Vel-Dex (CR 31%), to 96% after transplant (CR 38%). Response rates of group 1 and 2 patients were not significantly different either after induction (p=0.6), after DCEP (p=0.5), and after Tx (p=0.65). On intention to treat basis, vel-dex induction produced a better, although not significant, PFS (34.6 months vs 29 in group 1 and 26.8 in group 2, p=0.56). OS were not statistically different among the three groups, event though the different follow-up could affect the analysis (median OS 110 in group 1, 66 months in group 2, and not reached in group 3, p=0.37). In multivariate analysis PFS was improved only by the achievement of CR (p=0.001). No significant difference was observed between VGPR or PR (p=0.43). Conclusion In this study, only CR not VGPR impacts on the outcome. Vel-Dex producing a significant high CR rate after TX (38%), seems to improve survival of MM patients candidate to high-dose therapy with respect to conventional pre-transplant strategies. Disclosures Morra: Roche:.

Retrospective Comparison of Transplant Outcomes in Patients with Multiple Myeloma According to Induction Therapy with Thalidomide/Dexamethasone (TD) with or without Bortezomib (VTD).

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 948-948 ◽  
Author(s):  
Sergio Giralt ◽  
Rupi Thandi ◽  
Muzaffar Qazilbash ◽  
Floralyn Mendoza ◽  
Eric Han ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Induction Therapy ◽  
Response Rates ◽  
Induction Treatment ◽  
High Dose ◽  
Cell Transplant ◽  
High Dose Therapy ◽  
Dose Therapy ◽  
Treatment Characteristics ◽  
The Impact

Abstract Background: Thalidomide/Dexamethasone (TD) has become one of the most commonly used induction therapies for patients with symptomatic multiple myeloma (MM) eligible for high dose therapy (HDT) intensification with autologous stem cell transplant (ASCT). Bortezomib (Velcade) has been added to the combination of TD (VTD) in an effort to reduce MM tumor burden further prior to HDT.The impact of this addition on HDT outcomes has not been fully explored. Purpose: To determine the impact of the addition of bortezomib to TD induction therapy in patients with MM undergoing HDT and ASCT consolidation. Patients and Methods: Patients were eligible for this analysis if they had undergone HDT with ASCT for first remission consolidation or primary refractory disease within 12 months of diagnosis between 9/03 and 12/05 and had received either TD or VTD as induction therapy. Patients receiving VTD after TD were excluded. Patients receiving more than 1 chemo regimen other than TD or VTD were excluded. Chemomobilization was NOT considered an exclusion criteria. Results A total of 78 patients qualified for the analysis (27 VTD; 51 TD). Patient and treatment characteristics are summarized in table 1. In brief, the patients receiving VTD had a higher rate of cytogenetic abnormalities and received less cycles of chemotherapy prior to SCT. Although pre-SCT response rates were similar between patients receiving VTD or TD (95% vs 92%) there was a trend for a higher CR rate in the VTD group (15% vs 6%). Post transplants response rates assessed between 3–6 months demonstrated that 28% and 38% of VTD patients achieved near CR and CR respectively while 19% and 23% had these responses post TD induction. There was no difference in 2 year OS and PFS among patients receiving VTD or TD (91% vs 81% and 35% and 56% respectively). Conclusion: Both VTD and TD as induction treatment are associated with high response rates prior to SCT as well as 6 months post SCT. In this retrospective analysis no survival benefit was seen for induction therapy with VTD over TD, despite higher near CR and CR rates. However randomized trials need to be performed addressing type of induction as well as duration of induction therapy prior to high dose therapy consolidation. Patient and Treatment Characteristics Variables VTD TD N 27 51 Median Age 54 (34–71) 56 (34–71) %ISS> 1 76% 65% % CG Abnormal 37% 19% p=.009 B2M @ Dx 2.99 3.19 Cycles Prior to SCT 2 4 p=.00009 % Mel 200 74% 69% Post SCT Maintenance 15/27 23/51

scholarly journals Adverse Cytogenetics, with or without Trisomies, in Patients Undergoing High Dose Therapy for Multiple Myeloma and Impact of Post-Transplant Maintenance Therapy

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3456-3456
Author(s):  
Gregory P Kaufman ◽  
Morie A Gertz ◽  
Angela Dispenzieri ◽  
Martha Q Lacy ◽  
Francis K Buadi ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Maintenance Therapy ◽  
Research Funding ◽  
Single Agent ◽  
Prognostic Significance ◽  
Common Mechanism ◽  
High Dose ◽  
High Dose Therapy ◽  
Dose Therapy ◽  
The Impact

Abstract Background FISH abnormalities including t(14;16), t(14;20), t(4;14) and the loss of P53 remain a common mechanism for classifying patients (pts) with newly diagnosed multiple myeloma (MM) as adverse risk. In contrast, trisomies in MM are associated with superior outcomes and may ameliorate the negative prognostic significance conferred by adverse FISH abnormalities. High dose therapy (HDT) consisting of high dose melphalan and autologous stem cell transplantation with consideration of maintenance therapy is a common treatment strategy for transplant eligible MM pts. However, there is limited information regarding the impact of various cytogenetic abnormalities, alone or in combination with trisomies, in the context of HDT, and the efficacy of maintenance approaches in the novel agent era. Aim To determine the clinical significance of FISH abnormalities in MM pts undergoing HDT and subsequent consideration of maintenance therapy in recent years. Methods We retrospectively examined a cohort of all pts with MM who underwent first HDT at Mayo Clinic Rochester between 2008 and 2012. Medical records were reviewed under IRB approval in accordance with the principals of the Helsinki declaration. FISH results were obtained from within 6 months of diagnosis (Dx), and if unavailable pts were excluded. Pts were considered for maintenance therapy following response assessment by their treating hematologist, typically around day 100 following HDT, and were categorized based on the intent of that discussion; length of maintenance and dose reductions were not evaluated. PFS and OS were calculated from date of transplant and OS was also estimated from Dx. Timing of HDT was restricted to within one year of MM Dx (early HDT). Results 300 pts had available FISH and underwent early HDT. Median age at dx was 60 (23-75), and median follow up from Dx was 40 months (7.5-90) with 229 (76%) alive at time of analysis. The median time to HDT from Dx was 5.8 months (95% CI 5.4-8.0). At the time of HDT 249 pts (83%) were in a partial response or better. Overall, 73 pts (24%) had adverse risk FISH from dx as described, 154 pts (51%) had at least one trisomy, and 32 pts (10.7%) had a concomitant adverse FISH abnormality and a trisomy. Of all pts, 112 (37%) received maintenance therapy of some sort, most commonly single agent lenalidomide (n=67 pts) or bortezomib (n=36). Of the 73 pts with adverse FISH, 54 (74%) received maintenance therapy following initial HDT compared with 58 of 227 pts (26%) with non-adverse FISH. Among pts with adverse FISH, median PFS and OS was 21 months (95% CI 16-24) and 57 months (95% CI 41-NR) respectively, compared with 24 months (95% CI 21-26) and not met respectively for pts with no adverse FISH (p =0.08 and p=0.04). The OS from Dx was 63 months (95% CI 46-NR) and not met, respectively for pts with adverse FISH and no adverse FISH (p=0.04). Among adverse FISH pts, PFS following initial HDT was improved with any maintenance therapy (23 months (95% CI 18-33) versus 13 months (95% CI 6-22), p=0.0016). OS was not statistically different among pts with adverse FISH whether or not they received maintenance therapy, both from date of HDT as well as from Dx. For pts with non-adverse FISH at Dx similar findings were observed, with an increase in PFS following HDT with any maintenance therapy (30 months (95% CI 23-48) versus 22 months (18-24)), without a difference in OS. Further analysis of the group of pts with adverse FISH status revealed the PFS benefit seen with maintenance therapy was greatest for a subgroup of pts with concomitant trisomies (29 months (95%CI 18-38) versus 14 months (95%CI 8-16) p=0.0003) as compared to pts with adverse FISH without concomitant trisomies (19 months (95%CI 13-35) versus 12 months (95% CI 3-24) p=0.204) (figure 1). However, OS either from HDT or Dx did not differ for pts with adverse FISH with or without concomitant trisomies regardless of maintenance status. Conclusions Our data support an improvement in PFS with maintenance therapy following initial HDT amongst adverse risk FISH MM pts, however no OS benefit was observed with maintenance therapy irrespective of FISH status. Among pts with adverse FISH, maintenance strategies improve PFS for pts with a concomitant trisomy. No PFS benefit was seen with maintenance therapy in pts without concomitant trisomies. Future trials of maintenance therapy post HDT should consider evaluating and reporting on the subgroup of adverse FISH pts with concomitant trisomies. Figure 1 Figure 1. Disclosures Kumar: Janssen: Consultancy, Research Funding; Array BioPharma: Consultancy, Research Funding; Sanofi-Aventis: Consultancy, Research Funding; Onyx Pharmaceuticals: Consultancy, Research Funding; Millennium: The Takeda Oncology Co.: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Skyline Diagnostics: Membership on an entity's Board of Directors or advisory committees.

The Impact of Histologic Grade on the Outcome of High-Dose Therapy and Autologous Stem Cell Transplantation for Follicular Lymphoma.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 679-679
Author(s):  
Rosalyn N. Pham ◽  
Ted A. Gooley ◽  
Grant E. Keeney ◽  
Oliver W. Press ◽  
John M. Pagel ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
B Cell Lymphoma ◽  
Histologic Grade ◽  
High Dose ◽  
High Dose Therapy ◽  
Dose Therapy ◽  
The Impact

Abstract Follicular lymphomas (FL) represent approximately one-fourth of all non-Hodgkins lymphomas (NHL) and are the most common indolent lymphomas. Studies suggest that patients (pts) with relapsed FL treated with high-dose therapy (HDT) and autologous stem cell transplantation (ASCT) have prolonged progression-free survival (PFS) and overall survival (OS) as compared to those treated with standard chemotherapy alone, yet the impact of histologic grade on these outcomes has not been established. In order to address this issue, we evaluated all FL pts that underwent HDT and ASCT at our center from Dec 1985 to June 2005 (n=219). Pts with transformation to diffuse large B-cell lymphoma were excluded. Histologic grades 1, 2, and 3 were present in 106 (48%), 75 (34%), and 38 (17%) pts, respectively. Other baseline characteristics at the time of transplant for this cohort included: Female = 39%, median age = 48 (range 24 – 66), stage III/IV = 93%, elevated LDH = 27%, median number of prior regimens = 3 (range 1 to 11), prior radiation therapy (RT) = 16%, bulk ≥5cm = 19%, chemosensitive = 68%, complete remission = 18%. 53% of pts are alive and 36% are alive without relapse at last contact leading to 5- and 10-year estimates of 60% and 42% for OS and 39% and 28% for PFS, respectively. The median follow-up for surviving patients was 7.8 years. The 5- and 10-year OS estimates for the histologic grades were grade 1: 57% and 42%, 2: 60% and 36%, and 3: 65% and 55% (Figure). Five- and 10-year PFS estimates were grade 1: 35% and 27%, grade 2: 44% and 25%, and grade 3: 45% and 40% (Figure). In order to adjust for any potential imbalances of critical prognostic factors between the three grades, we performed a multivariable analysis adjusting for criteria that were found to be associated with OS and/or PFS (age, # of prior regimens, prior RT, chemosensitivity, and LDH) and obtained the hazard ratios (HR) and p-values noted (Table). These data suggest that 1) prolonged OS and PFS can be attained via HDT and ASCT in FL pts, 2) histologic grade does not statistically significantly impact outcomes, and 3) other factors noted above should be utilized to predict outcome and counsel patients. Grade HR for Death (95% CI) p HR for Death or Progression (95% CI) p 1 1 (– –) – 1 (– –) – 2 1.00 (0.66–1.54) 0.98 0.92 (0.63–1.34) 0.69 3 0.66 (0.35–1.24) 0.20 0.79 (0.48–1.33) 0.38 Figure Figure

The impact of HBO on early ALC recovery following high-dose therapy and autologous transplantation.

2015 ◽  
Vol 33 (15_suppl) ◽  
pp. 7034-7034
Author(s):  
Omar Salah Aljitawi ◽  
Mary Markiewicz ◽  
Amara Seng ◽  
Tara L. Lin ◽  
Siddhartha Ganguly ◽  
...  
Keyword(s):  
Autologous Transplantation ◽  
High Dose ◽  
High Dose Therapy ◽  
Dose Therapy ◽  
The Impact

Maintenance Treatment with Thalidomide after Autologous Transplantation for Myeloma : First Analysis of a Prospective Randomized Study of the Intergroupe Francophone du Myelome (IFM 99 02).

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 535-535 ◽  
Author(s):  
Michel Attal ◽  
Jean-Luc Harousseau ◽  
Serge Leyvraz ◽  
Chantal Doyen ◽  
Cyrille Hulin ◽  
...  
Keyword(s):  
Maintenance Treatment ◽  
High Dose ◽  
High Dose Therapy ◽  
Free Survival ◽  
Chromosome 13 ◽  
Dose Therapy ◽  
Autologous Transplant ◽  
Beta 2 ◽  
The Impact ◽  
To Receive

Abstract High dose therapy (HDT) supported with autologous stem cell transplantation has been introduced in the management of aggressive myeloma. However, after single or tandem transplantation, almost all patients ultimately relapse. New strategies are required to control any residual disease after HDT. The Intergroupe Francophone du Myelome (IFM) initiated a trial designed to evaluate the impact of maintenance treatment with Thalidomide on the duration of response after HDT. From April 2000 to October 2003, 1004 myeloma patients at diagnosis under the age of 65 years were enrolled in the IFM 99 protocol. 780 of them, without or with only one adverse prognostic factor (beta-2 microglobuline >3 mg/l or deletion of chromosome 13), were enrolled in the IFM 99 02 protocol. They were to receive the following treatment: 1) 3–4 cycles of the VAD regimen; 2) a first autologous transplant prepared with Melphalan 140 mg/m2; 3) a second autologous transplant prepared with Melphalan 200 mg/m2. Patients without progressive disease 2 months after the second transplant were randomized to receive: no maintenance treatment (arm A), maintenance treatment with Pamidronate (arm B) or maintenance treatment with Thalidomide and Pamidronate (arm C). As of May 2004, 580 patients (74%) have been randomized: 195 in arm A, 190 in arm B and 195 in arm C. Clinical characteristics of each group were similar. The median follow-up from diagnosis was 26 months (range: 6–50) Thalidomide was found to improve the Progression-free survival (PFS; p<0.007) and the Event-free-survival (EFS; p<0.01). Indeed, the 40-months post-diagnosis probability of PFS was 70% (95% CI= 42–80) in the Thalidomide arm versus 53% (95% CI= 37–65) in arm A, and 52% (95% CI= 36–68) in arm B. Most patients (60%) enrolled in arm A and B received Thalidomide at time of relapse. The overall survival was similar in the 3 treatment groups. Among the 580 randomized patients, 2 factors were found to be associated with a longer EFS : low beta-2-microglobulin at diagnosis (p<0.01) and treatment arm (p<0.01). Deletion of chromosome 13 (FISH analysis) was not related to EFS. In conclusion, the first analysis of the IFM9902 trial strongly suggests that Thalidomide is an effective maintenance treatment after high dose therapy for myeloma. The next analysis (November 2004) will be presented during the meeting.

Polymorphic variation in GSTP1 modulates outcome following therapy for multiple myeloma

Blood ◽  
2003 ◽  
Vol 102 (7) ◽  
pp. 2345-2350 ◽  
Author(s):  
Ranjit K. Dasgupta ◽  
Peter J. Adamson ◽  
Faith E. Davies ◽  
Sara Rollinson ◽  
Philippa L. Roddam ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Standard Dose ◽  
Progression Free Survival ◽  
Chemotherapeutic Agents ◽  
High Dose ◽  
Glutathione S Transferase ◽  
High Dose Therapy ◽  
Free Survival ◽  
Dose Therapy ◽  
The Impact

Abstract Glutathione S-transferase P1 (GSTP1) is a phase 2 drug metabolism enzyme involved in the metabolism and detoxification of a range of chemotherapeutic agents. A single nucleotide polymorphism (Ile105Val) results in a variant enzyme with lower thermal stability and altered catalytic activity. We hypothesized that patients with the less stable variant have a decreased ability to detoxify chemotherapeutic substrates, including melphalan, and have an altered outcome following treatment for multiple myeloma. We have assessed the impact of GSTP1 codon 105 polymorphisms in 222 patients entered into the Medical Research Council (MRC) myeloma VII trial (comparing standard-dose chemotherapy with high-dose therapy). In the standard-dose arm, patients with the variant allele (105Val) had an improved progression-free survival (PFS) (adjusted hazard ratios for PFS were 0.55 for heterozygotes and 0.52 for 105Val homozygotes, compared with 105Ile homozygotes; P for trend = .04); this was supported by a trend to improved overall survival, greater likelihood of entering plateau and shorter time to reach plateau in patients with the 105Val allele. No difference in outcome by genotype was found for patients treated with high-dose therapy. However, the progression-free survival advantage of the high-dose arm was seen only in patients homozygous for 105Ile (P = .008). (Blood. 2003;102:2345-2350)

Prolonged Remission Duration with Interferon Maintenance After Rituximab-Containing Induction in First-Line Advanced Stage Lymphoplasmacytic Lymphoma – a Retrospective Analysis of the German Low-Grade Lymphoma Study Group (GLSG)

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1639-1639
Author(s):  
Eva Hoster ◽  
Michael Unterhalt ◽  
Bernd Metzner ◽  
Michael Pfreundschuh ◽  
Peter Staib ◽  
...  
Keyword(s):  
Retrospective Analysis ◽  
Board Of Directors ◽  
Research Funding ◽  
High Dose ◽  
Lymphoplasmacytic Lymphoma ◽  
First Line ◽  
High Dose Therapy ◽  
Advisory Committees ◽  
Dose Therapy ◽  
The Impact

Abstract Abstract 1639 Introduction: Maintenance using interferon-α (IFN) had previously been shown to be effective in indolent lymphoma (Solal-Celigny et al., NEJM 1993, Hagenbeek et al., JCO 1998). However, data on the impact of IFN in lymphoplasmacytic lymphoma (LPL) and after immuno-chemotherapy are rare. In two GLSG first-line trials which included LPL patients, IFN-maintenance was intended in all patients responding to induction therapy and not assigned to high-dose therapy. We performed a retrospective analysis to compare the clinical outcome in LPL patients who received IFN-maintenance versus no consolidation or maintenance. We adjusted for potential confounders that might have influenced the decision not to start IFN-maintenance. Methods: In the GLSG first-line trials “CHOP vs. MCP” and “CHOP vs. R-CHOP” patients younger than 60 years had been randomized between consolidating high-dose radio-chemotherapy followed by autologous stem cell transplantation (ASCT) and IFN-maintenance. IFN-maintenance was also intended in all responding patients older than 60 years. Patients with LPL achieving a partial or complete remission after MCP, CHOP, or R-CHOP and who did not start ASCT were included in the current analysis. We compared patients in which IFN-maintenance was not started to patients with IFN-maintenance. We investigated patient and treatment characteristics of these groups in order to detect possible reasons why IFN-maintenance was not started. Outcome parameters were remission duration (RD) and overall survival (OS). RD, calculated from the end of induction to relapse or death, was censored at the latest follow-up date in patients without event, but also when a new antilymphoma therapy was initiated without any sign of progression. No censoring was done for any form of dose reduction or stopping of IFN, which was recommended in the trials if inacceptable side effects were observed. RD and OS were analysed by Kaplan-Meier curves and log rank test and we adjusted for potential confounders in multiple Cox-Regression. In order to assess the impact of IFN-maintenance after R-containing induction, we performed a subgroup analysis of R-CHOP treated patients. Results: IFN-maintenance was started in 56 (75%) of 75 responding LPL patients not treated with high-dose therapy. Patients with IFN-maintenance were younger (60 vs. 69 years, p=0.001), but other baseline characteristics (ECOG performance status, haemoglobin, LDH, platelets, β2-microglobulin, IgM) were comparable, as well as the percentage of patients with R-CHOP induction (64% vs. 63%). More patients treated with IFN had achieved a CR (18% vs. 0%). Patients with IFN-maintenance had significantly longer RD (hazard ratio, HR, 0.27, 95% CI 0.12 to 0.59, p=0.001) and OS (HR 0.19, 95% CI, 0.06 to 0.58, p=0.004) which was similarly seen after adjustment for age (RD: 0.32, 95% CI 0.14 to 0.78, p=0.012, OS: 0.30, 95% CI 0.08 to 1.04, p=0.058), or the achievement of a CR. Of 48 patients responding to R-CHOP, IFN-maintenance was started in 36 (75%). RD after 3 years was 87% vs. 41% (p<0.001) and the HR for IFN adjusted for age were 0.19 for RD (95% CI 0.06 to 0.66 p=0.009) and 0.21 for OS (95% CI 0.04 to 1.05, p=0.058). Conclusions: Although this is a non-randomized comparison based on a relatively small patient number, our results suggest that IFN-maintenance is effective in LPL also in the era of immuno-chemotherapy. It seems relevant to keep in mind that interferon-a may be a therapeutic option when other strategies are not possible. It may also be relevant for future investigations in lymphoma therapy. Disclosures: Hoster: Roche: Honoraria. Off Label Use: Interferon-alpha in lymphoplasmacytic lymphoma. Pfreundschuh:Roche: Membership on an entity's Board of Directors or advisory committees, Research Funding. Dreyling:Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Hiddemann:Roche: Research Funding.

scholarly journals Frontline therapy of multiple myeloma

Blood ◽  
2015 ◽  
Vol 125 (20) ◽  
pp. 3076-3084 ◽  
Author(s):  
Philippe Moreau ◽  
Michel Attal ◽  
Thierry Facon
Keyword(s):  
Multiple Myeloma ◽  
Progression Free Survival ◽  
High Dose ◽  
Newly Diagnosed ◽  
Therapeutic Approaches ◽  
Time To Progression ◽  
High Dose Therapy ◽  
Free Survival ◽  
The Past ◽  
Frontline Treatment

Abstract In the past decade, one of the major advances in the management of patients with symptomatic newly diagnosed multiple myeloma has been the introduction of novel agents, thalidomide, bortezomib, and lenalidomide, as part of frontline treatment in both transplant and nontransplant candidates. These drugs have markedly improved the rate of complete remission, and time to progression, progression-free survival, and overall survival have significantly increased. This article focuses on more recent frontline therapeutic approaches both in older patients, not eligible for high-dose therapy and autologous stem cell transplantation (ASCT), and in younger patients eligible for early ASCT.

Sign in / Sign up

Export Citation Format

Share Document