scholarly journals Individualized Screening Trial of Innovative Glioblastoma Therapy (INSIGhT): A Bayesian Adaptive Platform Trial to Develop Precision Medicines for Patients With Glioblastoma

2019 ◽  
pp. 1-13 ◽  
Author(s):  
Brian M. Alexander ◽  
Lorenzo Trippa ◽  
Sarah Gaffey ◽  
Isabel C. Arrillaga-Romany ◽  
Eudocia Q. Lee ◽  
...  
Keyword(s):  
Overall Survival ◽  
Biomarker Discovery ◽  
Progression Free Survival ◽  
Newly Diagnosed ◽  
Free Survival ◽  
Common Control ◽  
Low Probability ◽  
Trial Structure ◽  
Screening Trial ◽  
R132h Mutation

PURPOSE Adequately prioritizing the numerous therapies and biomarkers available in late-stage testing for patients with glioblastoma (GBM) requires an efficient clinical testing platform. We developed and implemented INSIGhT (Individualized Screening Trial of Innovative Glioblastoma Therapy) as a novel adaptive platform trial (APT) to develop precision medicine approaches in GBM. METHODS INSIGhT compares experimental arms with a common control of standard concurrent temozolomide and radiation therapy followed by adjuvant temozolomide. The primary end point is overall survival. Patients with newly diagnosed unmethylated GBM who are IDH R132H mutation negative and with genomic data available for biomarker grouping are eligible. At the initiation of INSIGhT, three experimental arms (neratinib, abemaciclib, and CC-115), each with a proposed genomic biomarker, are tested simultaneously. Initial randomization is equal across arms. As the trial progresses, randomization probabilities adapt on the basis of accumulating results using Bayesian estimation of the biomarker-specific probability of treatment impact on progression-free survival. Treatment arms may drop because of low probability of treatment impact on overall survival, and new arms may be added. Detailed information on the statistical model and randomization algorithm is provided to stimulate discussion on trial design choices more generally and provide an example for other investigators developing APTs. CONCLUSION INSIGhT (NCT02977780) is an ongoing novel biomarker-based, Bayesian APT for patients with newly diagnosed unmethylated GBM. Our goal is to dramatically shorten trial execution timelines while increasing scientific power of results and biomarker discovery using adaptive randomization. We anticipate that trial execution efficiency will also be improved by using the APT format, which allows for the collaborative addition of new experimental arms while retaining the overall trial structure.

Individualized screening trial of innovative glioblastoma therapy (INSIGhT).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. TPS2079-TPS2079 ◽  
Author(s):  
Brian Michael Alexander ◽  
Lorenzo Trippa ◽  
Sarah C. Gaffey ◽  
Isabel Arrillaga ◽  
Eudocia Quant Lee ◽  
...  
Keyword(s):  
Pik3ca Mutation ◽  
Predictive Biomarkers ◽  
Progression Free Survival ◽  
Newly Diagnosed ◽  
Free Survival ◽  
Egfr Amplification ◽  
Common Control ◽  
Whole Exome ◽  
Screening Trial ◽  
Clinical Trial Information

TPS2079 Background: Patient with glioblastoma (GBM) with unmethylated MGMT promoters derive limited benefit from temozolomide (TMZ) and have dismal outcome. Prioritizing the numerous available therapies and biomarkers for late stage testing requires an efficient clinical testing platform. INSIGhT (NCT02977780) is a biomarker-based, Bayesian adaptively randomized, multi-arm phase II platform screening trial for patients with newly diagnosed GBM and unmethylated MGMT promoters. Methods: INSIGhT compares experimental arms to a common control of standard concurrent TMZ and radiation therapy (RT) followed by adjuvant TMZ. The primary endpoint is overall survival (OS). Patients with newly diagnosed, unmethylated GBM that are IDH R132H mutation negative, and with genomic data available or who consent to whole exome sequencing through the ALLELE companion study for biomarker grouping are eligible. Two experimental arms consist of concurrent RT/TMZ followed by adjuvant neratinib (EGFR, HER2, and HER4 inhibitor) or abemaciclib CDK 4/6 inhibitor), respectively, in place of TMZ. The other experimental arm is CC-115 (TORC1/2 and DNA PK inhibitor), which replaces TMZ in both the concurrent and adjuvant phases. Biomarker groups include: EGFR + patients with EGFR amplification/mutation; PI3K + patients with PIK3CA mutation/amplification, PIK3R1 mutation, AKT3amplification, PIK3C2B > 1 copy gain, or PTEN dual loss; CDK: + patients with wild-type RB1 and CDK4 amplification, CDK6 amplification, or CDKN2A > 1 copy loss. Given the lack of pretrial biomarker data and the anticipated overlap of the groups, randomization will initially be equal. As the trial progresses, randomization probabilities will be adapted based on the Bayesian estimation of the probability of treatment impact on progression-free survival (PFS). These randomization probabilities can vary among the biomarker groups so predictive biomarkers will be identified and utilized if present. Treatment arms may drop due to low probability of treatment impact on OS, and new arms may be added. Experimental arms are compared only with control and should be thought of as discrete experimental questions, with INSIGhT being open to new investigators with proposed therapeutic hypotheses. Clinical trial information: NCT02977780.

scholarly journals Subcutaneous Administration of Bortezomib in Combination with Thalidomide and Dexamethasone for Treatment of Newly Diagnosed Multiple Myeloma Patients

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Shenghao Wu ◽  
Cuiping Zheng ◽  
Songyan Chen ◽  
Xiaoping Cai ◽  
Yuejian Shi ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Adverse Events ◽  
Subcutaneous Administration ◽  
Progression Free Survival ◽  
The Other ◽  
Newly Diagnosed ◽  
Efficacy And Safety ◽  
Free Survival ◽  
Grade 3

Objective. To investigate the efficacy and safety of the treatment of the newly diagnosed multiple myeloma (MM) patients with the therapy of subcutaneous (subQ) administration of bortezomib and dexamethasone plus thalidomide (VTD) regimen.Methods. A total of 60 newly diagnosed MM patients were analyzed. 30 patients received improved VTD regimen (improved VTD group) with the subQ injection of bortezomib and the other 30 patients received conventional VTD regimen (VTD group).The efficacy and safety of two groups were analyzed retrospectively.Results. The overall remission (OR) after eight cycles of treatment was 73.3% in the VTD group and 76.7% in the improved VTD group (P>0.05). No significant differences in time to 1-year estimate of overall survival (72% versus 75%,P=0.848) and progression-free survival (median 22 months versus 25 months;P=0.725) between two groups. The main toxicities related to therapy were leukopenia, neutropenia, thrombocytopenia, asthenia, fatigue, and renal and urinary disorders. Grade 3 and higher adverse events were significantly less common in the improved VTD group (50%) than VTD group (80%,P=0.015).Conclusions. The improved VTD regimen by changing bortezomib from intravenous administration to subcutaneous injection has noninferior efficacy to standard VTD regimen, with an improved safety profile and reduced adverse events.

Prognostic Value of Syndecan-1 in Multiple Myeloma and its Relationship with Other Prognostic Factors.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2402-2402 ◽  
Author(s):  
Shaji Kumar ◽  
Emily Blood ◽  
Martin M. Oken ◽  
Philip R. Greipp
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Prognostic Factors ◽  
Bone Disease ◽  
Prognostic Value ◽  
Progression Free Survival ◽  
Type I ◽  
Newly Diagnosed ◽  
Clinical Markers ◽  
Free Survival

Abstract Background: Syndecan-1 (CD138) is a heparan sulfate bearing proteoglycan found on various epithelial cells as well as on B lineage cells depending on its stage of development. Syndecan-1 (CD138) is abundantly expressed by plasma cells, especially myeloma cells. The extra cellular domain along with the heparan sulfate side chains can be cleaved off the cell surface and can be detected in the serum as soluble syndecan. Syndecan possibly plays a multifunctional role in the biology of myeloma. It has been shown to be an independent prognostic factor in patients with multiple myeloma. It has also been shown to promote myeloma cell growth through different mechanisms. Its expression has also been suggested to correlate with bone disease in MM. Methods: In this study we studied serum levels of soluble syndecan in newly diagnosed MM patients enrolled in the Eastern Cooperative Oncology Group (ECOG) E9486 and its associated correlative laboratory clinical trial E9487. We evaluated the prognostic value of syndecan in MM and its relationship to other known prognostic factors for this disease. In addition, syndecan levels were correlated with clinical and laboratory markers of bone disease. Results: A total of 501 patients were studied and the median serum syndecan-1 was 158 ng/mL. Syndecan levels correlated positively with other prognostic factors and markers of tumor burden such as β2-microglobulin (correlation coefficient 0.3; P <0.00001), labeling index (0.25; <0.0001), creatinine (0.23; <0.0001), soluble IL6 receptor (0.3; <0.0001), BM plasma cell percentage (0.16; <0.0006), and disease stage (P=0.0007). Significant differences in the overall and progression free survival was found between two groups of patient separated using the median value as cut-off. The High syndecan group had a median overall survival of 36.3 months compared to 49.3 months for the low syndecan group (P < 0.0001). Similarly, the high syndecan group had progression free survival of 25.4 months compared to 33.5 months for the low syndecan group (P < 0.0001). In a proportional hazards model including syndecan-1 as well as labeling index, β2M, Platelet count, IL-6R, syndecan-1 retained its prognostic value for overall survival (HR 1.3, P = 0.021). Syndecan levels were correlated with various bone markers including C-terminal telopeptide of type I collagen (ICTP), osteocalcin (OC), C-terminal type I procollagen (PICP), bone-specific alkaline phosphatase (BAP), and tartrate resistant alkaline phosphatase (TRAP) and were found to correlate only with ICTP (0.25, P < 0.0001). No correlation was found between clinical markers of bone disease including presence of lytic lesions, osteoporosis and pathologic fractures on X-rays or bone pain. Conclusion: In this large study, we once again confirm the prognostic value of serum syndecan-1 levels in large group of patients with newly diagnosed myeloma. Syndecan-1 level correlates with other disease markers. Syndecan levels also correlated with ICTP, a marker of bone turnover, though no strong correlation was found between syndecan levels and clinical markers of myeloma bone disease. The biological basis of these finding needs further evaluation.

Bevacizumab plus radiotherapy for elderly patients with glioblastoma (ARTE).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. TPS2105-TPS2105 ◽  
Author(s):  
Ghazaleh Tabatabai ◽  
Michael Weller
Keyword(s):  
Overall Survival ◽  
Elderly Patients ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Combined Modality Treatment ◽  
Newly Diagnosed ◽  
Free Survival ◽  
Biomarker Analysis ◽  
Radiotherapy Alone ◽  
Temozolomide Chemotherapy

TPS2105 Background: The standard of care for patients with newly diagnosed glioblastomas after surgical resection is radiotherapy with concomitant and adjuvant temozolomide chemotherapy. Yet, inclusion into the pivotal trial was limited to patients up to the age of 70, and subgroup analyses suggested that older patients did not gain benefit from combined modality treatment. Further, the efficacy of radiotherapy has been confirmed in a randomized trial comparing best supportive care versus radiotherapy alone. Of note, hypofractionated radiotherapy is equieffective in patients aged 65-70 years and more. Two randomized trials in elderly patients (NOA-08, Nordic Trial) indicated smilar efficacy of primary temozolomide chemotherapy alone compared with radiotherapy alone. Combined radiochemotherapy is compared with radiotherapy alone in an ongoing NCIC-CTG EORTC TROG Japanese group trial 26062-22061. Thus, radiotherapy alone is the standard of care for newly diagnosed glioblastoma of elderly patients. These clinical data justify the exploration of new, temozolomide-free first-line treatment strategies in elderly patients. Methods: The ARTE trial will therefore investigate bevacizumab when added to a short course of radiotherapy and bevacizumab maintenance therapy until progression. The translational research program shall include blood and urine biomarker analysis and FET-PET in addition to MRI for monitoring the course of the disease. This trial is an explorative randomized, non-comparative phase II trial aiming at recruiting 60 patients in Switzerland. Elderly patients (> 65) will be randomized 2:1 either to the experimental arm (bevacizumab plus radiotherapy) or the standard arm (radiotherapy). The primary endpoint is median overall survival. Secondary endpoints include overall survival at 6 months, overall survival at 12 months, median progression-free survival, progression-free survival at 6 months, median time to treatment failure.

Final results of a single-arm phase II study of bevacizumab and temozolomide following radiochemotherapy in newly dignosed adult glioblastoma patients.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 2076-2076 ◽  
Author(s):  
Martin Kelly Nicholas ◽  
Rimas Vincas Lukas ◽  
Christine Amidei ◽  
Nicholas Vick ◽  
Nina Paleologos ◽  
...  
Keyword(s):  
Overall Survival ◽  
Radiation Treatment ◽  
Treatment Phase ◽  
Progression Free Survival ◽  
Concomitant Administration ◽  
Newly Diagnosed ◽  
Free Survival ◽  
Intention To Treat ◽  
Newly Diagnosed Glioblastoma ◽  
Post Radiation

2076 Background: This study evaluated efficacy and safety of bevacizumab (BEV) added to the post-radiation treatment phase for patients with newly diagnosed glioblastoma (GBM). Methods: Sixty-two participants with newly diagnosed GBM were enrolled between May 2007 and June 2010. Participants received standard radiation therapy (RT) within 6 weeks of surgery, and concomitant administration of temozolomide (TMZ). Four weeks after radiation, treatment with TMZ (Days 1-5 of a 28 day cycle) with BEV, (days 1 and 15 of a 28 day cycle) was started, and continued until disease progressed or adverse effects indicated need to stop treatment. Analyses were completed for all participants by intention to treat (ITT), with progression-free survival (PFS) and overall survival (OS) serving as primary and secondary endpoints respectively. Results: Subbjects completed a mean of 7.7 (range 0-29) cycles of post-RT with BEV and TMZ. Twenty participants (32%) were unable to proceed to the post-RT phase. The forty-two participants who did proceed to the post-RT phase completed a mean of 11.5 cycles of treatment. Thirty-eight participants (61%) stopped the study due to disease progression; 6 participants (14%) voluntarily discontinued treatment after 24 cycles with at least stable disease. At a median follow-up time of 24 months, median progression-free survival (PFS) for all participants was 8.8 months while median overall survival (OS) was 16.5 months for all participants. Ly with These results also compare favorably with recently reported results from the AVAglio study (PFS = 10.6 mo.). The toxicity profile was consistent with that reported in similar studies. MGMT promoter methtion.ylation status is under investiga Conclusions: Participants in this study demonstrated a median 1.9 month PFS benefit as compared to the 6.9 median OS reported by Stupp, et al. (2005) and a median 1.9 month OS benefit as compared to the 14.6 month median OS reported by Stupp, et al. (2005). Results suggest that the addition of bevacizumab to the post-RT phase of treatment improves both PFS and OS for persons with GBM despite the high percentage of participants being unable to progress to post-radiation treatment. Clinical trial information: NCT005906.

Adjuvant Procarbazine, Lomustine, and Vincristine Improves Progression-Free Survival but Not Overall Survival in Newly Diagnosed Anaplastic Oligodendrogliomas and Oligoastrocytomas: A Randomized European Organisation for Research and Treatment of Cancer Phase III Trial

2006 ◽  
Vol 24 (18) ◽  
pp. 2715-2722 ◽  
Author(s):  
Martin J. van den Bent ◽  
Antoine F. Carpentier ◽  
Alba A. Brandes ◽  
Marc Sanson ◽  
Martin J.B. Taphoorn ◽  
...  
Keyword(s):  
Overall Survival ◽  
Controlled Trial ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Newly Diagnosed ◽  
Free Survival ◽  
Oligodendroglial Tumors ◽  
Multicenter Randomized Controlled Trial ◽  
Genetic Subgroup ◽  
Pcv Chemotherapy

Purpose Anaplastic oligodendrogliomas are more responsive to chemotherapy than high-grade astrocytomas. We investigated, in a multicenter randomized controlled trial, whether adjuvant procarbazine, lomustine, and vincristine (PCV) chemotherapy improves overall survival (OS) in newly diagnosed patients with anaplastic oligodendrogliomas or anaplastic oligoastrocytomas. Patients and Methods The primary end point of the study was OS; secondary end points were progression-free survival (PFS) and toxicity. Patients were randomly assigned to either 59.4 Gy of radiotherapy (RT) in 33 fractions only or to the same RT followed by six cycles of standard PCV chemotherapy (RT/PCV). 1p and 19q deletions were assessed with fluorescent in situ hybridization. Results A total of 368 patients were included. The median follow-up time was 60 months, and 59% of patients have died. In the RT arm, 82% of patients with tumor progression received chemotherapy. In 38% of patients in the RT/PCV arm, adjuvant PCV was discontinued for toxicity. OS time after RT/PCV was 40.3 months compared with 30.6 months after RT only (P = .23). RT/PCV increased PFS time compared with RT only (23 v 13.2 months, respectively; P = .0018). Twenty-five percent of patients were diagnosed with combined 1p/19q loss; 74% of this subgroup was still alive after 60 months. RT/PCV did not improve survival in the subgroup of patients with 1p/19q loss. Conclusion Adjuvant PCV chemotherapy does not prolong OS but does increase PFS in anaplastic oligodendroglioma. Combined loss of 1p/19q identifies a favorable subgroup of oligodendroglial tumors. No genetic subgroup could be identified that benefited with respect to OS from adjuvant PCV.

RTOG 0131: Phase II trial of pre-irradiation and concurrent temozolomide in patients with newly diagnosed anaplastic oligodendrogliomas and mixed anaplastic oligodendrogliomas: Relationship between 1p/19q status and progression-free survival

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 1517-1517 ◽  
Author(s):  
M. A. Vogelbaum ◽  
B. Berkey ◽  
D. Peereboom ◽  
C. Giannini ◽  
R. Jenkins ◽  
...  
Keyword(s):  
Overall Survival ◽  
Radiation Therapy ◽  
Median Time ◽  
Phase Ii ◽  
Progression Free Survival ◽  
Chromosome 8 ◽  
Newly Diagnosed ◽  
Time To Progression ◽  
Durable Response ◽  
Free Survival

1517 Background: In a previous report, we showed in patients with newly diagnosed anaplastic oligodendrogliomas (AOs) and mixed anaplastic oligoastrocytomas (MAOs) that temozolomide (TMZ) can be given concurrently with radiation therapy (RT) with acceptable toxicity. We have now evaluated the efficacy of this regimen and correlated durability of response with tumor 1p/19q genotype. Methods: A phase II study was performed to evaluate the use of pre-RT TMZ followed by concurrent RT and TMZ in patients with newly diagnosed AO or MAO. The primary endpoint was to determine the pre-RT TMZ six-month progression rate, and secondary endpoints included progression-free survival and overall survival. Results: 40 eligible patients were entered into the trial. Thirty-two patients completed 6 months of pre-RT TMZ and concurrent RT and TMZ. Of the remaining eight patients, 4 withdrew due to toxicity and 4 other patients withdrew from study without evidence of toxicity or pre-RT progression. 1p/19q data are available in 37 cases; 23 tumors had loss of heterozygosity (LOH) of both 1p and 19q (double-deleted) while 14 tumors had LOH of either 1p or 19q (n = 3), or no LOH (n = 11). To date, 11 patients have experienced tumor progression; 1p/19q data are available for 10 of these cases (2 are double-deleted (2/23 = 9%), 8 have at least one intact chromosome (8/14 = 57%). Kaplan-Meier analysis demonstrates that progression free survival is significantly better for the double-deleted group (median time to progression not reached) than for the intact group (median time to progression = 15.2 months, p = 0.001). Overall survival is 98% (39/40) with a median follow-up of 17.5 months (2.8 - 31.1 months). Conclusions: LOH of both 1p and 19q is strongly correlated with a durable response of AO and MAO to a combined regimen of chemotherapy and radiation therapy. Tumors that are intact at 1p and/or 19q progress early despite an aggressive therapeutic regimen. These results suggest that future clinical trials should be prospectively stratified by tumor 1p/19q genotype. [Table: see text]

CTNI-40. EVALUATING FEASIBILITY AND EFFICIENCY OF PHASE II ADAPTIVE PLATFORM TRIAL DESIGNS BASED ON THE INDIVIDUALIZED SCREENING TRIAL OF INNOVATIVE GLIOBLASTOMA THERAPY (INSIGhT) EXPERIENCE

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi68-vi69
Author(s):  
Rifaquat Rahman ◽  
Lorenzo Trippa ◽  
Eudocia Quant Lee ◽  
Isabel Arrillaga-Romany ◽  
Mehdi Touat ◽  
...  
Keyword(s):  
Phase Ii ◽  
Progression Free Survival ◽  
The United States ◽  
Experimental Therapy ◽  
Newly Diagnosed ◽  
Adaptive Randomization ◽  
Common Control ◽  
The Status ◽  
Trial Efficiency ◽  
Screening Trial

Abstract BACKGROUND The Individualized Screening Trial of Innovative Glioblastoma Therapy (INSIGhT) is a phase II platform trial with Bayesian adaptive randomization and deep genomic profiling to more efficiently test experimental agents in newly diagnosed glioblastoma and to prioritize therapies for late-stage testing. METHODS In the ongoing INSIGhT trial, patients with newly diagnosed MGMT-unmethylated glioblastoma are randomized to the control arm or one of three experimental therapy arms (CC-115, abemaciclib, and neratinib). The control arm therapy is radiotherapy with concomitant and adjuvant temozolomide, and primary endpoint is overall survival. Randomization has been adapted based on Bayesian estimation of biomarker-specific probability of treatment impact on progression-free survival (PFS). All tumors undergo detailed molecular sequencing, and this is facilitated with the companion ALLELE protocol. To evaluate feasibility of this approach, we assessed the status of this ongoing trial. RESULTS Since INSIGhT was activated 4.3 years ago, it has expanded to include 12 sites across the United States. A total of 247 patients have been enrolled. Randomization probabilities have been repeatedly adjusted over time based upon early PFS results to alter the randomization ratio from standard 1:1:1:1 randomization. All three arms have completed accrual and efficacy estimates are available based upon comparison to the common control arm in context of relevant biomarkers. There are 87 patients alive and in follow-up, and there are ongoing plans to add additional arms to evaluate further treatments in the future. CONCLUSION The INSIGhT trial demonstrates that a multi-center Bayesian adaptive platform trial is a feasible and effective approach to help prioritize therapies and biomarkers for newly diagnosed GBM. The trial has maintained robust accrual, and the simultaneous testing of multiple agents, sharing a common control arm and adaptive randomization serve as features to increase trial efficiency relative to traditional clinical trial designs.

Analysis of Outcome after Autologous Stem Transplantation in Patients with Newly Diagnosed Myeloma: Comparison of Different Induction Regimens.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3079-3079 ◽  
Author(s):  
Shaji Kumar ◽  
Martha Q. Lacy ◽  
Angela Dispenzieri ◽  
Suzanne R. Hayman ◽  
S. Vincent Rajkumar ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Induction Therapy ◽  
Stem Cell Transplant ◽  
Single Agent ◽  
Progression Free Survival ◽  
Initial Therapy ◽  
Cell Transplant ◽  
Newly Diagnosed ◽  
Free Survival

Abstract Background: Autologous stem cell transplantation (SCT) improves survival in patients (pts) with multiple myeloma (MM). We have previously demonstrated that the degree of response at transplant does not impact on the outcome of transplant. However, newer induction regimens such as thalidomide and dexamethasone (Thal-Dex) result in higher response rates compared to previously used regimens such as single agent dexamethasone or vincristine, doxorubicin, and dexamethasone (VAD). We examined the outcome of SCT following three different induction therapies for newly diagnosed MM, namely VAD, single agent Dex, and Thal-Dex. Patients and Methods: 340 patients with MM who received their SCT within 12 mos of diagnosis (median 5.8, range 3–12) were studied. Patients receiving more than one induction therapy as well as those in whom thalidomide was added to dexamethasone for lack of response were excluded from the analysis. There were 105 pts in the VAD group, 140 in the Dex group and 95 in the Thal-Dex group. Responses were defined using standard criteria. Results: The study cohort consisted of 209 males (59%), with a median age of 57 years (range 30–76) at transplant. Baseline characteristics were similar in the 3 groups, except for lower age in the VAD group (median 55.8) compared to Dex (59.6) and Thal Dex (57.4) and shorter time to transplant in the Dex group (5.4 m) compared to VAD (6.4) and Thal Dex (5.9). Markers of disease activity pre-transplant, including B2M and marrow plasma cell percentage were higher in the Dex group compared to either VAD or Thal Dex. The proportion of patients with any response to induction therapy was lower in the Dex group compared to the other two. All pts in the Dex and the Thal-Dex groups received melphalan only conditioning compared to 70% in the VAD group, the rest receiving Melphalan/TBI. An objective response was achieved after SCT in 96%, 97%, and 98% of pts in the VAD, Dex and Thal-Dex groups respectively (P=0.8). A complete response to SCT was seen in 49% of patients in VAD group, 45% among those in the Dex group and 38% among those in the Thal Dex group (P=0.38). There was no difference in the median progression free survival after transplant (P=0.21) or overall survival from diagnosis (P=.34) between the three groups. The proportion free from progression at 2 years post transplant was 54%, 55% and 46% for Dex, VAD and Thal-Dex respectively. The proportion surviving at 4 years from diagnosis was 64%, 65.4% and 72% respectively for the three groups. Conclusion: We did not observe any difference in the response rates including complete responses to SCT in the three groups with nearly all pts in each group achieving a response. The progression free survival and overall survival appear to be comparable between the three groups. The results from initial therapy cannot be compared between the three regimens since the study population is restricted to patients reaching stem cell transplant. Within the limits of the study, there does not appear to be any long term impact of the initial therapy for the patients going onto an early stem cell transplant. Figure Figure

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