Long-term outcomes for low-grade intracranial ganglioglioma: 30-year experience from the Mayo Clinic

2012 ◽  
Vol 117 (5) ◽  
pp. 825-830 ◽  
Author(s):  
Julia J. Compton ◽  
Nadia N. Issa Laack ◽  
Laurence J. Eckel ◽  
David A. Schomas ◽  
Caterina Giannini ◽  
...  
Keyword(s):  
Overall Survival ◽  
Radiation Therapy ◽  
Mayo Clinic ◽  
Progression Free Survival ◽  
Low Grade ◽  
Term Survival ◽  
Free Survival

Object Gangliogliomas comprise less than 1% of all brain tumors and occur most often in children. Therefore, there are a limited number of patients and data involving the use or role of adjuvant therapy after subtotal resections (STRs) of gangliogliomas. The objective of this study was to examine and review the Mayo Clinic experience of 88 patients with gangliogliomas, their follow-up, risk of recurrence, and the role of radiation therapy after STR or only biopsy. Methods Eighty-eight patients with gangliogliomas diagnosed between 1970 and 2007 were reviewed. Data on clinical outcomes and therapy received were analyzed. The Kaplan-Meier method was used to estimate progression-free survival (PFS) and overall survival. Results The median age at diagnosis was 19 years. The median potential follow-up as of June 2008 was 142 months (range 9–416 months). Fifteen-year overall survival was 94%, median PFS was 5.6 years, with a 10-year PFS rate of 37%. Progression-free survival was dramatically affected by extent of initial resection (p < 0.0001). Conclusions This single-institution retrospective series of patients with gangliogliomas is unique given its large cohort size with a long follow-up duration, and confirms the excellent long-term survival rate in this group. The study also shows the importance of resection extent on likelihood of recurrence. Patients with gangliogliomas who undergo STR or biopsy alone have poor PFS. Radiation therapy may delay time to progression in patients with unresectable disease.

Long-term survival and toxicity in patients with progressive advanced neuroendocrine tumors treated with lutetium peptide radiolabelled radiotherapy: A Western Australian long-term follow-up study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16202-e16202
Author(s):  
Kim Robyn Kennedy ◽  
Phillip Claringbold ◽  
William Macdonald ◽  
Glenn Boardman ◽  
David Turner Ransom ◽  
...  
Keyword(s):  
Overall Survival ◽  
Neuroendocrine Tumours ◽  
Progression Free Survival ◽  
Somatostatin Analogue ◽  
Term Survival ◽  
Free Survival ◽  
Follow Up Study ◽  
Long Term Follow Up

e16202 Background: There are limited treatment options for advanced neuroendocrine tumours, and radiolabelled somatostatin analogues have shown favourable safety and efficacy over other existing treatments. Lutetium Octreotate has been shown to be the somatostatin analogue of choice in Peptide Radiolabelled Radiotherapy (PRRT) for advanced neuroendocrine tumours (NETs). Methods: We conducted a retrospective review of the long term safety and survival outcomes of 104 patients prospectively treated on the CLEMENT1, CLEMENT2, NETTLE, and NETT VALuE trials where patients with advanced progressive NETs were treated with Lutetium Octreotate PRRT in Perth, Western Australia. With a median follow-up time of 68 months, this is the longest follow-up study of advanced NETs treated with Lutetium PRRT in the literature to date. Results: Results showed comparable periods of disease stability as other studies, with median progression free survival of 43 months, and superior survival to other series, with a median survival of 71 months. There were patients who had very durable responses, with five year overall survival 61.5%, five year progression free survival 30.1%, 10 year overall survival 30.1%, and 10 year progression free survival of 29.3%, demonstrating Lu 177 can provide a very long duration of response in some patients. PRRT treatment was well tolerated with 1.9% of patients suffering long term renal impairment, and 1% with long term mild thrombocytopenia attributed to PRRT. Importantly, there was a higher rate of MDS and leukaemia in our series (6.7%), which is likely attributed to the longer period of follow-up with all except one case occurring 48 months after PRRT treatment, which is later than the median follow up in most other studies. Conclusions: Overall, this study showed that Lutetium PRRT remains an efficacious and well tolerated treatment in long term follow-up. For clinicians deciding on the timing of PRRT for individual patients the 6.7% long term risk of MDS/leukaemia needs to be balanced against the 29.3% PFS at 10 years. Clinical trial information: ACTRN12610000440022.

Cetuximab and chemotherapy in the treatment of patients with initially “nonresectable” colorectal (CRC) liver metastases: Long-term follow-up of the CELIM trial.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 3538-3538 ◽  
Author(s):  
Gunnar Folprecht ◽  
Thomas Gruenberger ◽  
Wolf Bechstein ◽  
Hans-Rudolf Raab ◽  
Juergen Weitz ◽  
...  
Keyword(s):  
Liver Metastases ◽  
Tumor Response ◽  
Progression Free Survival ◽  
R0 Resection ◽  
Term Survival ◽  
Free Survival ◽  
Long Term Follow Up ◽  
Clinical Trial Information

3538 Background: CRC liver metastases can be resected after downsizing with intensive chemotherapy schedules, with a strong correlation between the response and resection rates. Cetuximab plus chemotherapy has been shown to increase the rates of tumor response and resection of liver metastases. (Van Cutsem et al, JCO 2011). Methods: Patients (pts) with technically non-resectable and/or with > 4 liver metastases were randomized to treatment with FOLFOX/cetuximab (arm A) or FOLFIRI/cetuximab (arm B) and evaluated regarding resectability every 2 months. Resection was offered to all patients who became resectable during the study. K-ras and b-raf status were retrospectively evaluated. Data on tumor response and resection were reported earlier (Folprecht et al, Lancet Oncol 2010). Overall and progression free survival were analyzed in December 2012. Results: Between Dec 2004 and March 2008, 56 pts were randomized to arm A, 55 to arm B. For the current analysis, 109 pts were evaluable for overall survival (OS), and 106 patients for PFS. The median OS was 35.7 [95% CI: 27.2-44.2] months (arm A: 35.8 [28.1-43.6], arm B: 29.0 [16.0-41.9], HR 1.03 [0.66-1.61], p=0.9). The median PFS was 10.8 [9.3-12.2] months (Arm A: 11.2 [7.2-15.3], Arm B: 10.5 [8.9-12.2], HR 1.18 [0.79-1.74], p=0.4). Patients with R0 resection had a better OS (median: 53.9 [35.9-71.9] mo) than patients without R0 resection (27.3 [21.1-33.4] mo, p=0.002) and a better PFS (median 15.4 [11.4-19.5] and 8.9 [6.7-11.1] mo in R0 resected and not R0 resected pts, p<0.001). The 5 year survival in R0 resected patients is 46.2% [29.5-62.9%]. Conclusions: This study confirmed a favourable long term survival of patients with initially “nonresectable” CRC liver metastases treated in a multidisciplinary approach of neoadjuvant chemotherapy with cetuximab and subsequent metastasectomy in pts who became resectable. Clinical trial information: NCT00153998. [Table: see text]

Role of Extent of Resection in the Long-Term Outcome of Low-Grade Hemispheric Gliomas

2008 ◽  
Vol 26 (8) ◽  
pp. 1338-1345 ◽  
Author(s):  
Justin S. Smith ◽  
Edward F. Chang ◽  
Kathleen R. Lamborn ◽  
Susan M. Chang ◽  
Michael D. Prados ◽  
...  
Keyword(s):  
Tumor Volume ◽  
Progression Free Survival ◽  
Extent Of Resection ◽  
Malignant Progression ◽  
Low Grade ◽  
Karnofsky Performance Score ◽  
Long Term Outcome ◽  
Free Survival

Purpose The prognostic role of extent of resection (EOR) of low-grade gliomas (LGGs) is a major controversy. We designed a retrospective study to assess the influence of EOR on long-term outcomes of LGGs. Patients and Methods The study population (N = 216) included adults undergoing initial resection of hemispheric LGG. Region-of-interest analysis was performed to measure tumor volumes based on fluid-attenuated inversion-recovery (FLAIR) imaging. Results Median preoperative and postoperative tumor volumes and EOR were 36.6 cm3 (range, 0.7 to 246.1 cm3), 3.7 cm3 (range, 0 to 197.8 cm3) and 88.0% (range, 5% to 100%), respectively. There was no operative mortality. New postoperative deficits were noted in 36 patients (17%); however, all but four had complete recovery. There were 34 deaths (16%; median follow-up, 4.4 years). Progression and malignant progression were identified in 95 (44%) and 44 (20%) cases, respectively. Patients with at least 90% EOR had 5- and 8-year overall survival (OS) rates of 97% and 91%, respectively, whereas patients with less than 90% EOR had 5- and 8-year OS rates of 76% and 60%, respectively. After adjusting each measure of tumor burden for age, Karnofsky performance score (KPS), tumor location, and tumor subtype, OS was predicted by EOR (hazard ratio [HR] = 0.972; 95% CI, 0.960 to 0.983; P < .001), log preoperative tumor volume (HR = 4.442; 95% CI, 1.601 to 12.320; P = .004), and postoperative tumor volume (HR = 1.010; 95% CI, 1.001 to 1.019; P = .03), progression-free survival was predicted by log preoperative tumor volume (HR = 2.711; 95% CI, 1.590 to 4.623; P ≤ .001) and postoperative tumor volume (HR = 1.007; 95% CI, 1.001 to 1.014; P = .035), and malignant progression-free survival was predicted by EOR (HR = 0.983; 95% CI, 0.972 to 0.995; P = .005) and log preoperative tumor volume (HR = 3.826; 95% CI, 1.632 to 8.969; P = .002). Conclusion Improved outcome among adult patients with hemispheric LGG is predicted by greater EOR.

Low-grade gliomas of the cerebral hemispheres in children: an analysis of 71 cases

1995 ◽  
Vol 82 (4) ◽  
pp. 536-547 ◽  
Author(s):  
Ian F. Pollack ◽  
Diana Claassen ◽  
Qasim Al-Shboul ◽  
Janine E. Janosky ◽  
Melvin Deutsch
Keyword(s):  
Overall Survival ◽  
Univariate Analysis ◽  
Tumor Resection ◽  
Progression Free Survival ◽  
Low Grade ◽  
Free Survival ◽  
Content Type ◽  
Low Grade Gliomas ◽  
Fine Print

✓ Low-grade gliomas constitute the largest group of cerebral hemispheric tumors in the pediatric population. Although complete tumor resection is generally the goal in the management of these lesions, this can prove difficult to achieve because tumor margins may blend into the surrounding brain. This raises several important questions on the long-term behavior of the residual tumor and the role of adjuvant therapy in the management of these lesions. To examine these issues, the authors reviewed their experience in 71 children with low-grade cerebral hemispheric gliomas who were treated at their institution between 1956 and 1991 and assessed the relationship between clinical, radiographic, pathological, and treatment-related factors and outcome. Only seven patients in the series died, one from perioperative complications, five from progressive disease, and one (a child with neurofibromatosis) from a second neoplasm. For the 70 patients who survived the perioperative period, overall actuarial survivals at 5, 10, and 20 years were 95%, 93%, and 85%, respectively; progression-free status was maintained in 88%, 79%, and 76%, respectively. On univariate analysis, the factor that was most strongly associated with both overall and progression-free survival was the extent of tumor resection (p = 0.013 and p = 0.015, respectively). A relationship between extent of resection and progression-free survival was present both in patients with pilocytic astrocytomas (p = 0.041) and those with nonpilocytic tumors (p = 0.037). Histopathological diagnosis was also associated with overall survival on univariate analysis; poorer results were seen in the patients with nonpilocytic astrocytoma compared to those with other low-grade gliomas, such as pilocytic astrocytoma, mixed glioma, and oligodendroglioma (p = 0.021). The use of radiotherapy was not associated with a significant improvement in overall survival (p = 0.6). All three patients who ultimately developed histologically confirmed anaplastic changes in the vicinity of the original tumor had received prior radiotherapy, 20, 46, and 137 months, respectively, before the detection of malignant progression. In addition, children who received radiotherapy had a significantly higher incidence of late cognitive and endocrine dysfunction than the nonirradiated patients (p < 0.01 and 0.05, respectively). The authors conclude that children with low-grade gliomas of the cerebral hemispheres have an excellent overall prognosis. Complete tumor resection provides the best opportunity for long-term progression-free survival. However, even with incomplete tumor excision, long-term progression-free survival is common. The findings in this study do not support the routine use of postoperative radiotherapy after an initial incomplete tumor resection: although irradiation appears to increase the likelihood of long-term progression-free survival, overall survival is not improved significantly, and long-term morbidity may be increased.

scholarly journals Clinical Outcome After Microsurgical Resection of Central Neurocytoma: A Single-Centre Analysis of 15 Years

2021 ◽  
Vol 12 ◽  
Author(s):  
Dan Cao ◽  
Yong Chen ◽  
Zhengqian Guo ◽  
Yibo Ou ◽  
Jian Chen
Keyword(s):  
Overall Survival ◽  
Progression Free Survival ◽  
Extent Of Resection ◽  
Central Neurocytoma ◽  
Complication Rates ◽  
Long Term Outcome ◽  
Free Survival ◽  
Risk Of Death

Objective: This study aimed to explore the immediate postoperative and long-term outcomes of central neurocytoma (CN) based on 15 years of experience in our institution.Methods: This single-institution study collected data of 43 patients with CN who underwent surgery between 2005 and 2020. We reviewed data of clinical, immediate postoperative outcome, and long-term outcome of patients. More specifically, we divided complications into neurological and regional complications groups.Results: Among the 43 patients with CN who underwent surgery, the transcortical (72.1%) or transcallosal (25.6%) approach was used. There were 18 patients (41.9%) who complained about postoperative neurological complications, including motor weakness (25.6%), memory deficit (18.6%), aphasia (7.0%), and seizure (4.7%). In addition, 18 patients suffered postoperative regional complications such as hydrocephalus (2.3%), hematoma (34.9%), infection (4.7%), and subcutaneous hydrops (2.3%). Only one-quarter of patients had suffered permanent surgical complications. The majority of patients recovered from the deficit and could turn back to normal life. There were no significant differences in the clinical outcomes between transcortical and transcallosal approaches. At a median follow-up of 61.8 months, the 5-year overall survival and progression-free survival were 87.0 and 74.0%, respectively. A multivariate Cox model analysis showed that the extent of resection was not related to progression-free survival. However, the extent of resection was significantly associated with overall survival, and gross total resection decreased the risk of death.Conclusions: Patients with CN show favorable outcomes after surgery. The transcortical and transcallosal approaches have similar postoperative complication rates and long-term follow-up outcomes. In terms of long-term prognosis, maximal safety resection should be the first choice of CN.

Initial report of Radiation Therapy Oncology Group (RTOG) 9802: Prospective studies in adult low-grade glioma (LGG)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 1500-1500 ◽  
Author(s):  
E. G. Shaw ◽  
B. Berkey ◽  
S. W. Coons ◽  
D. Brachman ◽  
J. C. Buckner ◽  
...  
Keyword(s):  
Overall Survival ◽  
Radiation Therapy ◽  
Survival Time ◽  
Prospective Studies ◽  
Radiation Therapy Oncology Group ◽  
Local Treatment ◽  
Progression Free Survival ◽  
Low Grade ◽  
Initial Report ◽  
Free Survival

1500 Background: Treatment of adult LGG is controversial. Favorable patients (pts) (age <40 years [yrs] who undergo gross total resection [GTR]) are typically observed. Unfavorable pts (age ≥40 who have subtotal resection [STR] or biopsy [B]) are usually given initial radiation therapy (RT), reserving chemotherapy (historically procarbazine, CCNU and vincristine [PCV]) for recurrence. In 1998, the RTOG, in conjunction with SWOG, NCCTG, and ECOG initiated prospective studies of adult LGG, the results of which are reported herein. Methods: Favorable pts were observed postoperatively in a single arm Phase II study (Arm 1). Unfavorable pts were stratified by age, histology, KPS, and presence/absence of contrast enhancement on preoperative magnetic resonance imaging and randomized to either RT alone (54Gy in 30 fractions to a local treatment field) (Arm 2) or RT followed by 6 cycles of standard dose PCV (Arm 3). Reported results include overall survival (OS) rate, median overall survival time (MOST), progression-free survival (PFS) rate, and median progression-free survival time (MPFST). Survival data are compared using Wilcoxon p-values. Results: A total of 362 eligible/analyzable pts were accrued between 1998 and 2002. Median follow-up time is 4 years. For the 111 favorable pts observed on Arm 1, OS at 2- and 5-yrs is 99% and 94%. PFS at 2- and 5-yrs is 82% and 50%. For the 251 unfavorable pts on Arms 2 (RT alone) and 3 (RT+PCV), there was no difference in OS or PFS. OS at 2- and 5-yrs was 87% and 61% with RT alone versus (vs) 86% and 70% with RT+PCV (p=0.72). MOST was not reached in RT alone pts and was 6.0 yrs in RT+PCV pts. PFS at 2- and 5-yrs was 73% and 39% with RT alone vs 72% and 61% with RT+PCV (p=0.38). MPFST was 4.0 yrs with RT alone vs 6.0 yrs with RT+PCV. Acute grade 3–4 toxicity occurred in 9% of pts who received RT alone, 67% who received RT+PCV (mostly hematologic). There were no treatment deaths on either arm. Conclusions: 5-yr PFS was poor in all three arms ranging from 39% to 61%. Only half of favorable pts were disease-free at 5 yrs. In unfavorable pts, there was no OS advantage with the addition of PCV to RT. Both PFS and MPFST were better with the addition of PCV, but not significantly. Analysis of outcome by 1p19q status is pending. No significant financial relationships to disclose.

Early Consolidation with Myeloablative Radiochemotherapy Followed by Autologous Stem Cell Transplantation in First Remission Significantly Prolongs Progression-Free Survival in Mantle Cell Lymphoma - Long Term Follow up of a Prospective Randomized Trial of the European MCL Network.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 7-7 ◽  
Author(s):  
Martin H. Dreyling ◽  
Georg Lenz ◽  
Eva Schiegnitz ◽  
Achiel van Hoof ◽  
Christian Gisselbrecht ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Cell Lymphoma ◽  
Progression Free Survival ◽  
Advanced Stage ◽  
Free Survival ◽  
Mantle Cell ◽  
First Remission

Abstract Mantle cell lymphoma (MCL) is a distinct subtype of malignant lymphoma with an especially poor prognosis and a median survival of only 3–4 years. In 1996, the European MCL Network initiated a randomized trial to improve the otherwise dismal outcome of MCL, comparing early consolidation with myeloablative radiochemotherapy (TBI 12 gray, cyclophosphamide 120 mg/kg bw) followed by autologous stem cell transplantation (ASCT) to a conventional a -interferon maintenance (6x106 IE IFNa 3x weekly) in first remission after a CHOP-like induction regimen. Until March 2004, a total of 269 previously untreated patients (up to 65 years) were randomized upfront. 189 (82%) of 230 patients with advanced stage MCL completed initial induction chemotherapy and 142 (75%) achieved either a complete (45 pts., 24%) or partial response (97 pts, 51%). 122 pts proceeded to consolidation therapy, 62 pts received ASCT consolidation and 60 patients were assigned to IFN maintenance. Patients in the ASCT study arm experienced a significantly longer progression-free survival (PFS) as compared to patients in the IFNa arm. The PFS at 2 years was 73% after ASCT as compared to only 43% in the IFNa arm (p = 0.0108). Similar results were achieved in the intent to treat analysis of all initially randomised MCL patients (p=0.0001). Accordingly, this advantage resulted in a trend towards an improved overall survival (OS) in the ASCT arm. After a follow-up of up to nearly 7 years (median follow-up of patients: 2.8 years), 3 year survival after ASCT was 83% in comparison to 77% under IFNa maintenance (p = 0.18). As expected, acute toxicity was higher in the ASCT group with an early mortality of 4.8%, whereas long-term effects were more frequently encountered under IFNa maintenance. Conclusion : In first line treatment of advanced stage MCL, dose-intensified consolidation with myeloablative radiochemotherapy followed by ASCT after CHOP-like induction results in a significant prolongation of PFS. Current study concepts evaluate the benefits of combined immuno-chemotherapy to further improve the overall survival.

Long-Term Outcomes of Autologous Transplantation in Multiple Myeloma: Prognostic Significance of Complete Response.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3126-3126
Author(s):  
Marta Krejci ◽  
Roman Hajek ◽  
Zdenek Adam ◽  
Ludek Pour ◽  
Lenka Zahradova ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Prognostic Significance ◽  
Progression Free Survival ◽  
Complete Response ◽  
Advisory Committees ◽  
Term Survival ◽  
Free Survival ◽  
Different Response

Abstract Abstract 3126 Background: Autologous stem cell transplantation (ASCT) after high-dose melphalan 200mg/m2 has got an important role in the treatment of symptomatic multiple myeloma (MM). The prognostic significance of achieving complete response (CR) after ASCT was cause of great debate for a long time. Some studies have shown the strong prognostic significance of achieving CR in MM, but other studies have failed to correlation between strength of the response and outcome. Aim: In this report we describe the long-term outcome of cohort 232 MM patients (pts) after ASCT with aim to establish the actual prognosis for the different response categories and to analyse other factors that might predict for long-term survival. Methods: We evaluated 232 pts with newly diagnosed symptomatic MM who received ASCT as a part of the first-line treatment between 1995 and 2005, median follow-up from ASCT was 131 months (range 61–195). Results: Following ASCT, overall response rate was 90% (202/232), 23% (52/232) of pts were in complete remission (CR), very good partial response (VGPR) was achieved in 45% of pts (100/232), partial response (PR) in 22% of pts (50/232), minimal response (MR) or stable disease (SD) in 10% of pts (22/232). Median progression-free survival (PFS) and overall survival (OS) from ASCT were 30.8 and 71.9 months, respectively. Progression-free survival at 12 years after ASCT in different response categories was 41% for pts with CR, 11% for pts with VGPR and 10% for pts with PR. Overall survival at 12 years after ASCT was 51% for pts with CR, 22% for pts with VGPR and 20% for pts with PR. The achievement of CR after ASCT was independent factor for long-term survival, significance differences in OS and PFS were found between CR and non-CR groups (P under 0.001 and P under 0.001, respectively). On multivariate analysis, the other factors associated with significantly better OS were ISS stage under III (P = 0.002), no presence of renal impairment (P = 0.008), age under 60 years (P = 0.001), no presence of deletion 1q21 (P = 0.029) and lenalidomide treatment in the post-transplant relapse (P = 0.002). Conclusion: The achievement of complete response after ASCT in multiple myeloma is the most important prognostic factor, even after long-term follow-up. The relapse rate is low in patients who remained in CR after 12 years from ASCT. A long-term complete remission should be a goal of treatment. Disclosures: Hajek: Merck: 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; Janssen Cilag: Honoraria.

Long-Term Outcome of a Prospective Study of Bortezomib, Dexamethasone and Rituximab (BDR) in Previously Untreated, Symptomatic Patients with Waldenstrom's Macroglobulinemia

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1833-1833 ◽  
Author(s):  
Steven P Treon ◽  
Kirsten Meid ◽  
Joshua Gustine ◽  
Christopher J Patterson ◽  
Jeffrey V. Matous ◽  
...  
Keyword(s):  
Overall Survival ◽  
Peripheral Neuropathy ◽  
Proteasome Inhibitor ◽  
Progression Free Survival ◽  
Free Survival ◽  
Major Response ◽  
Median Serum ◽  
Serum Iga

Abstract Background: Proteasome-inhibitor (PI) based therapy is highly effective and widely utilized in the treatment of Waldenstrom's Macroglobulinemia (WM), though published data on the long-term impact of PI-based therapy, including treatment-related peripheral neuropathy and secondary malignancies remains limited. Methods: We performed a prospective, multicenter study of bortezomib, dexamethasone and rituximab (BDR) in symptomatic, previously untreated WM patients. Treatment consisted of bortezomib 1.3 mg/m2 administered intravenously along with dexamethasone 40 mg on days 1, 4, 8, and 11; and rituximab 375 mg/m2 on day 11 as part of a 21-day cycle for 4 consecutive cycles as induction therapy. Maintenance therapy followed 12 weeks after induction therapy, and consisted of one cycle of BDR therapy every 12 weeks for a total of 4 cycles. Dose reduction or drug omission was permitted for toxicity. Herpes zoster prophylaxis and H2-blocker were required. Results: Twenty-three patients received a median of seven cycles of treatment. The median baseline characteristics were as follows: age 66 years; bone marrow involvement 55%; serum IgM 4,830 mg/dL; serum IgA 45 mg/dL; serum IgG 418 mg/dL; hemoglobin 10.1 g/dL; and B2M 3.3 mg/L. Extramedullary disease was present in 4 (17%) patients. Following treatment, median serum IgM levels declined to 557 mg/dL (p<0.001), and median hemoglobin levels rose to 14.3 g/dL (p=0.001) at best response. At last assessment, the median serum IgA and IgG were 36 and 476 mg/dL (p=0.66 and 0.28, respectively versus baseline). Using updated consensus response criteria (Owen et al, BJH 2013), the overall and major response rates were 96% and 91%, respectively, and categorical responses were as follows: CR (N=4); VGPR (N=8); PR (N=9); MR (N=1). The median time to response was 1.4 months. With a median follow-up of 8.5 years, the median time to progression was 5.5 years, with an estimated 5-year progression free survival rate of 57% (95% CI 32-72%). Patients attaining a CR showed a longer progression-free survival interval (long rank p=0.03). The 5-year overall survival was 95% (95% CI 72-99%). Kaplan Meier curves for progression-free (PFS) and overall survival (OS) are shown in Figure 1. Four patients died during the follow-up period, with only one death related to WM (amyloid progression). Three patients had invasive malignancies that occurred at 29.5 (N=1; Breast CA); 44.7 (N=1; Prostate CA); and 83.8 (N=1; Vulvar CA) months following initiation of protocol therapy. No unexpected toxicities occurred. The most common grade >2 toxicities were as follows: peripheral neuropathy (N=16); neutropenia (N=13); infections without neutropenia (N=13); thrombocytopenia (N=10) and steroid related hyperglycemia (N=6). Discontinuance of bortezomib occurred in 14 (60%) patients for peripheral neuropathy; dexamethasone for steroid intolerance in 3 (13%) patients; and rituximab for antibody-related neutropenia in one patient (4%). For the 16 patients experiencing bortezomib related peripheral neuropathy, neuropathic complaints resolved (N=8); decreased to Grade 1 (N=5); remained unchanged (N=2); or were unevaluable (N=1) with prolonged follow-up. Conclusions: BDR is a highly effective regimen producing high overall and major response rates, as well as long progression-free and overall survival intervals in previously untreated, symptomatic patients with WM. No unexpected toxicities were encountered. Secondary malignancies did not appear associated with protocol therapy. Reversible neurotoxicity constituted the most common adverse event associated with BDR using a twice-weekly schedule of administration of bortezomib, and resulted in high rates of proteasome-inhibitor discontinuance. Efforts to identify more neuropathy sparing approaches, including alternative schedules and routes of bortezomib administration, as well as novel neuropathy sparing proteasome-inhibitors are warranted given these encouraging long-term efficacy findings in WM. Disclosures No relevant conflicts of interest to declare.

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