Rituximab, Fludarabine, Mitoxantrone, and Dexamethasone (R-FND) for Relapsed Indolent Lymphomas (RIL).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 941-941 ◽  
Author(s):  
F.B. Hagemeister ◽  
P. McLaughlin ◽  
L. Fayad ◽  
F. Samaniego ◽  
N. Dang ◽  
...  
Keyword(s):  
Treatment Options ◽  
Median Number ◽  
Autologous Stem Cell Transplant ◽  
High Dose ◽  
Cell Transplant ◽  
Free Survival ◽  
Number Of Cycles ◽  
The One ◽  
Indolent Lymphomas

Abstract Optimal therapy for patients (pt) with B-cell RIL remains controversial, and many treatment options include rituximab (R). Based on phase I–II studies of FND (fludarabine 25 mg/m2, d1–3; mitoxantrone 10 mg/m2, d1; dexamethasone 20 mg d1–5) treatment for RIL in which we observed a 48% CR rate, we studied the combination of R (375 mg/m2 d1) and FND for pt with RIL. Pt could not have received prior fludarabine, and were eligible if they had not previoiusly received R or had a response lasting at least 6 months (mo) to prior treament with R. Cycles were repeated every 4 weeks, and required an absolute neutrophil count of 1,000 and a platelet count of 100,000 to administer each cycle. Forty-two pt were entered onto this trial; however, one never received therapy after signing consent, and two were deemed ineligible after signing consent because of low cardiac ejection fractions (EF). All pt underwent biopsy prior to therapy; histologies included follicular gr1–3 in 30 pt, small lymphocytic in 7, marginal zone in 2. The median age was 58 (range 39–84) and median prior therapies 1 (range 1–3). The median number of cycles of R-FND delivered per patient was 6 (range 1–8). Of the 39 eligible and evaluable pt, 19 entered CR and 9 CRu for a CR/CRu rate of 72%, and 9 entered PR (23%) for an overall response rate of 95%. One had stable disease (SD), and one progression (PD). Eight underwent high dose therapy followed by autologous stem cell transplant (SCT) following a response to R-FND therapy. Five of these had achieved CR/CRu with R-FND after 1–6 cycles, and 3 PR after 2–6 cycles. In all, 14 of the 37 responders to R-FND (37%) have had progression; however, none of the 8 who underwent SCT has had progression, nor has the one with SD. In, 24 (62%) still remain free of progression with a median follow-up for living pt of 32 mo. In all, 6 pt have died of PD, including 4 who were ineligible for or refused SCT. The 2-year failure-free survival (FFS) and overall survival (OS) results for all pt are 66% and 90%. The 2-year FFS for responders is 66%, and the 2-year OS for all pt, with pt undergoing SCT censored at time of SCT is 81%. As expected, the main toxicity following R-FND was hematologic: gr 4 neutropenia occurred in 15 pt and in 15 of 130 cycles for which information is available, and gr 3–4 thrombocytopenia in 5 pt and in 6 cycles. In all, 13 of the 28 responders received less than 6 cycles of therapy; reasons included prolonged thrombocytopenia in 4, early SCT in 6, asymptomatic decrease in EF in one, and physician’s choice in 2. No patients died of acute toxicity while receiving R-FND. We conclude that 1) R-FND is a very active and well tolerated regimen for relapsed indolent lymphomas 2) Results appear very favorable compared to prior studies with FND 3) In this population, patients receiving R-FND were able to undergo SCT, and had very favorable outcomes.

Retrospective Study of the Efficacy of Bortezomib in Primary Systemic Amyloidosis.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4953-4953
Author(s):  
Francis Buadi ◽  
Martha Q. Lacy ◽  
Angela Dispenzieri ◽  
Shaji Kumar ◽  
Suzanne Hayman ◽  
...  
Keyword(s):  
Plasma Cell ◽  
Median Number ◽  
Autologous Stem Cell Transplant ◽  
Primary Amyloidosis ◽  
Cell Transplant ◽  
Hematologic Response ◽  
Bortezomib Treatment ◽  
Organ Response ◽  
Number Of Cycles

Abstract Abstract 4953 Introduction Primary systemic (AL) amyloidosis occurs as a result of the production a monoclonal protein by a clonal plasma cell or B-cell proliferative disorder. Reduction or complete eradication of the underlying clonal cell disorder is essential for an organ response. Melphalan/ dexamethasone or high dose chemotherapy with autologous hematopoietic stem transplant is currently considered the standard of care. Bortezomib a proteosome inhibitor is effective in reducing or eradication clonal plasma cells and has been shown to produce high complete hematologic response (CHR) rates in multiple myeloma. We therefore hypothesized that Bortezomib will produce a high CHR rate and hence a higher organ response in patients with AL. Material and Methods Our amyloidosis data base which is prospectively collected was searched for patients with primary amyloidosis (AL) who were treated with Bortezomib containing regimen during their disease course. We identified 20 patients. We then assessed clinical features, hematologic and organ response based on the amyloidosis consensus working group criteria. We also evaluated overall survival and time to next therapy. Results We identified 20 patients who received a Bortezomib containing regimen. The median age at diagnosis was 57 yr (range 43 - 79). There were 12 (60%) males. All patients had clonal plasma cell disorder except one patient with lymphoplasmacytic lymphoma. Median bone marrow plasma cell involvement was 10%. The amyloid protein was Lambda light chain in 12 patients and Kappa in 6 patients. Data was missing in 2 patients. The median serum m-spike was 0.5g/dL (range 0 to 3.5). The median number of organs involved was 1 (range 1 – 4). Nine patients had 2 or more organs involved. The specific organs involved were Kidney (13), Cardiac (12), Nerve (5) and liver (2). Median number of prior regimen was 1(range 0 to 3). Seven patients had received no prior therapy. The remaining 13 patients had received various treatments including oral Melphalan/dexamethasone (9), Lenalidomide/dexamethasone (3), Thalidomide/dexamethasone (1) and one patient who received R-CHOP for underlying lymphoplasmacytic lymphoma. Four patients had received a prior autologous stem cell transplant. The median time form diagnosis to Bortezomib treatment was 5 months. The Bortezomib regimen was mainly Bortezomib/dexamethasone (17patients), Bortezomib/Thalidomide/dexamethasone (1), Bortezomib/cyclophosphamide/dexamethasone (1). The Bortezomib was given mainly in the standard dosing 1.3mg/m2 days 1, 4, 8, and 11. Treatment was well tolerated. Hematologic response was seen in 17 patients including CHR (11), VGPR (3), PR (1), and MR (2). Thus resulting in a better than PR response of 75%. Three patients had no response. The median number of cycles to best hematologic response was 4 (range 1 – 9). The median total number of cycles administered was 4 (range 1 – 10). Organ response was seen in 10 patients (50%). These were mainly partial responses was seen primarily in patients with renal amyloidosis. Median time to next treatment was 7.5 months (95% CI: 4-9). Seven patients have received further therapy after their Bortezomib treatment. Three patients received consolidation treatment with Autologous PBSCT although they had all achieved VGPR or CHR. The other four received salvage chemotherapy for disease progression or lack or response, BMT (1), FCR (1), Pomalidomde/dexamethasone (1) and Melphalan/dexamethasone (1). Median follow up of all patients from diagnosis is 12 months (range 2 – 64). The median survival from diagnosis is estimated at 44.7 months (95% CI; 29.1 – 64.8). Median follow up from Bortezomib treatment is 5 months and median survival from Bortezomib treatment has not been reached. Conclusion Bortezomib produced high hematologic response in this population of patients. Organs response was seen in 50% of patients. The durability of these responses is not known, because of the short follow up time. This study suggests that Bortezomib containing regimen may be beneficial in amyloidosis patients. A larger prospective study, looking at single agent Bortezomib or in combination with alkylator agents compared to standard melphalan/dexamethasone or autologous stem cell transplant is needed to help define the role of Bortezomib in primary amyloidosis. Disclosures Lacy: celgene: Research Funding. Gertz:celgene: Honoraria; millenium: Honoraria, Membership on an entity's Board of Directors or advisory committees.

Is Rituximab Needed With High Dose Chemotherapy and Autologous Stem Cell Transplant When Patients With Non-Hodgkin’s Lymphoma Have Been Exposed To It?

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5552-5552
Author(s):  
Zartash Gul ◽  
Stephan Anderson ◽  
Stacey Slone ◽  
Saurabh Chhabra ◽  
Gregory Monohan ◽  
...  
Keyword(s):  
Research Funding ◽  
Cell Lymphoma ◽  
Disease Free Survival ◽  
High Dose Chemotherapy ◽  
Autologous Stem Cell Transplant ◽  
High Dose ◽  
Cell Transplant ◽  
Free Survival ◽  
Disease Free

Abstract Introduction The value of Rituximab with High dose chemotherapy and autologous stem cell transplant (auto-HCT) has been evaluated in some retrospective studies. It is noted that the addition Rituximab to auto-HCT results in significant improvement in overall (OS) and disease free survival (DFS). However, it is unclear that the addition of Rituximab with auto-HCT would result in significant benefit in patients who have received prior Rituximab based therapy. Methods We retrospectively evaluated twenty seven consecutive patients who had B cell non-Hodgkin's lymphoma (NHL) and underwent auto- HCT at Markey cancer center between January 2010 and December 2012. All patients received 375 mg/m2of Rituximab with chemotherapy. Rituximab was not administered with high dose chemotherapy (BEAM: BCNU, Etoposide, Cytarabine and Melphalan) prior to auto-HCT. All patients received GCSF starting day 5 after auto-HCT. Results There were 27 patients who underwent auto-HCT for NHL. Median age of the patients was 60 years (36-72 years). Nineteen patients were male and 8 patients were female. Fifteen patients were in complete remission (CR) and the rest were in partial remission (PR). Patients had: Diffuse large B cell lymphoma (DLBCL=11 patients): Mantle cell lymphoma (MCL=13 patients): follicular lymphoma (3 patients). Median CD 34 count of infused cells was 4.14 x 106 cell/kg (2.26- 9.45). Median time to neutrophil recovery was 11 days (9-14). Median lymphocyte count at day 30 after auto HCT was 1130 x 10 6/l (320- 5180). After a median follow up of 7.9 months (3.0- 32.4) eight patients had relapsed. Five patients who had relapsed had refractory disease before auto-HCT. Non -Relapse mortality (NRM) is shown in figure 1. Median overall survival and disease free survival were not reached. Seventy percent patients had not relapsed. We did not find any factors associated with relapse. Conclusion We performed a retrospective study to evaluate the impact of Rituximab with high dose chemotherapy and in patients with NHL. Review of literature showed that median 2 year and 5 year OS was 80% and 69% in patients who received Rituximab with auto HCT. Median 2 year DFS was 67%. In our study 70% patients were relapse free at a median follow up of 8 months. We would need a longer follow up to determine the efficacy of Rituximab with auto- HCT in patients with NHL who had prior exposure to Rituximab. Disclosures: Off Label Use: The use of Thymoglobulin® for GVHD prevention. Hayslip:Sanofi: Research Funding; Janssen: Research Funding; Pfizer: Research Funding; Celgene: Research Funding.

scholarly journals NCOG-59. PROGRESSION-FREE SURVIVAL AS A PRIMARY OUTCOME MEASURE TO COMPARE CONSOLIDATIVE STRATEGIES IN RELAPSED/REFRACTORY PRIMARY CNS LYMPHOMA

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii142-ii142
Author(s):  
Alipi Bonm ◽  
Alec Gibson ◽  
Leona Holmberg ◽  
Marco Mielcarec ◽  
Tresa McGranahan ◽  
...  
Keyword(s):  
Primary Cns Lymphoma ◽  
Progression Free Survival ◽  
Disease Diagnosis ◽  
Median Number ◽  
Autologous Stem Cell Transplant ◽  
Cns Lymphoma ◽  
High Dose ◽  
Cell Transplant ◽  
Free Survival ◽  
Effect Of Age

Abstract Relapsed or refractory primary CNS non-Hodgkin’s lymphoma (rrPCNSL) is a rare and challenging malignancy for which better evidence is needed to guide management. We present a retrospective cohort of 70 consecutive patients with rrPCNSL treated at the University of Washington between 2000-2020. HIV positive and secondary CNS lymphoma patients were excluded. During a median follow-up of 19.8 months, median overall survival (OS) was 18.30 months and median progression-free survival (PFS) was 12.67 months. At all stages of disease (diagnosis, first relapse, multiple relapses), PFS was an excellent predictor of OS. There was a small effect of age < 70 on PFS after initial diagnosis (PFS1), but no effect on PFS after first (PFS2) or subsequent (PFS3+) relapses. There was no effect of age < 60 on PFS1, PFS2, or PFS3+. Patients reinduced with high-dose methotrexate-based (HD-MTX) regimens had an overall response rate (ORR) of 86.7% and median PFS 17.2 months. For patients who responded to reinduction therapy, those consolidated with autologous stem cell transplant (ASCT) had median PFS of 30.3 months (n=11) compared with 12.1 months for other consolidation strategies (n=9), and 9.0 months for no consolidation (n=20). Although patients receiving ASCT were younger, KPS, sex, and the median number of recurrences were similar between consolidation groups. We conclude that PFS is a useful endpoint for rrPCNSL which predicts OS and is not associated with age. Using PFS as an endpoint, we did not detect a benefit to any consolidation strategy other than ASCT.

Outcomes and Treatments of Relapsed AL Amyloidosis Following Stem Cell Transplant

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1858-1858 ◽  
Author(s):  
Rahma Warsame ◽  
Soo-Mee Bang ◽  
Shaji K. Kumar ◽  
Martha Q Lacy ◽  
Francis K Buadi ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplant ◽  
Plasma Cells ◽  
Conflicts Of Interest ◽  
Treatment Options ◽  
Autologous Stem Cell Transplant ◽  
Al Amyloidosis ◽  
Cell Transplant ◽  
Post Transplant

Abstract Abstract 1858 Systemic light chain amyloidosis (AL amyloidosis) is a condition where clonal plasma cells produce misfolded insoluble immunoglobulin light chains that deposit in various organs causing progressive organ dysfunction. Chemotherapy and autologous stem cell transplant (ASCT) when eligible is the standard treatment options for patients with AL amyloidosis. There are several studies who report long term outcomes of patient post ASCT. However, there is a paucity of literature describing the outcomes of patients who have received ASCT but have relapsed. We performed a retrospective study to assess the outcomes and treatment regimens employed following relapse after ASCT. Between 1996 and 2009, 410 patients received ASCT at the Mayo Clinic as first line therapy. Of those 410 patients 42 patients died within 3 months of transplant, 64 patients died without documented relapse, 158 patients were alive without documented progression, and 146 patients had documented progression. Those 146 patients are the subject of our study. The median time to hematologic relapse was 2 years (range: 0.2–15.5 years). At relapse, 59 patients were treated with IMiD based therapy, 36 with alkylator based therapy, 24 with bortezomib, 15 with steroids, and 5 with second ASCT. The respective hematologic response rates were 58%, 33%, 50%, 53%, and 60%. The remaining six patients were not evaluable for response for one other following reasons: organ transplants; no further therapy; inevaluable disease. With a median post relapse follow up of 3.6 years, the median overall survival (OS) from the first post ASCT relapse was 4.6 years. The median post transplant follow up was 6.1 years, the median OS for these patients was 7.3 years from the time of transplant. These data provide novel information about outcomes after SCT relapse, which should be useful not only for patients and doctors but also for investigators designing studies for salvage therapies post-transplant. Disclosures: No relevant conflicts of interest to declare.

Tandem Autologous Stem Cell Transplantation in Chemorefractory Multiple Myeloma

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4554-4554
Author(s):  
Catherine Garnett ◽  
Chrissy Giles ◽  
Osman Ahmed ◽  
Maialen Lasa ◽  
Holger W. Auner ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Stem Cell Transplant ◽  
Progression Free Survival ◽  
Autologous Stem Cell Transplant ◽  
Cell Transplant ◽  
Free Survival

Abstract Abstract 4554 High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is currently standard treatment for younger patients with multiple myeloma, resulting in improved survival and response rate compared to conventional chemotherapy. Disease relapse, however, remains almost inevitable and thus the role of two successive (tandem) autologous stem cell transplants has been evaluated in chemorefractory patients as a means of prolonging duration of disease response. We retrospectively analysed the results of nine patients with chemorefractory disease treated at a single UK institution who received tandem ASCT between January 1998 and February 2009. There were six men and three women. Median age at diagnosis was 56 years (range, 42–65 years). Paraprotein isotype was IgG in eight patients and IgA in one patient. Median serum paraprotein level was 41g/L (range 12–73g/L) at presentation. At time of 1st transplant six patients were in stable disease (SD) and three had evidence of progressive disease. Conditioning melphalan dose was 140mg/m2 in all but two patients who received 110mg/m2 and 200mg/m2. Median time between transplants was 3.7 months (range 2.3–6.4 months) with PR and SD being observed in 2/9 and 7/9 patients at time of 2nd transplant. None of the patients reached complete response (CR). One patient received melphalan 140mg/m2 prior to 2nd transplant. The remaining patients received melphalan 200mg/m2. Median follow up after tandem transplant was 54.3 months (range 15.6 –143.6 months). No treatment related mortality was reported. At the time of analysis, six patients were still alive and under follow up with an overall survival (OS) figure for the group of 52% at 10 years from diagnosis (Figure 1). Median progression free survival (PFS) was 20 months from 2nd transplant (range 6.7–62.6 months) (Figure 2). Tandem autologous stem cell transplant in chemorefractory patients has resulted in overall survival similar to autologous stem cell transplant in chemosensitive patients and should be considered in patients with chemorefractory disease. Figure 1: Overall survival from diagnosis in patients receiving tandem autologous stem cell transplant for multiple myeloma Figure 1:. Overall survival from diagnosis in patients receiving tandem autologous stem cell transplant for multiple myeloma Figure 2: Progression free survival following tandem transplant Figure 2:. Progression free survival following tandem transplant Disclosures: No relevant conflicts of interest to declare.

Mantle cell lymphoma (MCL): Induction therapy with HyperCVAD/High-dose methotrexate and cytarabine (M-C) (±rituximab) improves results of autologous stem cell transplant in first remission

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7511-7511 ◽  
Author(s):  
J. Vose ◽  
F. Loberiza ◽  
P. Bierman ◽  
G. Bociek ◽  
J. Armitage
Keyword(s):  
Stem Cell ◽  
Induction Therapy ◽  
Stem Cell Transplant ◽  
Disease Free Survival ◽  
Autologous Stem Cell Transplant ◽  
High Dose ◽  
Cell Transplant ◽  
Free Survival ◽  
Disease Free

7511 Background: Although patients (pts) with MCL have a high response rate to standard chemotherapy, they continue to relapse with no plateau in long term disease-free survival. The use of dose intense induction therapy such as HyperCVAD (M-C) ±Rituximab(R) and high-dose therapy and stem cell may improve these results. In this analysis the outcomes of pts receiving a standard anthracycline induction therapy or HyperCVAD(M-C)(±R) then followed by a stem cell transplant in first complete (CR1) or partial remission (PR1) were compared. Methods: Between 6/91 and 11/05, 124 pts with MCL received high-dose chemotherapy and a stem cell transplant. Of these pts, 80 received an autologous stem cell transplant in CR1 (N = 47) or PR1 (N = 33). A standard anthracycline based CHOP-like (±R) induction therapy was given to 48 pts compared with 32 pts who received HyperCVAD(M-C)(±R) prior to transplant. Results: The median age of pts was 56 years (range 33–70). The male:female ratio was 33:57. Bone marrow involvement prior to conditioning was present in 52% of pts. An elevated lactic dehydrogenase (LDH) was present in 58% of pts. 65% of patients received one prior chemotherapy before coming to stem cell transplant. The median follow up of pts is 38 months (range 3–143). Progression-free survival (PFS) and overall survival (OS) are outlined in table 1 . Characteristics associated with an improved OS by multivariate analysis included receiving HyperCVAD induction (p = 0.04), transplant in CR1 (p = 0.009), ≤ 3 prior chemotherapy regimens (p = 0.02) and no B symptoms at transplant (p = 0.05). Conclusions: To improve the long term disease free survival for pts with MCL, Hyper-CVAD(M-C)(±R) induction should be given to eligible patients with autolgous stem cell transplantation in CR1. [Table: see text] No significant financial relationships to disclose.

scholarly journals Alternative Consolidation Strategy after High Dose Methotrexate, Rituximab and Temozolamide in Primary CNS Lymphoma - the Henry Ford Experience

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 5-5
Author(s):  
Joyce Philip ◽  
Shivani Sharma ◽  
Vijayalakshmi Donthireddy
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplant ◽  
Primary Cns Lymphoma ◽  
Autologous Stem Cell Transplant ◽  
Cns Lymphoma ◽  
High Dose ◽  
Cell Transplant ◽  
High Dose Methotrexate ◽  
Dose Methotrexate

Background: Treatment for primary CNS lymphoma involves a methotrexate-based induction therapy followed by consolidation. The optimal consolidation treatment after induction with a high dose Methotrexate (HD-MTX), Rituximab and Temozolomide regimen has not been fully established. The CALGB 50202 regimen using Etoposide and Cytarabine consolidation was associated with significant toxicity. We sought to review the results of alternative consolidation regimens and evaluate the progression free survival and overall survival. Methods: A retrospective cohort study was conducted to evaluate the efficacy of alternative consolidation regimens such as autologous stem cell transplant and HDMTx alone. Patients diagnosed with primary CNS lymphoma between November 2012 and March 2019 were identified. All patients received the same induction chemotherapy based on the CALGB 50202 protocol. Data was collected for baseline characteristics, progression free survival and overall survival. Results: 38 patients had a diagnosis of primary CNS lymphoma. 15 patients received treatment as per the CALBG 50202 induction protocol with high dose Methotrexate, Rituximab and Temozolomide. Of the 15 patients, 11 patients (69%) achieved a complete remission (CR) after induction therapy. 7 patients received an autologous stem cell transplant for consolidation, 5 patients received HD-MTX alone for consolidation and one patient was placed on Lenalidomide maintenance. 2 patients did not receive any consolidation therapy due to progressive disease and/or death. At a median follow up of 2.7 years for the entire cohort, median PFS was 31.7+ months and median OS was 32.5+ months. At a median follow up of 2.7 years for patients who were consolidated with an autologous stem cell transplant, median PFS and median OS was 27.2+ and 32.5+ months respectively. At a median follow up of 5.5 years for patients who were consolidated with treatments other than transplant, median PFS and OS was 65.6+ months. There were no deaths attributed to treatment related toxicity. To date, 4 patients of the entire cohort have died, with a median survival time among surviving patients of 3.6 years (range, 0.68-7.05 years). There were no deaths attributed to treatment related toxicity. Conclusion: Patients with primary CNS lymphoma who received induction therapy as per CALGB 50202 regimen and received alternative consolidation therapies with either autologous stem cell transplant or HD-MTX based consolidation achieved prolonged PFS and OS comparable if not superior to the Etoposide and Cytarabine consolidation. Results of the ongoing CALGB 51101 trial will determine the utility of EA consolidation. Disclosures No relevant conflicts of interest to declare.

scholarly journals Efficacy of Osimertinib Plus Bevacizumab In Glioblastoma Patients With Simultaneous EGFR Amplification And EGFRvIII Mutation

2021 ◽  
Author(s):  
Daniel Jaramillo-Velásquez ◽  
Andrés F. Cardona ◽  
Alejandro Ruiz-Patiño ◽  
Carolina Polo ◽  
Enrique Jiménez ◽  
...  
Keyword(s):  
Overall Response Rate ◽  
Kinase Inhibitors ◽  
Progression Free Survival ◽  
Median Number ◽  
Resistance Pattern ◽  
Free Survival ◽  
Egfr Amplification ◽  
Egfr Tyrosine Kinase Inhibitors ◽  
Number Of Cycles

Abstract Background: Amplification of EGFR and its active mutant EGFRvIII are common in glioblastoma (GB). While EGFR and EGFRvIII play critical roles in pathogenesis, targeted therapy with EGFR-tyrosine kinase inhibitors (TKIs) or antibodies has shown limited efficacy. To improve the likelihood of effectiveness, we targeted adult patients with recurrent GB enriched for simultaneous EGFR amplification and EGFRvIII mutation, with osimertinib/bevacizumab at doses described for non-small cell lung cancer (NSCLC). Methods: We retrospectively explored whether previously described EGFRvIII mutation in association with EGFR gene amplification could predict response to osimertinib/bevacizumab combination in a subset of 15 patients treated at recurrence. The resistance pattern in a subgroup of subjects is described using a commercial NGS panel in liquid biopsy.Results: There were ten males (66.7%), and the median patient’s age was 56 years (range 38-70 years). After their initial diagnosis, 12 patients underwent partial (26.7%) or total resection (53.3%). Subsequently, all cases received IMRT and concurrent and adjuvant temozolomide (TMZ; the median number of cycles 9, range 6-12). The median follow-up after recurrence was 17.1 months (95% CI 12.3-22.6). All patients received osimertinib/bevacizumab as a second-line intervention with a median progression-free survival (PFS) of 5.1 months (95% CI 2.8-7.3) and overall survival (OS) of 9.0 months (95% CI 3.9-14.0). The PFS6 was 46.7%, and the overall response rate (ORR) was 13.3%. After exposure to the osimertinib/bevacizumab combination, the main secondary alterations were MET amplification, STAT3, IGF1R, PTEN, and PDGFR.Conclusions: While the osimertinib/bevacizumab combination was marginally effective in most GB patients with simultaneous EGFR amplification plus EGFRvIII mutation, a subgroup experienced a long-lasting meaningful benefit. The findings of this brief cohort justify the continuation of the research in a clinical trial. The pattern of resistance after exposure to osimertinib/bevacizumab includes known mechanisms in the regulation of EGFR, findings that contribute to the understanding and targeting in a stepwise rational this pathway.

Autologous stem cell transplant for primary CNS lymphoma results in prolonged progression free and overall survival

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7623-7623
Author(s):  
P. B. Johnston ◽  
B. P. O’Neill ◽  
S. M. Ansell ◽  
D. J. Inwards ◽  
L. F. Porrata ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Stem Cell Transplant ◽  
Primary Cns Lymphoma ◽  
Autologous Stem Cell Transplant ◽  
Cns Lymphoma ◽  
Cell Transplant ◽  
Free Survival ◽  
Additional Therapy

7623 Background: Survival for patient with primary CNS lymphoma (PCNSL), in general, is poor with patients requiring frequent chemotherapy treatments or receiving whole-brain radiation therapy, which can potentially result in significant neurologic decline and dementia. Because of the improved survival of high risk patients with aggressive lymphoma undergoing autologous stem cell transplant (ASCT), we began ASCT for patients with PCNSL in first or later remission with chemotherapy sensitive disease. We now report on outcomes of patients who have had at least 1 year follow up post ASCT. Methods: Between June, 2000 and September, 2004, 11 patients underwent ASCT for PCNSL. The medical records of consenting patients were abstracted for the following information. Median age at transplant was 47 years old (range 30–67). Median number of prior treatments 1 (range 1–3). Median time from diagnosis to transplant was 7.5 months (range 2.9 to 75.8). Median International Extranodal Working Study Group Prognostic Score: 2 (range 0–3). Disease status at transplant: First CR 5 patients, later CR or PR 6 patients. Results: Eleven patients underwent ASCT for PCNSL and have a minimum of 1 year follow-up. All patients received BEAM conditioning. Median follow up was 28.3 months. Four patients have relapsed at a median of 200 days (range 40–523). Of the patients who relapsed, one has died of disease progression and the remaining three are alive after additional therapy. Median overall survival and progression free survival from transplant have not been reached. Two year overall and event free survival are 89% and 61%, respectively. Conclusions: Although limited by patient selection and retrospective biases, this review suggests that ASCT for PCNSL demonstrates improved overall survival when compared to historical controls with similar PCNSL Prognostic Scores (2 year survival for patients from diagnosis with PS 2–3 was 48% in a prior published study). ASCT in first remission in patients with PCNSL appears promising and may limit the need for additional therapy which can be myelosuppressive or result in neurologic decline. No significant financial relationships to disclose.

Survival and toxicity outcomes in patients age 40 or older with relapsed metastatic germ cell tumors (mGCT) treated with high-dose chemotherapy (HDCT) and autologous peripheral-blood stem cell transplant (PBSCT).

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 522-522
Author(s):  
Nabil Adra ◽  
Costantine Albany ◽  
Rafat Abonour ◽  
Mohammad Issam Abu Zaid ◽  
Dannillo Pereira ◽  
...  
Keyword(s):  
Salvage Therapy ◽  
Germ Cell Tumors ◽  
Progression Free Survival ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Cell Transplant ◽  
Indiana University ◽  
Free Survival ◽  
Kaplan Meier

522 Background: HDCT plus PBSCT is effective salvage therapy for relapsed mGCT but has potential toxicity which can be more pronounced in older patients. We report survival and toxicity outcomes in pts with relapsed mGCT age ≥ 40 at time of HDCT. Methods: 440 consecutive pts with relapsed mGCT were treated with HDCT and PBSCT with tandem cycles at Indiana University (IU) between 2004-2017 per our previous reported regimen (N Engl J Med 2007; 357: 340-8). Kaplan-Meier methods were used for progression free survival (PFS) analysis. Results: 110 pts were age ≥ 40 while 330 pts were age < 40. Among pts age ≥ 40, median AFP was 6.6 (range, 1-2,709) and median hCG was 5.3 (range, 1-42, 453). Of the 110 pts age ≥ 40, 75 had complete remission without relapse during a median follow-up of 23 months. There were 3 treatment-related deaths. Conclusions: HDCT plus PBSCT is safe and effective salvage therapy in pts age ≥ 40 with relapsed mGCT. [Table: see text]

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