Tositumomab and I 131 Tositumomab Achieves Complete Remissions Lasting > 10 Years In Patients with Chemotherapy-Refractory Low-Grade and Transformed B-Cell Lymphomas

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3960-3960
Author(s):  
Mark S. Kaminski ◽  
Andrew D. Zelenetz ◽  
Oliver W. Press ◽  
Mansoor N. Saleh ◽  
John P. Leonard ◽  
...  
Keyword(s):  
B Cell ◽  
Research Funding ◽  
Response Duration ◽  
Complete Response ◽  
Median Number ◽  
Low Grade ◽  
Duration Of Response ◽  
Long Term Follow Up

Abstract Abstract 3960 Introduction: The efficacy and safety of tositumomab and iodine I 131 tositumomab (TST/I-131-TST), the Bexxar® Therapeutic Regimen, were evaluated in 60 patients (pts) with chemotherapy-refractory low-grade (LG) or transformed B-cell non-Hodgkin's lymphoma (B-NHL) who had received at least 2 chemotherapy regimens and had either not responded to (72%) or had progressed within 6 months of their last regimen (28%) (J Clin Onc 2001; 19:3918 and Blood 2004; Abstract 2631). The primary efficacy endpoint was comparison of the number of pts who had a longer duration of response to TST/I-131-TST with the number of pts with a longer duration of response to their last qualifying chemotherapy (LQC). Thirty-nine (65%) pts, including 20% who attained a complete response (CR), responded to TST/I-131-TST, compared to 17 (28%) pts, including 3% CR, after their LQC (p<0.001). Seventy-four percent of pts had a longer response duration after TST/I-131TST compared to the LQC. Four pts developed myelodysplasia (MDS), and 5 pts developed human anti-mouse antibodies (HAMA). We report final results of long term follow-up of these 60 pts. Patients and Methods: Pts were enrolled from 22 November 1996 to 06 March 1998. Pts alive at the last report date (1 March 2004) were followed for long-term safety and survival, and pts in remission at the last report date were followed for continued response. Results: Sixty pts received the dosimetric dose, and 58 of 60 pts received both the dosimetric and therapeutic doses of TST/I-131-TST. The median number of prior chemotherapies was 4 (range, 2–13). Fifty-nine of 60 (98%) pts had stage III/IV disease, 56% had bone marrow (BM) involvement, and 88% had ≥ two IPI risk factors at study entry. Thirty-six pts had LG B-NHL, 23 pts had a history of transformed B-NHL, and 1 pt had mantle cell NHL (MCL). Forty-eight (80%) pts have died, of whom 77% died due to lymphoma progression. Twelve pts were alive, and 6 pts were in CR at last follow-up. One pt withdrew consent for further follow-up but was in CR at 5.0 years, and the other 5 pts (4 LG, 1 transformed B-NHL) were in CR of ≥ 10 years' duration. The pts who continued in CR had received a median of 3 different prior chemotherapy regimens (range, 2–5), and no pts had received prior rituximab. For all 12 pts who attained CR, the median duration of response was 9.9 years (range, 0.7–11.7 years). Long-term toxicity included 7 pts who developed hypothyroidism. Secondary cancers included 1 lung adenocarincoma, 1 colon cancer, and 7 skin cancers which were reported previously. In addition, 1 developed a myeloproliferative disorder (MPD). No cases of MDS beyond the 4 previously reported were observed. Conclusion: A single course of TST/I-131-TST achieved durable remissions in chemotherapy-refractory LG and transformed B-NHL pts, with 5 of the 12 pts who achieved CR still in remission ≥ 10 years later. No additional cases of MDS were observed, but 1 pt developed a MPD since the last report. Thus, the final results of this study demonstrate that TST/I-131-TST is able to attain long-lasting durable CRs, with an acceptable toxicity profile, in a subset of pts with chemotherapy-refractory LG and transformed B-NHL. Disclosures: Kaminski: GlaxoSmithKline: Patents & Royalties, Research Funding. Zelenetz:GlaxoSmithKline: Research Funding. Press:GlaxoSmithKline: Research Funding; Spectrum Pharmaceuticals: Honoraria; Roche/Genentech: Honoraria. Saleh:GlaxoSmithKline, Novartis, Imcoline, Celgene: Honoraria, Speakers Bureau. Leonard:GlaxoSmithKline: Consultancy. Lister:GlaxoSmithKline: Chairman of Safety Monitoring Board for GSK. Horner:GlaxoSmithKline: Employment. Williams:GlaxoSmithKline: Employment. Lin:GlaxoSmithKline: Consultancy, Employment. Vleisides:GlaxoSmithKline: Employment. Knox:GlaxoSmithKline: Research Funding. Wahl:GlaxoSmithKline: Consultancy, Patents & Royalties; Nihon Medi Physics: Consultancy; Spectrum Pharmaceuticals: Consultancy; Naviscan PET systems: Consultancy; Threshold Pharmaceuticals: Equity Ownership. Vose:GlaxoSmithKline: Research Funding.

scholarly journals Mature Follow up from a Phase 2 Study of PI3K-Delta Inhibitor Idelalisib in Patients with Double (Rituximab and Alkylating agent)-Refractory Indolent B-Cell Non-Hodgkin Lymphoma (iNHL)

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1708-1708 ◽  
Author(s):  
Ajay K. Gopal ◽  
Brad S. Kahl ◽  
Sven de Vos ◽  
Nina D. Wagner-Johnston ◽  
Stephen J. Schuster ◽  
...  
Keyword(s):  
B Cell ◽  
Research Funding ◽  
Employment Equity ◽  
Non Hodgkin Lymphoma ◽  
Duration Of Response ◽  
Equity Ownership ◽  
Grade 3 ◽  
Systemic Therapies

Abstract Introduction: Rituximab-alkylator combinations are the standard therapies for patients (pts) with iNHL, however, refractory disease nearly uniformly develops. Once iNHL becomes “double-refractory” to both rituximab + alkylating agents, there are limited options to induce durable remissions. PI3K-delta signaling is critical for activation, proliferation and survival of B cells, and is hyperactive in many B-cell malignancies. Idelalisib, a selective oral inhibitor of PI3Kd, demonstrated considerable clinical activity in double-refractory iNHL (Gopal NEJM 2014). FDA granted accelerated approval for Idelalisib (Zydelig®) in patients who have received at least two prior systemic therapies with relapsed FL or SLL. Based on these encouraging initial results, we now describe long-term follow up, safety, and remission durations of this double-refractory iNHL population treated with idelalisib. Methods: Eligible iNHL pts included those with measurable disease refractory to both rituximab and an alkylating agent. Refractory was defined as lack of response to, or progression of lymphoma within 6 months of completion of index therapy, confirmed by imaging. Idelalisib 150 mg PO BID was administered continuously until disease progression or intolerance. Responses were evaluated by an independent review committee, using standard criteria (Cheson, 2007, and Owen 2013). The new data cutoff date for this analysis was June 2014, 20 months after the last patient enrolled. Results: Enrolled pts (N = 125) had a median age of 64 years and included follicular lymphoma (FL) n=72 (58%), small lymphocytic lymphoma (SLL) n=28 (22%), marginal zone lymphoma (MZL) n=15 (12%) and lymphoplasmacytic lymphoma (LPL)/Waldenstrom's macroglobulinemia (WM) n=10 (8%). The median number of prior therapies was 4 [range 2-12], including bendamustine/rituximab (BR) (n=60) and rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone (R-CHOP) (n=56) and autologous transplant (n=14). 81 pts (65%) had prior bendamustine, of which 61/81 (75%) were refractory. 112 pts (90%) were refractory to their last regimen, and 99 pts (79%) were refractory to ≥2 regimens. 38 pts (30%) had elevated LDH, and 33 pts (26%) had bulky disease >7 cm. The median time to progression from last prior therapy was 3.9 months. With a median exposure of 11.1 months (range 0.7 to 35.4), the overall response rate (ORR) is 56% (95% CI = 46.8-64.9) with 70 responders, comprising 12 CRs (9.6%), 58 PRs (46.4%). The median time to response was 1.9 months (time of first evaluation) and time to CR was 4.5 months. There were 43 pts with stable disease (SD) (34.4%). 90% of pts experienced some decrease in tumor burden. ORR for iNHL subtypes is: FL (54%), SLL (61%), MZL (47%), and LPL/WM (70%). CR rate for iNHL subtypes is: FL (14%), SLL (4%), MZL (7%), and LPL/WM (0%). Among responders, median DOR is 13.9 (0.03-31.3) months. DOR for iNHL subtypes in months (Figure 1) is: FL 11.8, SLL 13.9, MZL 18.4, and LPL/WM (not yet reached). Median PFS for all pts is 11.0 months, in comparison to a median PFS of the last prior regimen of 3.9 months (p<.0001). The median PFS for individual subtypes in months was: FL 11.0, SLL11.1, MZL 6.6, and LPL/WM 22.2. The median overall survival of all patients was 30.8 months. The adverse events include (total%/≥ grade 3%) diarrhea/colitis (50/18), fatigue (30/2), nausea (31/2), cough (32/0), pyrexia (30/2), dyspnea (18/5), rash (14/2), pneumonia (14/11), and pneumonitis (4/3). Based on central laboratory measurements, Grade ≥3 ALT/AST elevations occurred in 18 pts (14%). Drug was temporarily held in these pts, and 11/15 pts (73%) were re-treated without recurrence of ALT/AST elevation. Overall, 30 pts (24%) have discontinued therapy due to adverse events. Conclusions: The prolonged administration of idelalisib was well tolerated, had an acceptable safety profile, and was highly effective in inducing and maintaining remissions in double-refractory iNHL population with an ORR of 56%, PFS of 11 months, and DOR of 13.9 months. The response rate and long term duration of responses in the small number of subjects with LPL/WM is very promising, and will be evaluated in larger trials of this disease. The observed disease control compared to prior regimens suggests the potential for prolonged clinical benefit in this challenging patient population with unmet medical need. Figure 1: Duration of Response by Disease Group. Figure 1:. Duration of Response by Disease Group. Disclosures Gopal: Gilead Sciences: Research Funding. Off Label Use: Zydelig is a kinase inhibitor indicated for the treatment of patients with: 1) Relapsed chronic lymphocytic leukemia (CLL), in combination with rituximab, in patients for whom rituximab alone would be considered appropriate therapy due to other co-morbidities; 2) Relapsed follicular B-cell non-Hodgkin lymphoma (FL) in patients who have received at least two prior systemic therapies; and 3) Relapsed small lymphocytic lymphoma (SLL) in patients who have received at least two prior systemic therapies.. Kahl:Gilead Sciences: Research Funding. de Vos:Gilead Sciences: Research Funding. Wagner-Johnston:Gilead Sciences: Research Funding. Schuster:Gilead Sciences: Research Funding. Jurczak:Gilead Sciences: Research Funding. Flinn:Gilead Sciences: Research Funding. Flowers:Gilead Sciences: Research Funding. Martin:Gilead Sciences: Research Funding. Viardot:Gilead Sciences: Research Funding. Blum:Gilead Sciences: Research Funding. Goy:Gilead Sciences: Research Funding. Davies:Gilead Sciences: Research Funding. Zinzani:Gilead Sciences: Research Funding. Dreyling:Gilead Sciences: Research Funding. Holes:Gilead Sciences: Employment, Equity Ownership. Sorensen:Gilead Sciences: Employment, Equity Ownership. Godfrey:Gilead Sciences: Employment, Equity Ownership. Salles:Gilead Sciences: Research Funding.

scholarly journals Outcomes of Patients with Relapsed/Refractory (R/R) B-Cell Acute Lymphocytic Leukemia (ALL) Post Blinatumomab Failure

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1335-1335 ◽  
Author(s):  
Jenny Dahl ◽  
Hagop M. Kantarjian ◽  
Musa Yilmaz ◽  
Tapan Kadia ◽  
Guillermo Garcia-Manero ◽  
...  
Keyword(s):  
B Cell ◽  
Median Survival ◽  
Median Duration ◽  
Salvage Therapy ◽  
Research Funding ◽  
Clinical Characteristics ◽  
Complete Response ◽  
Best Response ◽  
Duration Of Response

Abstract Introduction: Blinatumomab is a first-in-class Bispecific T-cell engaging (BiTE) antibody targeting CD19-positive malignant cells and CD3-positive T cells. It has shown activity in both R/R B-cell ALL and with persistent minimal residual disease (MRD). However, despite a 50% response rate with blinatumomab, the duration of response is very short with many pts experiencing relapse. The goal of this study is to assess the outcome of patients with R/R B-cell ALL post blinatumomab failure. Methods: We reviewed 40 patients with R/R ALL treated with blinatumomab at our institution between 1/2012 and 1/2015. Of the 40 patients treated, 30 were either refractory (n=18) or lost their response (n=12) after initially achieving a complete response or complete response with incomplete count recovery (CRi). We analyzed the clinical characteristics and survival of these 30 patients who failed blinatumomab. Results: Clinical characteristics of the 30 patients with blinatumomab failure are summarized in Table 1. Best response to blinatumomab was CR in 9 pts and CRi in 3 with a median duration of response of 3 months (range, 1-8 months). After a median follow-up of 6.8 months (range 4.8- 31 months) from blinatumomab failure, 8 patients (27%) remain alive. The median overall survival was 6.4 months and the estimated 12-month survival rate was 36%. The median survival was 3 and 11 months for patients refractory to blinatumomab and those who relapsed after a previous response, respectively (p=0.179). Furthermore, there was a trend for better outcome post blinatumomab failure if the drug was administered as first, second, or third and beyond salvage therapy with a median survival of 19, 11, and 5 months, respectively (p= 0.248). Following blinatumomab failure, 11 patients received inotuzumab ozogamicin salvage therapy as a single agent in 5 or in combination with mini-hyper-CVD in 6 [Jabbour E et al; EHA 2015]. Eight patients responded for an overall response rate of 73% for a median duration of 6 months (range, 1.2-30 months). Overall, 9 patients underwent allogeneic stem cell transplant (allo-SCT), 5 of them post salvage therapy with inotuzumab. Seven of them remain alive in CR at the last follow-up. The 1-year survival rates were 83% and 11% for patients who received an allo-SCT and those who did not, respectively (p<0.001). Conclusions: Overall, the outcome of patients with R/R ALL post blinatumomab failure is poor with a median survival of 6.4 months. Inotuzumab ozogamicin is a good salvage therapy option allowing patients with refractory disease to proceed with allo-SCT that remains the only curative approach for these patients. Table 1. Clinical Characteristics of Patients with Blinatumomab Failure N=30 Parameter N (%)/Median [Range] Age (years) 29 [19-76] Sex (Male) 23 (77) Performance Status 1 [0-2] Cytogenetics Diploid 9 (30) t(4;11) 1 (3) Miscellaneous 15 (50) t(9;22) 1 (3) Insufficient Metaphase 4 (14) WBC at start (x 109/L) 2.75 [0.4-24] % PB blasts at start 8 [0-98] % BM Blasts at start 80 [10-98] WBC at failure (x 109/L) 3.4 [0-224] % BM Blasts at failure 69 [2-98] # Prior therapies, median 3 [1-6] # Blinatumomab courses 2 [1-5] Best response to blinatumomab CR 9 (30) CRi 3 (10) Median duration of response (months) 3 [1-8] Follow up, median (months) 6.8 [4.8-31] Disclosures Cortes: Teva: Research Funding; Novartis: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; BMS: Consultancy, Research Funding; BerGenBio AS: Research Funding; Ariad: Consultancy, Research Funding; Astellas: Consultancy, Research Funding; Ambit: Consultancy, Research Funding; Arog: Research Funding; Celator: Research Funding; Jenssen: Consultancy.

Yttrium 90 (90Y) Ibritumomab Tiuxetan (Zevalin®) Induces Long-Term Responses in Patients with Relapsed or Refractory Follicular Lymphoma (FL).

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2629-2629
Author(s):  
Russell J. Schilder ◽  
Thomas E. Witzig ◽  
Ian Flinn ◽  
Leo I. Gordon ◽  
Christos Emmanouilides ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
B Cell ◽  
Complete Response ◽  
Low Grade ◽  
Ibritumomab Tiuxetan ◽  
Bulky Disease ◽  
Prior Therapy ◽  
Yttrium 90

Abstract Background: Radioimmunotherapy (RIT) is an emerging clinical treatment option for patients with non-Hodgkin’s lymphoma (NHL). Yttrium 90 (90Y) ibritumomab tiuxetan (Zevalin®) RIT was approved by the FDA in February 2002 for the treatment of patients with relapsed or refractory low-grade, follicular, or transformed B-cell NHL, including patients with rituximab-refractory follicular NHL. In 4 registrational trials of 90Y ibritumomab tiuxetan conducted between 1996 and 1999, 211 patients with B-cell NHL were treated. Of these 211 patients, 153 patients (73%) had follicular lymphoma (FL). With ongoing follow-up, long-term durable responses have been observed, but until now have not been more fully characterized. Methods: Responding patients with time to progression (TTP) of ≥12 months were identified and characterized as long-term responding (LTR) patients. Results: In the 4 registrational trials, 78 of the 211 patients (37%) were identified as LTR patients. Characteristics of these LTR patients were as follows: median age 58 years (range, 24 to 80), 44% >60 years old, 55% male, 76% with follicular lymphoma, and 41% with lymphomatous marrow involvement. LTR patients had a median of 2 prior regimens (range, 1–9): 59% had ≥2 prior therapies, 33% had ≥3 prior therapies, and 37% had no response to their last prior therapy. Thirty percent of LTR patients had bulky disease (tumor size >5 cm) and 83% had stage III/IV disease. At the time of this analysis, the median duration of response (DR) and TTP for LTR patients were 28 months (range 11–80) and 29 months (range 12–82), respectively, with a median follow-up of 50 months (range 13–82). The median DR to the last prior therapy for LTR patients was 12 months. The complete response rate (confirmed [CR] and unconfirmed [CRu]) among LTR patients was 65%, and the median DR and TTP were 29 and 31 months, respectively, for CR/CRu patients. In ongoing responders the median DR is 52 months (range 48–80). Among the 153 patients with FL, 59 (39%) were identified as LTR patients. Compared to the overall LTR patients, LTR patients with FL had similar disease characteristics, DR, TTP, and CR/CRu rates. Conclusions: Ongoing follow-up indicates that 90Y ibritumomab tiuxetan frequently produces durable long-term responses (TTP ≥12 months) in patients with relapsed or refractory B-cell NHL. Failure to respond to the therapy immediately prior to treatment with 90Y ibritumomab tiuxetan does not appear to affect the ability to achieve long-term responses with 90Y ibritumomab tiuxetan. Durable long-term responses were achieved in 37% of all patients and 39% of patients with FL treated in 4 registrational trials of 90Y ibritumomab tiuxetan at 30 centers in the US. Of these LTR patients, a high proportion were >60 years old and had received ≥3 prior therapies.

Long Term Follow-Up and Retreatment of Patients with Low-Grade Lymphoproliferative Disorders (LPD) after 1 Year of Phamacokinetic (PK) Based Maintenance Therapy with Rituximab.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4479-4479
Author(s):  
Jennifer R. Duff ◽  
James W. Lynch
Keyword(s):  
Maintenance Therapy ◽  
Progression Free Survival ◽  
Complete Response ◽  
Subsequent Treatment ◽  
Entire Group ◽  
Published Data ◽  
Low Grade ◽  
Long Term Follow Up

Abstract Background: We previously published data from a PK based maintenance trial in patients with CD 20 positive LPD. The PK based schedule derived from that trial was 1 dose every 3 months and is currently being evaluated in a large randomized trial (ECOG 4402). There has been appropriate concern that offering maintenance therapy may select for tumor cells resistant to rituximab thereby compromising the chance of response if patients are retreated once relapsing after such therapy. We now present long term follow-up on patients with low grade LPD treated on that trial. We furthermore report the results of retreating 5 patients who initially responded but relapsed after one year of maintenance rituximab. Methods: Patients with CD20 positive LPD (except SLL/CLL) were treated with four weekly infusions of rituximab 375mg/m2. All patients without PD were then monitored for 1 year and received a single infusion of 375mg/m2 when the level fell below <25mcg/ml. Among 22 patients with low grade LPD 10 (45%) achieved a complete response and 5 (23%) a partial response for an overall response rate with 68%. With a minimal follow-up of 69 months, all but 2 patients have sufficient data available to evaluate their subsequent treatment and response. Results: Of the 22 patients, there were 18 with follicular lymphoma, 2 with lymphoplasmacytoid lymphoma and 1 each with MALT and NOS. The median progression free survival (PFS) for the entire group was 23 months, but for responders the PFS was 50 months. 6/22 (27%) remain in continuous complete remission with no further therapy with a median follow-up of 72.5 mo. (range 69–76). Nine patients who initially responded have subsequently relapsed and were treated at the discretion of the treating physician as follows: 2 received no treatment one of whom experienced a spontaneous CR lasting 59 months, one patient with an isolated CNS relapse received intrathecal and local radiotherapy and is currently in CR with no further therapy at 71mo, 1 patient died in PR of a presumed MI and 5 received retreatment with rituximab accompanied by 2 years of maintenance therapy given as 1 dose every 3 months. Of the 5 patients who were retreated with rituximab the outcomes are listed in table I. Conclusions: Individualized PK dosing for rituximab for 1 year yielded 27% prolonged DFS in patients with LG LPD. Although the numbers of patients treated are very small, 80% of those who responded to rituximab and subsequently relapsed retained sensitivity to rituximab and have had durable benefits, comparable to their first course. Future trials which evaluate the efficacy of limited duration maintenance strategies should continue follow-up of patients after progression to determine whether subsequent treatment with rituximab offers clinical benefit. Table I Patient # 1st PFS 2nd Response 2nd PFS 1 18mo CR 44mo+ 2 23mo NR NA 3 27mo CR 33mo 4 29mo CR 33mo+ 5 50mo PR 29mo+

scholarly journals Long Term Follow up of the Resort Study (E4402): A Randomized Phase III Study Comparing Two Different Rituximab Dosing Strategies for Low Tumor Burden Follicular Lymphoma

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 815-815
Author(s):  
Brad S. Kahl ◽  
Fangxin Hong ◽  
Christopher Peterson ◽  
Lode J. Swinnen ◽  
Thomas M. Habermann ◽  
...  
Keyword(s):  
Treatment Failure ◽  
Research Funding ◽  
Response Duration ◽  
Tumor Burden ◽  
Cytotoxic Therapy ◽  
Time To Treatment ◽  
Time To Treatment Failure ◽  
Long Term Follow Up

Abstract BACKGROUND: E4402 was a randomized phase III study comparing two different rituximab dosing strategies for patients with previously untreated, low tumor burden follicular lymphoma (FL). The primary endpoint was time to treatment failure. The initial publication (Kahl, JCO 2014) demonstrated that a retreatment strategy utilized less drug and produced comparable time to treatment failure compared to a maintenance strategy. Here we provide long term follow up results, focusing on response duration, time to first cytotoxic therapy, overall survival, and risk of histologic transformation. METHODS: Eligible patients had untreated, low tumor burden (GELF criteria) FL. Patients received R 375 mg/m 2 weekly x 4 and responders were randomized to maintenance rituximab (MR) (single dose R q 3 months) or retreatment rituximab (RR) (R weekly x 4 doses at disease progression). Each strategy was continued until treatment failure. The primary endpoint, time to treatment failure, was defined as progression within 6 months of last R, no response to R retreatment, initiation of alternative therapy, or inability to complete protocol therapy. Secondary endpoints included time to first cytotoxic therapy, quality of life and safety. The ECOG Data Monitoring Committee recommended release of study results at a planned interim analysis in September 2011 and patients and providers were notified of results. Time to treatment failure data collection halted with release of the results but limited data collection on time to first cytotoxic therapy, response duration, and risk of histologic transformation continued. INITITIAL RESULTS: From 11/03 to 9/08, 384 patients with FL were enrolled. Complete or partial response was achieved in 289 patients (71%), who were then randomized to MR (n=146) or RR (n=143). Demographic features were similar in the two arms: median age 59 years; ECOG PS 0-1 in all patients, and FLIPI low-risk (14.9 vs. 16.4%), intermediate-risk (46.3 vs. 42.9%) and high-risk (38.8 vs. 40.7%) for MR vs. RR, respectively. At initial publication, with a median follow-up of 3.8 years, the time to treatment failure was 3.9 years for MR vs. 3.6 years for RR (p=NS). LONG TERM FOLLOW UP RESULTS: Immunoglobulin levels and risks for serious infections/late complications in MR patients will be updated at the annual meeting. For the endpoint of time to first cytotoxic therapy, the median follow up is 8.7 years. At 7 years, 83% of MR and 63% of RR remained free from first cytotoxic therapy (HR 2.37; 95% CI 1.50 - 3.76) [Figure 1]. For the endpoint of response duration, the median follow up is 12.1 years. At 10 years, 66% of the MR patients remained in their 1 st remission compared to 30% of the RR patients who remained in their 1 st remission [Figure 2]. The median response duration for RR patients receiving a single 4-week course of rituximab was 3.25 years. There was no difference in the overall survival at 10 years, 84% for MR vs. 83% for RR. There was a trend towards a lower risk of histologic transformation for patients receiving MR (n = 4) compared to RR (n = 11) (p = 0.11). CONCLUSIONS: With long term follow up, the RESORT data indicates that in previously untreated, low tumor burden, follicular lymphoma, MR was superior to RR for delaying time to first cytotoxic therapy and for response duration, with a trend towards reducing the risk of histologic transformation. MR did not improve the overall survival. The original publication concluded that the time to treatment failure is similar between the two dosing strategies. Due to study design, time to treatment failure could not be analyzed in this long term follow up analysis. Compared to the historical benchmark of 3 years median time to first cytotoxic therapy when watch and wait is utilized, single agent rituximab, administered by either dosing strategy, was highly effective at delaying the time to first cytotoxic therapy. Figure 1 Figure 1. Disclosures Kahl: AbbVie, Adaptive, ADCT, AstraZeneca, Bayer, BeiGene, Bristol-Myers Squibb, Celgene, Genentech, Incyte, Janssen, Karyopharm, Kite, MEI, Pharmacyclics, Roche, TG Therapeutics, and Teva: Consultancy; AbbVie, Acerta, ADCT, AstraZeneca, BeiGene, Genentech: Research Funding. Habermann: Incyte: Other: Scientific Advisory Board; Tess Therapeutics: Other: Data Monitoring Committee; Seagen: Other: Data Monitoring Committee; Morphosys: Other: Scientific Advisory Board; Loxo Oncology: Other: Scientific Advisory Board; Eli Lilly & Co.,: Other: Scientific Advisor. Schuster: Abbvie: Consultancy, Research Funding; Acerta Pharma: Consultancy; AstraZeneca: Consultancy; Adaptive Biotechnologies: Research Funding; BeiGene: Consultancy; Celgene: Consultancy, Honoraria, Research Funding; DTRM: Research Funding; Genetech: Consultancy, Research Funding; Roche: Consultancy, Research Funding; Incyte: Research Funding; Juno Theraputics: Consultancy, Research Funding; Loxo Oncology: Consultancy; Merck: Research Funding; Nordic Nanovector: Consultancy; Novartis: Consultancy, Honoraria, Patents & Royalties, Research Funding; Pharmaclcyclics: Research Funding; Tessa Theraputics: Consultancy; TG Theraputics: Research Funding. Fenske: TG Therapeutics: Consultancy, Speakers Bureau; Servier Pharmaceuticals: Consultancy; Seattle Genetics: Speakers Bureau; Sanofi: Speakers Bureau; Pharmacyclics: Consultancy; MorphoSys: Consultancy; Kite (Gilead): Speakers Bureau; KaryoPharm: Consultancy; CSL Therapeutics: Consultancy; Bristol-Myers Squibb: Speakers Bureau; Biogen: Consultancy; Beigene: Consultancy; AstraZeneca: Speakers Bureau; ADC Therapeutics: Consultancy; Adaptive Biotechnologies: Consultancy; AbbVie: Consultancy.

Long Term Follow-Up of Patients with Immune Thrombocytopenic Purpura (ITP) Whose Initial Response to Rituximab Lasted a Minimum of 1 Year.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 479-479 ◽  
Author(s):  
Vivek Patel ◽  
Nino Mihatov ◽  
Nichola Cooper ◽  
Roberto Stasi ◽  
Susanna Cunningham-Rundles ◽  
...  
Keyword(s):  
Platelet Count ◽  
B Cell ◽  
Treatment Algorithm ◽  
Specific Treatment ◽  
Initial Response ◽  
Chronic Itp ◽  
Duration Of Response ◽  
Long Term Follow Up

Abstract Objective: Rituximab was licensed (1997) to treat B-cell lymphomas. As a consequence of its B-cell depleting effect, Rituxmab has been widely used in autoimmune conditions including ITP. This study assessed the long term efficacy of Rituximab in patients with chronic ITP. Methods: All patients with responses lasting more than 1 year (yr) to Rituximab treatment were included in this IRB approved study to determine the duration of response to Rituximab. Forty six patients fulfilled these criteria; thus far complete data are available for 31. The median follow up (f/u) was 2 3/4 yrs. At onset of Rituximab treatment, the 31 patients had platelet counts &lt;30 x 10 9/l, had received two or more previous ITP treatments, and 14 (44%) had undergone splenectomy. The median age and duration of ITP were 32 yrs (range 12–65) and 1 3/4 yrs respectively. The patients received Rituximab at 375 mg/m2 weekly for 4 weeks. The 15 patients for which data are not available had similar characteristics. Results: The figure outlines what happens more than one yr from Rituximab treatment for those patients whose response lasted &gt; 1 yr. Fourteen of the 31 patients have relapsed within the f/u period giving a 5 yr response rate of 55%. Eleven of the 14 relapsers did so within 2 1/2 yrs of their first infusion whereas 14 of the 17 patients with ongoing responses had f/u &gt; 2 1/2 yrs. The data suggest that patients whose response is &gt; 2 1/2 yrs have a low likelihood of relapse before 5 years. While duration of ITP prior to Rituximab treatment was significantly shorter (p&lt; 0.001) for patients responding over 3 years (median=39 weeks) than it was for those responding between 1 and 3 years (median=176 weeks), no specific duration of ITP prior to which Rituximab should be instituted was evident. None of age, sex, time to a platelet count &gt; 30 x 109/l, and splenectomy status predicted duration of response to Rituximab. Out of the original 31 responders, there were 25 complete responses (CR: platelet count &gt;150 x 109/l) and 6 partial responses (PR: platelet count 30–150 x 109/l). Fifteen (60%) of the CRs and 2 of the PRs (33%) remain in lasting remission (p=NS). Characteristics such as median age, duration of ITP, gender, splenectomy status, and median duration of response were similar for both PRs and CRs. Data on toxicity are less well-developed; no serious infections, malignancies, or other major toxicities were seen in this group of patients. In conclusion, several studies including our own (Cooper Brit J Haem 2004) demonstrated that approximately 1/3 of Rituximab treated patients would have a duration of response lasting &gt; 1 yr. Among this 1/3, now with considerable additional f/u, lasting responses to Rituximab were seen in more than half. Taken together, these findings imply that responses &gt; 2 1/2 yrs in duration would occur in approximately 1/6 of the starting population of Rituximab-treated patients with chronic ITP with little further relapse in the subsequent 2 1/2 yrs. While informing the long term response to Rituximab, this study cannot yet provide a specific treatment algorithm. Duration of Response to Rituximab in 31 Patients with Chronic ITP with a Response Greater than 1 Year Duration of Response to Rituximab in 31 Patients with Chronic ITP with a Response Greater than 1 Year

Long term follow up after treatment of hairy cell leukemia with 2-CdA

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 16518-16518
Author(s):  
M. Ramzi ◽  
M. Haghshenas
Keyword(s):  
Partial Response ◽  
Hairy Cell Leukemia ◽  
Complete Response ◽  
Second Malignancy ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Duration Of Response ◽  
Long Term Follow Up

16518 Background: Hairy cell leukemia (HCL) is a chronic B cell disorder that follows an indolent but progressive course. The ability of new purine analogue deoxyadenosine to induce long lasting complete remission in patients with hairy cell leukemia has revolutionized the treatment of this disease. We report the long term outcomes of patients with HCL treated in Shiraz, in south of Iran,with this drug. Methods: Between October 1993 till April 2004, 79 patients with classic symptomatic hairy cell leukemia were treated with 2-cholorodeoxy adenosine (2-CdA) with dose of 0.1 mg/kg of body weight per day by continuous intravenous infusion for 7 days. Results: sixty nine (87%) of patients achieved an initial complete response and 10 (12.6) a partial response with an overall median duration of response follow up of 78 months. Five patients had relapsed at a median of 43 months. All of 5 patients after relapse treated with second courses of 2-CdA, 4 (80%) achieved second complete responses and one (20%) partial response. In our study we had not any case of second malignancy after treatment with 2-CdA with median follow up of 82.5 months. Conclusion: This study confirms single course of 2-CdA induced long lasting complete response in the vast majority of patients. Relapse rate for complete responders were low. Patients who relapse can be successfully retreated with this drug, so we conclude 2-CdA had high efficacy and a favorable acute and long term toxicity profile in our patients in south of Iran, without any increase in risk of second malignancy. No significant financial relationships to disclose.

scholarly journals The Long-Term Follow-Up of Patients with Cystine Stones: A Single-Center Experience for 13 Years

2021 ◽  
Vol 10 (7) ◽  
pp. 1336
Author(s):  
Toshifumi Takahashi ◽  
Shinya Somiya ◽  
Katsuhiro Ito ◽  
Toru Kanno ◽  
Yoshihito Higashi ◽  
...  
Keyword(s):  
Surgical Intervention ◽  
Median Number ◽  
Small Sample ◽  
Age At Diagnosis ◽  
Surgical Interventions ◽  
Significant Difference ◽  
Long Term Follow Up ◽  
Cystine Stones

Introduction: Cystine stone development is relatively uncommon among patients with urolithiasis, and most studies have reported only on small sample sizes and short follow-up periods. We evaluated clinical courses and treatment outcomes of patients with cystine stones with long-term follow-up at our center. Methods: We retrospectively analyzed 22 patients diagnosed with cystine stones between January 1989 and May 2019. Results: The median follow-up was 160 (range 6–340) months, and the median patient age at diagnosis was 46 (range 12–82) years. All patients underwent surgical interventions at the first visit (4 extracorporeal shockwave lithotripsy, 5 ureteroscopy, and 13 percutaneous nephrolithotripsy). The median number of stone events and surgical interventions per year was 0.45 (range 0–2.6) and 0.19 (range 0–1.3) after initial surgical intervention. The median time to stone events and surgical intervention was 2 years and 3.25 years, respectively. There was a significant difference in time to stone events and second surgical intervention when patients were divided at 50 years of age at diagnosis (p = 0.02, 0.04, respectively). Conclusions: Only age at a diagnosis under 50 was significantly associated with recurrent stone events and intervention. Adequate follow-up and treatment are needed to manage patients with cystine stones safely.

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