Single Treatment with Rituximab Monotherapy for Low-Tumor Burden Follicular Lymphoma (FL): Survival Analyses with Extended Follow-Up (F/Up) of 7 Years.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 486-486 ◽  
Author(s):  
Philippe Colombat ◽  
Nicole Brousse ◽  
Franck Morschhauser ◽  
Patricia Franchi-Rezgui ◽  
Pierre Soubeyran ◽  
...  
Keyword(s):  
Sleep Apnea Syndrome ◽  
Response Duration ◽  
Final Analysis ◽  
Initial Response ◽  
Tumor Burden ◽  
Best Response ◽  
Duration Of Response ◽  
Study Population

Abstract As previously reported (Colombat, Blood2001;97:101), rituximab (4 weekly doses of 375mg/m²) can lead to high response rates (RR) and prolonged remissions with minimal toxicity as 1st line therapy for low tumor burden FL. We report the final analysis of a trial evaluating long term efficacy and safety of rituximab in untreated low tumor burden FL (GELF criteria). 49 patients (pts) were included in the initial trial (median age 52 yrs), 2 refused consent for the extended F/Up period, and 1 pt died at M12. Molecular bcl2-JH rearrangement was assessed throughout the study. The median F/up was 83.8 mths. Overall best RR, complete/unconfirmed RR and partial RR at D78 were 74%, 50% and 24% respectively. Median PFS was 23.5 mths for the study population. Median duration of response (34 responders at D78, i.e 6 weeks after the last rituximab dose) was 28.6 mths, but response was still maintained without any further treatment in 11 pts after 5 years (24%) and in 7 pts after 7 years (15%). 31/46 pts were bcl2 positive in blood and/or marrow samples before rituximab: 11 (35%) became negative at D50, and 20 remained positive (65%). Median PFS was 37 mths for bcl2-negative pts at D50, and 12 mths for patients remaining positive (p=0.018 Log-rank). Of the 7 pts with sustained response after 7 years, 5 were bcl2 positive at D0, 2/5 became negative at D50, and 5/5 were still negative at M84. At year 7, 4/46 pts have died (1 from myelodysplasia, 3 from NHL), 35/42 have progressed, and 7 have never progressed without any other treatment than the initial rituximab therapy. Time to progression was significantly longer in the bcl2-negative population at D50 (p= 0.018, Log-rank). Duration of response was not correlated with bcl2 status at D50, but was associated with ‘Best response CR/Cru’ (p=0.007 Log-rank). Long-term tolerance was good, with only 13 SAE observed in 13 pts during the additional 4 years of F/Up (4 surgeries for non NHL-related pathologies, 1 node biopsy, 1 sleep apnea syndrome, 1 ischemic cardiopathy, 2 deaths from NHL, 1 depression, 1 pneumonia, 1 erysipela, 1 bronchitis). This long-term update confirms that a single 4-dose rituximab treatment yields durable benefits without the toxicity of chemotherapy for pts with low burden FL : Median PFS of 23.5 mths for the cohort, 28.6 mths for responders and 37 mths for pts turning bcl2-negative at D50, 15% of pts have maintained their response after 7 years, (2bis) the quality (CR/Cru) of the initial response was associated with a longer response duration high overall survival is observed with 4 deaths/46 pts (8.6%).

A Combination of Rituxan, Cyclophosphamide and Dexamethasone (RCD) Results in Long-Lasting Responses in Autoimmune Anemia and Thrombocytopenia in CLL Patients: A Single Institution Study.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2832-2832
Author(s):  
Matthew S. Kaufman ◽  
Yehuda Z. Lebowicz ◽  
Nancy Driscoll ◽  
Christina Johnson ◽  
Dale Janson ◽  
...  
Keyword(s):  
Response Duration ◽  
Initial Response ◽  
Tumor Burden ◽  
Post Treatment ◽  
Lymphocytic Leukemia ◽  
First Episode ◽  
Available N ◽  
Duration Of Response ◽  
Autoimmune Processes

Abstract Coombs positive hemolytic anemia (AIHA) and idiopathic thrombocytopenic purpura (ITP) are well-known complications of chronic lymphocytic leukemia(CLL). Both are autoimmune phenomena thought to be byproducts of the immune system dysregulation manifested in patients with CLL. Rituxan, cyclophosphamide and dexamethasone(RCD) are known to effectively target lymphocytes and inhibit autoimmune processes. We present our data analyzing 18 CLL patients with one or both of these autoimmune processes treated with the RCD regimen between 1998 and 3/2006. These patients consisted of 15 with AIHA alone, 2 with both AIHA and ITP and one with ITP alone. The RCD cycle consisted of rituximab 375mg/m2 iv infusion given on day 1, cyclophosphamide 750–1000mg/m2 iv (depending on CLL tumor burden) on day 2, and dexamethasone 12 mg iv on days 1 and 2, and orally days 3 through 7. These cycles were repeated at intervals of 3–4 weeks, depending upon recovery of blood counts. All 18 patients responded to treatment in terms of hgb, platelets or both. For the first episodes of AIHA (n=17) mean starting hgb was 8.1g/dL (range 4.0–12.1) and mean post-treatment hgb was 13.2 g/dL(range 10.0–15.4)(Table 1). The three patients with ITP had a platelet increase from nadirs of 1,000, 1,000 and 14,000 to 408,000, 161,000 and 135,000, respectively. Mean duration of initial response was 22 months (range 6–41). Nine patients relapsed and were retreated with RCD. Again, all 9 responded, and had a mean increase in hgb of 5.1g/dL (range 1.4–7.7) with a mean duration of second response of 16 months(range 3–33). Overall, median survival from initiation of RCD was 70 months (95% CI; 46 to an upper limit not-yet determinable, with follow-up to 8/2006). Of 8 patients with post-treatment Coombs data available for the first episode of AIHA, 4 (50%) converted to Coombs negativity (Table2) and had a mean duration of response of 23.0 months (range 12–41) vs 8.8 months for those who did not convert(range 6–11). In all AIHA episodes (including repeat episodes) with post-treatment Coombs data available (n=18), 6 of 18 (33%) converted to Coombs negativity. The mean duration of response was 19.8 months (range 6–41) for all episodes with conversion to Coombs negativity, vs 7.0 months for those without(range 3–12). This finding that Coombs conversion portends a longer duration of response suggests treatment goals for AIHA should be a conversion to Coombs negative, and not stopped with recovery of hgb. Table 1. Hemoglobin response to RCD N Mean Std Deviation Min Hgb Max Hgb at start episode 1 17 8.1 g/dL 2.1 4.0 g/dL 12.1 g/dL Hgb at end episode 1 17 13.2 g/dL 1.4 10.0 g/dL 15.4 g/dL Hgb delta episode 1 17 5.1 g/dL 2.3 1.7 g/dL 10.2 g/dL Hgb at start episode 2 9 8.4 g/dL 2.3 5.3 g/dL 12.2 g/dL Hgb at end episode 2 9 13.5 g/dL 1.4 12.3 g/dL 16.6 g/dL Hgb delta episode 2 9 5.1 g/dL 2.1 1.4 g/dL 7.7 g/dL Table 2. Post-treatment Coombs status and response duration N Mean duration of response (in months) Post-treatment Coombs negativity in episode 1 4 22.2 (range 12-41) Post-treatment Coombs positivity in episode 1 4 8.8 (range 6-11) Post-treatment Coombs negativity in all episodes 6 19.8 (range 6-41) Post-treatment Coombs positivity in all episodes 12 7.1 (range 3-12)

Azacytidine in the Management of Myelodysplastic Syndrome: A Single Institutional Retrospective Review of Responses and Tolerability.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4851-4851
Author(s):  
David L. Grinblatt ◽  
Seema Bavisi ◽  
Jessica Lawton ◽  
Lynne S. Kaminer
Keyword(s):  
Myelodysplastic Syndrome ◽  
Response Duration ◽  
Complete Response ◽  
Refractory Anemia ◽  
Treatment Frequency ◽  
Best Response ◽  
Complete Hematologic Response ◽  
Duration Of Response ◽  
Neutropenic Patients

Abstract Twenty two patients (pts) with primary or therapy-related MDS were treated with 5-azayctidine (AZA) at the Kellogg Cancer Care Centers (KCCC) from July 2004–May 2006. We retrospectively reviewed all consecutive patients with myelodysplastic syndrome treated at the KCCC who received this agent. Charts were reviewed for response, time to response, duration of response and rate of hospitalization with complications of therapy or disease during AZA therapy. Treated patients had Refractory Anemia with Excess Blasts-type 1 (RAEB-1, n=6), RAEB type-2 (RAEB-2, n=3), Chronic Myelomonocytic Leukemia (CMMoL, n=4) or Refractory anemia (RA, n=6). Median age at study entry was 80 yrs (range, 58–95). Patients were treated with azacytidine 75mg/m2 daily for seven consecutive days or five days followed by a two day break and an additional two days of treatment. Patients were treated until best response and treatment frequency was decreased to every 6–8 weeks once a response had occurred. Responses were as follows: Complete response (CR) with normalization of cytopenias, marrow dysplasia and blasts (as defined in IWG criteria by Cheson et al) occurred in 2 pts (9%). Complete hematologic response (CHR) meeting all of the peripheral blood criteria but without a confirmation bone marrow performed was noted in 4 pts (18%) while hematologic improvement (HE) major (>2 gm rise in Hgb) occurred in 1 pt (5%) and HE minor (1–2 gm rise in Hgb or 50% decrease in RBC requirements) occurred in 2 pts (9%). Thus, a response using the IWG criteria was seen in 9/22 pts yielding an overall response rate of 41%. The median time to response was 3 cycles (range, 1–4). The median duration of response was 8 months (range, 3–18+). Responses are ongoing in 4/9 of the responders. One of the complete response patients had a complex karyotype (5q-, 7q-, del (18p)) that was not present on follow-up marrow after response was noted. Though treatment related cytopenias did occur frequently in the first two cycles of therapy, there were no treatment related hospitalizations for neutropenic patients in this consecutive cohort of patients and no deaths due to therapy. Azacytidine is a well tolerated agent with responses occurring with a significant rate and duration in MDS.

scholarly journals Acromegaly at diagnosis in 3173 patients from the Liège Acromegaly Survey (LAS) Database

2017 ◽  
Vol 24 (10) ◽  
pp. 505-518 ◽  
Author(s):  
Patrick Petrossians ◽  
Adrian F Daly ◽  
Emil Natchev ◽  
Luigi Maione ◽  
Karin Blijdorp ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Thyroid Nodules ◽  
Sleep Apnea Syndrome ◽  
Multiple Treatment ◽  
Long Term Follow Up ◽  
Study Population ◽  
Apnea Syndrome ◽  
Over Time

Acromegaly is a rare disorder caused by chronic growth hormone (GH) hypersecretion. While diagnostic and therapeutic methods have advanced, little information exists on trends in acromegaly characteristics over time. The Liège Acromegaly Survey (LAS) Database, a relational database, is designed to assess the profile of acromegaly patients at diagnosis and during long-term follow-up at multiple treatment centers. The following results were obtained at diagnosis. The study population consisted of 3173 acromegaly patients from ten countries; 54.5% were female. Males were significantly younger at diagnosis than females (43.5 vs 46.4 years; P < 0.001). The median delay from first symptoms to diagnosis was 2 years longer in females (P = 0.015). Ages at diagnosis and first symptoms increased significantly over time (P < 0.001). Tumors were larger in males than females (P < 0.001); tumor size and invasion were inversely related to patient age (P < 0.001). Random GH at diagnosis correlated with nadir GH levels during OGTT (P < 0.001). GH was inversely related to age in both sexes (P < 0.001). Diabetes mellitus was present in 27.5%, hypertension in 28.8%, sleep apnea syndrome in 25.5% and cardiac hypertrophy in 15.5%. Serious cardiovascular outcomes like stroke, heart failure and myocardial infarction were present in <5% at diagnosis. Erythrocyte levels were increased and correlated with IGF-1 values. Thyroid nodules were frequent (34.0%); 820 patients had colonoscopy at diagnosis and 13% had polyps. Osteoporosis was present at diagnosis in 12.3% and 0.6–4.4% had experienced a fracture. In conclusion, this study of >3100 patients is the largest international acromegaly database and shows clinically relevant trends in the characteristics of acromegaly at diagnosis.

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.

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.

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

scholarly journals Italian Real Life Experience with Brentuximab Vedotin: Results of a National Observational Study on Relapsed/Refractory Anaplastic Large Cell Lymphoma

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3007-3007
Author(s):  
Cinzia Pellegrini ◽  
Luigi Rigacci ◽  
Caterina Patti ◽  
Guido Gini ◽  
Donato Mannina ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Response Rate ◽  
Real Life ◽  
Large Cell ◽  
Brentuximab Vedotin ◽  
Advisory Committees ◽  
Best Response ◽  
Duration Of Response

Abstract From November 2012 to July 2014, brentuximab vedotin (BV) was available in Italy for patients with relapsed systemic anaplastic large cell lymphoma (ALCL) outside a clinical trial context based on a local disposition of the Italian Drug Agency (AIFA) issued according to a national law (Law 648/96: "medicinal products that are provided free of charge on the national health service"). A large Italian observational retrospective study was conducted on the use of BV in the everyday clinical practice to check if clinical trial results are confirmed even in a real life context. Primary endpoint was the best response; secondary endpoints were the overall response rate at the end of the treatment, duration of response, survival and the safety profile. BV was infused intravenously at the dose of 1.8 mg/kg every 3 weeks for a maximum of 16 cycles. A total of 40 ALCL (18 anaplastic lymphoma kinase [ALK] negative and 22 ALK-positive status) patients were treated with BV in 40 Hematology Centers. All patients had histologically documented CD30+ ALCL; 16 (40%) had relapsed and 24 (60%) had refractory disease. Patients were heavily pretreated with a median of 2 previous therapies (including autologous transplant in the 32.5% of cases). Best response was observed after a median of 4 cycles in 31 patients (77.5%): 19 (47.5%) patients obtained a complete response (CR) and 12 (30%) achieved a partial response (PR); overall response rate at the end of the treatment was 62.5% (18 CR and 7 PR). The best response rate was higher in the elderly subset (>60 years): 9 (64.2%) CR and 3 (21.4%) PR, achieving a total of 85.6%. At the latest follow up 15/18 patients are still in CR (3 with consolidative procedure). Global progression free survival was 39.1% at 29 months and disease free survival 54% at 23.9 months (median not reached). Median duration of response was 12 months (range 9-24 months). We identified 5 long term responders (patients with a response ≥ 12 months), all were still in CR at the latest follow up (1 underwent allogeneic transplant). Particularly, all the long term responders were aged <30 years at first BV infusion. All patients were included in the safety profile for the analysis; in general, the treatment was well tolerated even in this real life context and the toxicity profile was closely similar to the previously published data; no death has been linked to BV toxicity. Toxicity was primarily neurological and rarely so serious as to require treatment reduction or interruption; furthermore, neurological toxicity always reversed completely after end of treatment. No long-term toxicity was assessed during the follow-up period, even in patients later subjected to transplant consolidation. BV induces clinical responses quite rapidly, i.e. within the first 4 cycles in most responders, thus permitting the timely application of the transplantation phase. Furthermore, BV displays a favorable toxicity profile, without overlapping toxicities with most of the agents employed in high-dose conditioning regimens. For patients ineligible for transplant or for who transplant failed, BV may represent a feasible effective therapeutic option in everyday clinical practice. Disclosures Rusconi: Takeda: Consultancy; Teva: Consultancy, Other: Congress attendance; Janssen: Consultancy, Other: Congress attendance. Spina:Mundipharma: Membership on an entity's Board of Directors or advisory committees, Other: Speaker Fee; Teva Pharmaceuticals Industries: Membership on an entity's Board of Directors or advisory committees, Other: Speaker Fee. Zinzani:Abbvie: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; MorphoSys: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Celegene: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees.

Long-term outcomes in patients (pts) with ipilimumab (ipi)-naive advanced melanoma in the phase 3 KEYNOTE-006 study who completed pembrolizumab (pembro) treatment.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 9504-9504 ◽  
Author(s):  
Caroline Robert ◽  
Georgina V. Long ◽  
Jacob Schachter ◽  
Ana Arance ◽  
Jean Jacques Grob ◽  
...  
Keyword(s):  
Tumor Imaging ◽  
Final Analysis ◽  
Complete Response ◽  
Advanced Melanoma ◽  
Long Term Outcomes ◽  
Duration Of Treatment ◽  
Phase 3 ◽  
Best Response

9504 Background: Pembro demonstrated superior PFS and OS vs ipi in ipi-naive pts with advanced melanoma in the phase 3 KEYNOTE-006 study (NCT01866319). Here, we present long-term outcomes for all pts and in those pts who completed pembro therapy. Methods: Eligible pts (N = 834) were randomized 1:1:1 to pembro 10 mg/kg Q2W, pembro 10 mg/kg Q3W, or ipi 3 mg/kg Q3W for 4 doses. Treatment was continued for 2 yr (pembro only) or until disease progression, intolerable toxicity, or pt/investigator decision to discontinue. Per protocol, pts could interrupt pembro for ≤12 wk before discontinuation was required. Tumor imaging was performed at wk 12, then every 6 wk up to wk 48 and every 12 wk thereafter. After the prespecified final analysis, response assessments were per immune-related response criteria (irRC) by investigator review. Results: As of the data cutoff (Nov 3, 2016), median follow-up in the total population was 33.9 mo (range, 32.1-37.6). 33-mo OS rates were 50% in the pooled pembro arms (n = 556) and 39% in the ipi arm (n = 278); 33-mo PFS rates were 31% and 14%. ORR was 42% and 16%. Median duration of response was not reached for pembro (range 1.0+ to 33.8+ mo) or ipi (1.1+ to 34.8+ mo); 46 (68%) pembro-treated pts and 7 (58%) ipi-treated pts had a response lasting ≥30 mo. Among the 104/556 (19%) pts who completed pembro, median exposure to pembro was 24.0 mo (range 22.1-25.9). After a median follow-up of 9.0 mo after completion of pembro, 102 (98%) pts were alive. Responses were durable in pts who completed pembro; 9.7 mo after completion of pembro, estimated PFS (95% CI) was 91% (80-96) in all 104 pts, 95% (69-99) in pts with complete response (n = 24), 91% (74-97) in pts with partial response (n = 68), and 83% (48-96) in pts with stable disease (n = 12). Conclusions: Pembro provides durable efficacy after stopping the protocol-specified duration of treatment in pts with ipi-naive advanced melanoma in KEYNOTE-006. The estimated risk for progression or death nearly 10 mo after completing pembro is 9% and does not appear to differ by best response to pembro. Clinical trial information: NCT01866319.

Final analysis of the CheckMate 025 trial comparing nivolumab (NIVO) versus everolimus (EVE) with >5 years of follow-up in patients with advanced renal cell carcinoma (aRCC).

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 617-617 ◽  
Author(s):  
Robert J. Motzer ◽  
Scott S. Tykodi ◽  
Bernard Escudier ◽  
Stephane Oudard ◽  
Hans J. Hammers ◽  
...  
Keyword(s):  
Objective Response ◽  
Progression Free Survival ◽  
Final Analysis ◽  
Primary Analysis ◽  
Duration Of Response ◽  
Long Term Follow Up ◽  
Previously Treated ◽  
Grade 3

617 Background: CheckMate 025 demonstrated superior overall survival (OS) in previously treated patients (pts) with aRCC, with improved safety and tolerability in the NIVO arm compared with EVE. The primary analysis was based on 14-months minimum follow-up. Here, we report an updated, final analysis with an extended minimum follow-up of 64 months. Methods: Previously treated pts with predominantly clear cell aRCC were randomized (1:1) to NIVO 3 mg/kg IV every 2 weeks or EVE 10 mg orally once daily until progression or unacceptable toxicity. The primary endpoint was OS. Secondary endpoints included objective response rate (ORR), progression-free survival (PFS), and safety. Confirmed ORR and PFS were per investigator (inv) using RECIST v1.1. Results: Overall, 410 vs 411 pts were randomized to NIVO vs EVE, respectively. OS benefit was maintained and PFS favored NIVO vs EVE with long-term follow-up (HR 0.84 (95% CI 0.72–0.99). (Table) ORR was higher (23% vs 4%) with NIVO vs EVE and median duration of response (DOR) was longer (18.2 vs 14.0 months). Ongoing response was observed in 28% vs 18% of pts with NIVO vs EVE. Most pts received subsequent systemic anticancer therapy: 276 pts in the NIVO arm (67%; most commonly EVE [35%] or axitinib [33%]) and 296 pts in the EVE arm (72%; most commonly axitinib [41%] or NIVO [26%]). No new safety signals or treatment-related deaths emerged with long-term follow-up in either arm. More pts in the EVE arm (37%) experienced a grade 3/4 treatment-related AE compared with pts in the NIVO arm (21%). Conclusions: At >5-years minimum follow-up, response rates and survival remain superior with NIVO vs EVE, and 28% of responses to NIVO are ongoing. Long-term follow-up highlights the efficacy and safety of NIVO monotherapy in pts with aRCC. Clinical trial information: NCT01668784. [Table: see text]

scholarly journals Minimum 10-Year Clinical Outcome of Lateral Collagen Meniscal Implants for the Replacement of Partial Lateral Meniscal Defects: Further Results From a Prospective Multicenter Study

2021 ◽  
Vol 9 (5) ◽  
pp. 232596712199491
Author(s):  
Alberto Grassi ◽  
Gian Andrea Lucidi ◽  
Giuseppe Filardo ◽  
Piero Agostinone ◽  
Luca Macchiarola ◽  
...  
Keyword(s):  
Survival Rate ◽  
Case Series ◽  
Final Analysis ◽  
Activity Level ◽  
Long Term Results ◽  
Level Of Evidence ◽  
Unicompartmental Knee Arthroplasties ◽  
Tegner Score

Background: The collagen meniscal implant (CMI) is a biologic scaffold aimed at replacing partial meniscal defects. The long-term results of lateral meniscal replacement have never been investigated. Purpose: To document the clinical outcomes and failures of lateral CMI implantation for partial lateral meniscal defect at a minimum 10-year follow-up. Study Design: Case series; Level of evidence, 4, Methods: This study included 24 consecutive patients who underwent lateral CMI implantation for partial lateral meniscal defects between April 2006 and September 2009 and who were part of a previous study with a 2-year follow-up. Outcome measures at the latest follow-up included the Lysholm score, Knee injury and Osteoarthritis Outcome Score, visual analog scale (VAS) for pain, Tegner activity level, and EuroQol 5-Dimensions score. Data regarding complications and failures were collected, and patients were asked about their satisfaction with the procedure. Results: Included in the final analysis were 19 patients (16 male, 3 female) with a mean age at surgery of 37.1 ± 12.6 years and a mean follow-up of 12.4 ± 1.5 years (range, 10-14 years). Five failures (26%) were reported: 1 CMI removal because of implant breakage and 4 joint replacements (2 unicompartmental knee arthroplasties and 2 total knee arthroplasties). The implant survival rate was 96% at 2 years, 85% at 5 years, 85% at 10 years, 77% at 12 years, and 64% at 14 years. Lysholm scores at the final follow-up were rated as “excellent” in 36% (5 of 14 nonfailures), “good” in 43% (6 of 14), and “fair” in 21% (3 of 14). The VAS score was 3.1 ± 3.1, with only 16% (3 of 19 patients) reporting that they were pain-free; the median Tegner score was 3 (interquartile range, 2-5). All clinical scores decreased from the 2-year follow-up; however, with the exception of the Tegner score, they remained significantly higher compared with the preoperative status. Overall, 79% of patients were willing to undergo the same procedure. Conclusion: Lateral CMI implantation for partial lateral meniscal defects provided good long-term results, with a 10-year survival rate of 85% and a 14-year survival rate of 64%. At the final follow-up, 58% of the patients had “good” or “excellent” Lysholm scores. However, there was a general decrease in outcome scores between the short- and the long-term follow-up.

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