scholarly journals Efficacy of Standard Dose R-CHOP Alternating with R-HiDAC Followed By ASCT As Initial Therapy of Mantle Cell Lymphoma: Cleveland Clinic Experience

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1730-1730
Author(s):  
Danyu Sun ◽  
Brian T. Hill ◽  
Lisa Rybicki ◽  
Basel Rouphail ◽  
Robert M Dean ◽  
...  
Keyword(s):  
Standard Dose ◽  
Cleveland Clinic ◽  
High Dose ◽  
First Line ◽  
Treatment Groups ◽  
First Line Therapy ◽  
Mantle Cell ◽  
Group A ◽  
Group B

Abstract Introduction: A common approach to initial treatment for young, fit patients (pts) with mantle cell lymphoma (MCL) is induction chemoimmunotherapy followed by high dose chemotherapy with autologous stem cell support (ASCT). Induction regimens with modifications of R-CHOP (rituximab-cyclophosphamide-doxorubicin-vincristine-prednisone) and/or incorporation of high dose cytarabine (HiDAC) appear more effective than RCHOP alone, as in R-HyperCVAD/MA (cyclophosphamide-vincristine-doxorubicin-dexamethasone alternating with methotrexate-cytarabine, MDACC), R-CHOP alternating with R-DHAP (rituximab-dexamethasone-cytarabine-cisplatin, European MCL Network) and dose intensified R-CHOP alternating with HiDAC followed by ASCT (Nordic Lymphoma Group). At the Cleveland Clinic, in 2010 we adopted as our standard induction regimen a modification of the Nordic protocol, using standard dose R-CHOP alternating with R-HiDAC for 3 cycles each or, for pts who had already been treated with R-CHOP x 6 cycles prior to referral for ASCT, an additional 2 R-HiDAC. Here we report analysis of our institutional experience with this regimen. We use as historical comparison pts with MCL who underwent ASCT at our institution following R-HyperCVAD/MA or R-CHOP. Method: We retrospectively analyzed the outcome of 87 MCL pts who received first line therapy including ASCT at Cleveland Clinic from Aug 1999 - Apr 2014. Pt characteristics, treatment regimens and biological markers were evaluated with regard to overall survival (OS) and relapse free survival (RFS). Pts were grouped according to induction chemotherapy: Group A (HyperCVAD/MA x4 cycles), Group B (R-CHOP x 6 cycles), and Group C (R-CHOP alternating with R-HiDAC for 6 total cycles or R-CHOP x 6 cycles followed by HiDAC x 2 cycles). All pts received ASCT consolidation therapy with high dose busulfan, cyclophosphamide, and etoposide. OS and RFS were estimated using the Kaplan-Meier method and compared among groups using the log-rank test. Cox proportional hazards analysis was used to identify univariable prognostic factors for OS and RFS. Results: The median age of the entire cohort was 59 years (range: 41-73), with male predominance (74%). All pts had ECOG performance score ≤1, MIPI low/intermediate/high scores were 57%/30%/13%. Complete remission prior to ASCT was achieved in 76% of pts. Pt characteristics, including MIPI scores, were evenly distributed among three treatment groups except for: (1) age (median age at diagnosis Group A=53 yr, Group B=62 yr, and Group C=57 yr, P<0.001) (2) more blastoid subtype in Group A (19%) while Group C had no blastoid subtypes of MCL (0%, P=0.03); and (3) higher proportion of patients in Group C with comorbidities (85.7%, p=0.003). With a median follow-up of 26.6 months, 2 year OS rate (Fig. 1) was 95.2%, 94.7% and 100% in groups A, B and C respectively; 2 year RFS rate (Fig. 2) of 85.7%, 73.7% and 93.3% respectively. In univariate analysis, blastoid subtype (HR=5.37, 95% CI 1.97-14.6), and high risk MIPI score (HR=14, 95% CI 3.38-57.6) were predictive of OS as well as of RFS (HR = 2.76, 95% 1.14-6.69 and HR 6.45, 95% CI 2.41-17.2). Post-ASCT treatment was required for 41% of pts, 8 pts (42.1%) in group A, 38 pts (58.3%) in group B and 5 pts (17.9%) in group C, although pts in group C had shortest follow up to date. In conclusion, our outcomes for pts with newly diagnosed MCL demonstrated no statistically significant difference in OS and RFS among the 3 treatment groups. While longer followup is needed, these data suggest that our less toxic approach of using standard dose and schedule R-CHOP alternating with R-HiDAC, without dose-intense R-CHOP or addition of methotrexate or cisplatin, is highly effective pre-ASCT first line therapy for MCL. Fig 1. Fig 1. Fig. 2 Fig. 2. Disclosures No relevant conflicts of interest to declare.

Patterns of Disease Relapse and Progression in Patients with Multiple Myeloma After First Line Therapy with Autologous Stem Cell Transplantation: Implications for Patient Monitoring After Transplantation

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 825-825
Author(s):  
Dmitriy Zamarin ◽  
Manisha Bhutani ◽  
Danielle Chimento ◽  
Sergio Giralt ◽  
Nikoletta Lendvai ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Soft Tissue ◽  
First Line ◽  
Post Transplant ◽  
First Line Therapy ◽  
Line Therapy ◽  
Group A ◽  
One Year ◽  
Group B

Abstract Abstract 825 BACKGROUND: Autologous stem cell transplantation (ASCT) is a widely used therapeutic option in first line treatment of multiple myeloma (MM). However, many patients eventually relapse. While precise knowledge of relapse and progression (R/PD) patterns would be important to generate evidence based surveillance recommendations after ASCT, such data is limited in the literature, especially in the era following the introduction of the free light chain assay. The purpose of this study is to examine the patterns of post-ASCT relapse and to derive evidence based recommendations for optimal surveillance of patients. METHODS: We performed a retrospective analysis on 258 patients with MM who underwent ASCT within one year of diagnosis at MSKCC between 2000 and 2010, as part of first line therapy. We used the IMWG standard criteria for serologic and clinical R/PD. We first determined for all patients the date of serologic R/PD. Patients identified as having serologic R/PD were further examined to determine whether clinical (anemia, renal failure, hypercalcemia, development of soft tissue lesions), radiologic (skeletal survey) or urinary R/PD had anteceded serologic R/PD. Several groups of patients were derived and further analyzed in terms of relapse patterns and adequacy of follow up. RESULTS: Among 258 patients, 173 were determined to have serologic R/PD at a median of 19.2 months post-transplant. Among these patients, on the dates of their serologic R/PD, 17 (9.8%) had concurrent overt symptomatic evidence of clinical/radiologic R/PD (Group A symptomatic R/PD), while 156 (90.2%) were found to have isolated asymptomatic serologic R/PD without apparent evidence of concomitant clinical/radiologic R/PD (Group B asymptomatic R/PD). Group A included patients with distinct and sometimes coinciding clinical characteristics (poor risk cytogenetics with aggressive disease (n=3), leptomeningeal relapse (n=1), soft tissue relapse (n=4) and acute severe anemia at relapse (n=3)); patients with IgA gammopathy (n=5); and patients considered to have inadequate serologic follow up intervals (range of follow up interval between date of serologic R/PD and prior serologic testing 149 to 245 days) (n=6). Upon further examination of group B, 44 patients had radiologic imaging at the time of serologic R/PD (within 4 weeks following the date of serologic R/PD). Fourteen among them (32%) had evidence of new bone lesions. Among all 173 patients with serologic R/PD, 83 patients had a skeletal survey within one year prior to the date of serologic R/PD. Only 3 (3.6%) had evidence of radiologic R/PD anteceding serologic R/PD. All 3 patients were considered to have had inadequate serologic follow up interval (Range 208 to 252 days). Abnormal urine immunofixation (UIF) anteceded serologic R/PD in 5 out of 41 (12%) patients tested who had achieved CR post transplant. In these patients the abnormal UIF anteceded the serologic R/PD by a mean of 2.4 months. Abnormal UPEP anteceded serologic R/PD by 1.9 months in only 1 out of 40 (2.5%) patients tested who had achieved less than CR post transplant. CONCLUSIONS: Based on the results of this analysis, several conclusions can be drawn: 1) The vast majority of R/PD in patients with MM are asymptomatic R/PD detected first by serologic studies. A small percentage of patients (those with aggressive cytogenetics, specific relapse types including soft tissue, severe cytopenia, and IgA gammopathy) will have symptomatic R/PD with overt concomitant evidence of clinical and/or radiologic R/PD at the time of serologic R/PD; 2) Among patients who have apparent asymptomatic R/PD, a significant percentage will have evidence of skeletal lesions and therefore imaging should be recommended in these patients; 3) In the absence of serological R/PD, routine surveillance screening with yearly skeletal surveys cannot be recommended based on this analysis since this test was not useful in any of the analyzable patients in whom it was obtained; 4) Aside from few patients in CR whose relapse may be detected earlier by UIF (with probably no clinical benefit), all patients with multiple myeloma whose disease progresses will have serologic R/PD at the time of progression and follow up limited to serologic testing may well be sufficient for monitoring patients with MM post transplant. Disclosures: No relevant conflicts of interest to declare.

Lenalidomide, Bendamustine, and Rituximab As First-Line Therapy For Patients >65 Years With Mantle Cell Lymphoma: Preliminary Results From The Nordic Lymphoma Group MCL4 (LENA-BERIT) Phase I-II Trial

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4377-4377 ◽  
Author(s):  
Mats Jerkeman ◽  
Alexandra Albertsson-Lindblad ◽  
Arne Kolstad ◽  
Anna Laurell ◽  
Riikka Räty ◽  
...  
Keyword(s):  
Phase I ◽  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Mantle Cell

Abstract Background Mantle cell lymphoma is a disease of the elderly, with a median age of 70 years. Younger patients may be treated with potentially curative treatment including high dose chemotherapy. For elderly patients, however, no standard therapy has been defined. In the current trial, we investigate if the addition of lenalidomide (LEN) to rituximab (R)+bendamustine (B) (B 90 mg/m2 D1-2 and R 375 mg/m2 D1) followed by maintenance with LEN for 7 months may enhance efficacy, with manageable toxicity, for the older population of MCL patients. Methods Eligibility criteria were age > 65 years, or ≤ 65 years, unable to tolerate high dose chemotherapy, with untreated mantle cell lymphoma, stage II-IV. BR was given for 6 cycles q4w. In the phase I part, the MTD of LEN was established as 10 mg days 1-14 during the induction phase, cycles 2-6. Prednisolone 20 mg days 1-14 was given during cycle 2. When LEN was initially given from cycle 1, we encountered unexpected grade III-IV toxicity in the form of cutaneous and allergic reactions. In the maintenance phase, LEN single therapy was given as follows: cycles 7-8 - 10 mg days 1-21, cycles 9-13 - 15 mg days 1-21. Results The trial was concluded June 1, 2013, after inclusion of 51 patients, of whom 24 were in the phase I part. The median age is 72 years. According to MIPI, 55% were high risk. Presently, 29 patients are evaluable for response after 6 cycles LBR. ORR is 28/29 (97%), CR+CRu 23 (79%). 17 out of 28 evaluable patients (61%) were MRD-negative after 6 cycles. After a median follow-up of 18 months, the median PFS has not been reached, and the estimated PFS at 2 years is 74%. Eight patients have died, 3 due disease progression, 3 due to treatment related toxicity, 1 of lung cancer in a heavy smoker, 1 of CMML. Overall survival at 2 years is 87%. Conclusions When omitted in cycle 1, lenalidomide in combination with R-bendamustine is feasible as first-line therapy in older patients with MCL, and is associated with a high response rate, also as assessed by MRD. The long term efficacy of this regimen remains to be established by longer follow-up. Disclosures: No relevant conflicts of interest to declare.

Gallium scans in the evaluation of residual masses after chemotherapy for seminoma.

1995 ◽  
Vol 13 (11) ◽  
pp. 2784-2788 ◽  
Author(s):  
G P Warren ◽  
L H Einhorn
Keyword(s):  
False Negative ◽  
Fibrous Tissue ◽  
Salvage Chemotherapy ◽  
First Line ◽  
Chemotherapy Group ◽  
Computed Tomographic ◽  
Group A ◽  
Residual Masses ◽  
Group B

PURPOSE To assess the ability of gallium scans to determine whether residual masses consist of viable tumor or necrotic fibrous tissue after chemotherapy for seminoma. PATIENTS AND METHODS Thirty-two patients were enrolled and 27 were assessable. Patients receiving first-line or salvage chemotherapy had gallium scans performed during their first and last scheduled course of chemotherapy and results were compared with restaging computed tomographic (CT) scans and subsequent clinical outcome. RESULTS Of 27 assessable patients, 22 received first-line chemotherapy (group A) and five salvage chemotherapy (group B). Eight patients were not gallium-avid before chemotherapy despite obvious clinical and radiographic evidence of metastatic seminoma. Eighteen of 19 gallium-positive patients had a persistent mass postchemotherapy on abdominal CT. Of 16 patients in group A whose tumors were gallium-avid, all 16 had normalized gallium scans after chemotherapy. However, two of these 16 patients recurred in their original disease site. In group B, there were three patients with gallium-avid tumors and all three had normalized scans postchemotherapy. Two patients who were not gallium-avid (one each in group A and B) also developed recurrent disease. Twenty-four of 27 patients are alive with no evidence of active disease at a median follow-up time of 18 months, including 20 with more than 1 year of follow-up data. CONCLUSION Eight of 27 patients had false-negative gallium scans at the time of diagnosis. All nineteen gallium scans that were initially positive reverted to normal after chemotherapy. Two of 19 patients' follow-up gallium scans were false-negative. We therefore feel that gallium scans have minimal value in the prechemotherapy or postchemotherapy evaluation of metastatic seminoma.

High-Dose Bi-Weekly THP-COP Induction Treatment Followed by High-Dose Therapy with Autologous Peripheral Blood Stem Cell Transplantation for Advanced-Stage Follicular Lymphoma as First-Line Therapy.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5207-5207
Author(s):  
Sadao Aoki ◽  
Jun Takizawa ◽  
Masutaka Higashimura ◽  
Akihito Momoi ◽  
Nobuhiro Tsukada ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Follicular Lymphoma ◽  
Cell Transplantation ◽  
High Dose ◽  
Advanced Stage ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy

Abstract Introduction: Most patients with advanced-stage follicular lymphoma(FL) cannot be cured by conventional chemotherapy and have median survival of 7 to 10 years. High-dose chemotherapy (HDT) supported by autologous stem cell transplantation(ASCT) gives a survival benefit for patients with aggressive lymphoma. Recent several multicenter studies have shown that clinical and molecular remissions can be attained in patients with FL receiving intensified high-dose sequential chemotherapy and autografting. We have reported the efficacy and safety of high-dose bi-weekly THP-COP with G-CSF support (HDBW-TCOPG) for non-Hodgkin’s lymphoma. Therefore, we performed a pilot clinical trial to evaluate the efficacy and toxicity of HDBW-TCOPG followed by HDT with ASCT as first-line therapy in patients with advanced-stage FL. Patients and methods: Between August 1998 and December 2003, 10 Japanese patients with previously untreated FL from whom informed consent was obtained were included in this single-center pilot study. Median age was 48 years. All patients had stage 3 or 4 disease, aaIPI LI 8 and HI 2. Histological subtypes of FL included grade 1 4; grade 2 4; grade 3a 2. HDBW-TCOPG consisted of pirarubicin 70 mg/m2 on day 1; cyclophosphamide 1000 mg/m2 on day 1; vincristine 1.4 mg/m2 on day 1; predonisolone 50 mg/m2 from day 1 to 5; lenograstim 2.0 mg/kg/day from day 3. Five patients who enrolled after rituximab was approved for indolent B-cell lymphoma in Japan received induction therapy combined HDBW-TCOPG with rituximab 375mg/m2 on day -2 (R-HDBW-TCOPG). Six cycles were administered at intervals of two weeks. PBSC were collected during the later cycles of HDBW-TCOPG or on the recovery of high-dose etoposide regimen (500mg/m2 for 3 days) administered after the completion of HDBW-TCOPG. Leukaphereses were performed until a minimum of 2.0x106/kg CD34+ cells had been collected. The conditioning regimen consisted of ranimustine 200mg/m2 on day-7 and -2; paraplatin 300mg/m2 on day -6, -5, -4, -3; etoposide 500mg/m2 on day −5, −4, −3; cytarabine 2.5 g/m2 every 12 hours on day −2, −1 (MCE-CA regimen) in 2 patients or cyclophosphamide 50mg/kg on day −2, −1 (MCEC regimen) in 8 patients. Results: Sufficient numbers of PBSC were collected in 5 of 7 patients mobilized with HDBW-TCOPG and in all 5 patients with high-dose etoposide. The median time to reach total number of leukocytes of 1.0 x109/l was nine days (range 8–11). All 10 patients who were in PR at the end of HDBW-TCOP(G) achieved CR post APBSCT. After a median follow up of 36.6 months (range 7–66 months) PFS and OS are 90% and 90%, respectively, for all patients. One patient developed secondary myeloid leukemia with t(3;21) and died at 35 months after APBSCT without signs of recurrence of lymphoma. Another patient who relapsed at 35 months after transplantation. IgH or BCL2 rearrangement was detected by PCR analysis prior to therapy in three patients and one of them still showed detectable disease after HDBW-TCOPG induction. However, all three patients demonstrated MRD negativity after HDT with ASCT. Conclusion: HDBW-TCOPG as induction therapy followed by HDT with ASCT is feasible for advanced-stage FL with acceptable toxicity, and this short term highly intensified therapy may induce cure of the disease by minimizing MRD, but longer follow up is needed to evaluate the impact on survival.

Nilotinib Versus High-Dose Imatinib in Early Chronic Phase CML Patients Who Have Suboptimal Molecular Responses to Standard-Dose Imatinib: Updated Data From RE-Nice Study

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3775-3775 ◽  
Author(s):  
Soo-Young Choi ◽  
Sung-Eun Lee ◽  
Soo-Hyun Kim ◽  
Eun-Jung Jang ◽  
Jin-hwa Lee ◽  
...  
Keyword(s):  
Dose Escalation ◽  
Standard Dose ◽  
Chronic Phase ◽  
Cytogenetic Response ◽  
High Dose ◽  
Molecular Response ◽  
Long Term Outcomes ◽  
First Line

Abstract Abstract 3775 Background. In chronic myeloid leukemia (CML), achievement of optimal responses by time point has improved long-term outcomes. In contrast, several clinical studies investigating the clinical implications of suboptimal response showed that patients with suboptimal responses tend to have poor long-term outcomes. In IRIS study, patients who achieved major molecular response (MMR) at 18 months had event-free survival (EFS) benefit, compared to those who achieved complete cytogenetic response (CCyR) without MMR. However, the best treatment for these patients is still not confirmed. By the previous studies, sustaining standard-dose of imatinib (IM) is expected to yield less than 20 percent of additive MMR. In this prospective study, we investigated whether switching to nilotinib (NIL) or high-dose IM may be more effective for patients with suboptimal molecular response to IM as first-line therapy. Methods. Early chronic phase (CP) CML patients who have achieved CCyR but no MMR after at least 18 months and up to 24 months (≤ 18 to ≥24 months) on first-line IM therapy at a daily dose of 400 mg were enrolled in this clinical trial, and informed consents were obtained from all patients. In NIL arm, patients received oral dose of 400 mg BID (800 mg/day) and in high-dose IM arm, patients received 800 mg/day administrated as 400 mg BID. Primary endpoint is to evaluate the cumulative MMR rates by 12 months, and secondary endpoints are to evaluate the cumulative MMR, MR4.0 and undetectable molecular residual disease (UMRD) rates during further 24 month follow-up. Safety profiles will also be assessed. Patients showing lack of response (lack of complete hematologic response (CHR) at 6 months, increasing WBC, no major cytogenetic response (MCyR) at 24 months), loss of response (loss of CHR or MCyR) or severe intolerance to treatment were allowed to crossover to the alternative treatment. Results. With a data cut-off date of 10 Jul 2012, a total of 43 patients were randomized into NIL arm (n = 22) or high-dose IM arm (n = 21). With a median follow-up of 15 months (range, 1–36), all patients have maintained CCyR without progression to advanced disease, and progressive decrease in BCR-ABL1 transcript levels was observed in all patients. Cumulative incidence (CI) of MMR by 12 months showed no significant difference between NIL arm and high-dose IM arm (37.8 ± 11.9% vs 34.8 ± 10.6%, P = 0.789). In NIL arm, 3 in 22 (14%) and 2 in 22 (9%) patients achieved MR4.0 and UMRD, respectively, and in high-dose IM arm, 1 in 21 (5%) patients achieved MR4.0. Overall, the patients treated with high-dose IM showed toxicities more frequently, such as fatigue, dyspnea and decreased phosphate. In addition, 10 patients in high-dose IM arm have cross-over to NIL treatment due to lack of response (n=9) and intolerance (n=1), and the median duration of NIL treatment was 14 months (range, 7–26 months). Among them, 5 (50%) patients have achieved MMR with a median NIL treatment duration of 12 months (range, 3–18). Conclusions. These results demonstrate that early switching to NIL or dose escalation of IM could be recommended, considering the results of standard dose of IM in suboptimal molecular responders. When the tolerability of treatment was considered for switching to NIL or high-dose IM, NIL may be preferred. Through further clinical investigation on a large patient population and longer period observation, the efficacy and safety of early intervention of suboptimal molecular response using NIL or dose escalation of IM will be needed. Updated data with longer follow-up duration will be presented in the meeting. Disclosures: No relevant conflicts of interest to declare.

scholarly journals The Outcome of Mantle Cell Lymphoma patients after Treatment Failure and Prognostic value of Secondary Mantle Cell International Prognostic Index (sec MIPI)

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4425-4425 ◽  
Author(s):  
Marek Trneny ◽  
Pavel Klener ◽  
David Belada ◽  
Heidi Mocikova ◽  
Vit Prochazka ◽  
...  
Keyword(s):  
High Risk ◽  
Treatment Failure ◽  
Prognostic Value ◽  
High Dose ◽  
Line Treatment ◽  
First Line ◽  
Single Drug ◽  
Mantle Cell ◽  
First Line Treatment

Abstract Background: MCL is a distinct lymphoma entity with improved outcome achieved by the introduction of rituximab, high dose Ara-C and autologous stem cell transplantation (ASCT) into the first line therapy. The outcome of the relapsed patients (pts) remain however poor and there is little data on the outcome after subsequent relapses and there is no information on secondary MIPI prognostic value. Aim: To analyze the outcome of the MCL patients after first line treatment failure and to evaluate the prognostic role of the sec MIPI which is MIPI calculated at the time of relapse/progression. Methods: This analysis is a part of the Lymphoma project in which consecutive lymphoma patients are registered since the year 1999. Altogether 519 newly diagnosed MCL patients were registered in 5 university centers and 9 regional departments between 1999 and 2011. Patients who were treated with rituximab as part of the first line treatment (n=388) were included into the analysis. The diagnoses were confirmed according to WHO classification in the reference pathology centers. The median follow up is 4.5 years. Results: The whole cohort consists of 261 males and 127 females (2.1:1) with median age 65 y (28-87), the majority of pts had advanced disease (CS IV in 81.6% pts), PS ECOG ≥ 2 in 23.6% pts, elevated LDH in 52.5% of pts. The MIPI risk profile was as follows: low risk 21.7%, intermediate risk 27.2% and high risk in 51.1%. All pts received rituximab as part of the induction, 48.7% pts received CHOP, 5.7% alternation of CHOP and HD Ara-C, 26.2% intensive induction with HD Ara-C, 10.3% CVP, 6.4% FC. High dose therapy with ASCT was performed in 23.9% of pts. The ORR was 89.0% with 63.8 CR/CRu, 6.3% had stable disease and 4.9% were primary progressive. The PFS and OS were 2.9 y and 5.5 y with significant impact of MIPI risk (p<0.0001) for both PFS and OS. There were observed 179 relapses/progressions (R/P) and 70 deaths not related to subsequent progression. The cohort of patients with 1st R/P consisted out of 125 males and 54 females (2.3:1) with median age 68 years (38-89). The sed MIPI at the time of 1st R/P was low in 12.7% pts, intermediate in 32.1% and high 59.8% pts. Rituximab was used in 69.5% of patients, DHAP or ESHAP was used in 25.1% cases, FC in 22.8% of cases, CHOP like regimen in 9.4%, HD Ara-C in 11.8%, only 4.7% were treated with targeted therapy temsirolimus or lenalidomide. Altogether 77.2% pts were treated with the polychemotherapy and 22.8 with monotherapy. ASCT and AlloSCT were performed in 5.5% and 8.7% pts resp. During follow up there were observed 74 deaths not related to subsequent progression and 53 2nd R/Ps. The median of 2nd PFS and 2nd OS from the date of 1st R/P was 1.0 and 1.3 years resp. The sec MIPI low vs. intermediate vs. high risk had significant prognostic impact on 2nd PFS: 5.8 vs 1.7 vs 0.9 years (p<0.0001) (fig 1) as well as on OS : 5.8 vs 3.4 vs 1.1 years (p<0.0001) (fig 2). The cohort of 53 pts with 2nd R/P had median age 68 (38-85) yers, male/female ratio was 1.4. Rituximab was used in 45.9% of treated patients and 48.3% of pts were treated with single drug. During follow up 11 pts developed 3rd R/P and other 30 pts died due to current progression, toxicity or in remission. The median of 3rd PFS from the time of 2nd R/P was 6.8 m and OS 7.4 months. Pts who were treated for 3rd R/P recieved rituximab in 50% of cases and the majority (81.2%) were treated with other single drug. The median of 4th PFS from 3rdR/P was 4.9 m and OS 5.5 months . Conclusions: Our analysis of relapsed MCL patients shows that 1: Median PFS from the Dg was 2.9 y but each subsequent relapse resulted in significantly shorter PFS median 12.1, 6.8 and 4.9 months resp. 2: The median OS from Dg was 5.5y but after each relapse it became shorter - 15.7 m, 7.4 m and 5.5 months resp. 3: The sec MIPI at the time of relapse discriminates the groups with significantly different prognosis. Disclosures No relevant conflicts of interest to declare.

scholarly journals A comparative study for the effectiveness of Tamsulosin alone versus Tamsulosin plus Tadalafil combination as an expulsive medical treatment in the management of lower ureteric calculous in Al-Diwaniyah teaching hospital

2019 ◽  
Vol 10 (2) ◽  
pp. 1551-1555
Author(s):  
Ahmed Abdulameer Alwan ◽  
Hussain T. Ajeel ◽  
Ahmed Hamza Abd
Keyword(s):  
Medical Treatment ◽  
Equal Treatment ◽  
Expulsion Rate ◽  
Treatment Groups ◽  
Ureteric Calculi ◽  
Group A ◽  
Male Patients ◽  
Group B ◽  
Urology Clinic

To evaluate the efficacy & safety of tamsulosin alone versus tamsulosin plus tadalafil combination as expulsive medical treatment of distal ureteric calculus. From March 2015 utile March 2017, two hundred patients (one hundred thirty males and seventy females), who attended the outpatient urology clinic and presented with stones size 5 to 10 mm in distal ureteric part, have been randomly allocated into two equal treatment groups. Group A treated with tamsulosin alone, and group B treated with tamsulosin plus tadalafil. Both treatments were given for a maximum of six weeks’ duration. The rate and time to the calculous passage, type of analgesic use, adverse effects of the drugs, number of outpatient urology clinic visits for pain, and follow-up were noted. Both treatment groups have higher expulsion rate with a lower time to expulsion with no statistically significant differences between them (p=0.350, p=0.074, respectively). Group B showed a significantly lower rate in admission to the hospital for pain and need for analgesia than in group A. no dangerous adverse events had been observing in both groups. Additional benefit seen in group B was the improvement in erectile function regarding male patients. Using tamsulosin and tadalafil as an expulsive medical treatment for distal ureteric calculous is safe and efficacious. Such combination therapy may provide additional advantages in cases of erectile dysfunction co-exist with distal ureteric calculi.

A population-based study evaluating metastatic renal cell cancer (mRCC) patients treated with interferon (IFN) alone, first-line IFN then second-line sunitinib, or sunitinib alone

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 15572-15572 ◽  
Author(s):  
C. K. Kollmannsberger ◽  
D. Y. Heng ◽  
N. Murray ◽  
K. N. Chi
Keyword(s):  
Overall Survival ◽  
Standard Treatment ◽  
Population Based ◽  
Phase Iii ◽  
Second Line ◽  
First Line ◽  
Group A ◽  
Group B ◽  
The Impact

15572 Background: Previously, immunotherapy agents such as IFN were the only treatments available for mRCC. Sunitinib has demonstrated prolonged progression free survival in a phase III trial but overall survival benefit has yet to be determined and few patients (pts) with poor MSKCC prognostic profiles were included. Methods: The province-wide BC Cancer Agency Registry was cross-referenced to the central pharmacy database to identify all pts with the diagnosis of mRCC who were treated with IFN and/or sunitinib. Sunitinib became available after October 2005 under an expanded access program or as standard treatment. Three groups of pts were identified: Group A consisted of pts who received IFN alone between January 2003 to October 2005, Group B was all pts who progressed on first-line IFN after October 2005 and subsequently were treated with second-line sunitinib and Group C was all pts treated with first-line sunitinib. Baseline characteristics and overall survival were collected on all patients. Results: A total of 75 patients were identified with 36 patients in Group A, 23 patients in Group B, and 16 patients in Group C. Data are reported from the initiation of IFN in Group A and the initiation of sunitinib in Groups B and C. Median follow-up was 6.0 months in group A, 7.6 months in group B, and 6.2 months in group C. Median age of treatment initiation (62y vs. 60y vs. 62y), number of metastatic sites (>1 site in 63% vs. 61% vs. 56%), and Karnofsky performance status (79 vs. 86 vs. 81) were similar between groups A, B and C, respectively. The MSKCC prognostic profiles were favorable, intermediate and poor in 26%, 51% and 23% in group A, 17%, 65% and 17% in group B and 31%, 38% and 31% in group C, respectively. The estimated 6-month overall survival in groups A, B and C was 56%, 72% and 100%, respectively (log rank A vs C p=0.009; log rank B vs C p=0.042). Conclusion: With the limitations of retrospective analysis and preliminary follow-up, the introduction of sunitinib as standard treatment into the general population of patients with mRCC appears to be associated with a longer overall survival compared to patients treated with IFN alone. Population-based analysis on the impact of the introduction of sunitinib therapy is ongoing. No significant financial relationships to disclose.

KEYNOTE-604: Pembrolizumab (pembro) or placebo plus etoposide and platinum (EP) as first-line therapy for extensive-stage (ES) small-cell lung cancer (SCLC).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 9001-9001 ◽  
Author(s):  
Charles M. Rudin ◽  
Mark M. Awad ◽  
Alejandro Navarro ◽  
Maya Gottfried ◽  
Solange Peters ◽  
...  
Keyword(s):  
Standard Dose ◽  
Rank Test ◽  
P Value ◽  
First Line ◽  
Double Blind ◽  
First Line Therapy ◽  
Significance Threshold ◽  
Line Therapy ◽  
Ecog Ps

9001 Background: Pembro monotherapy showed durable antitumor activity as third-line or later therapy for metastatic SCLC, leading to FDA approval in that setting. KEYNOTE-604 was a double-blind, phase 3 study of pembro + EP vs placebo + EP as first-line therapy for ES-SCLC (NCT03066778). Methods: Eligible patients (pts) with previously untreated ES-SCLC and no untreated CNS metastases were randomized 1:1 to pembro 200 mg Q3W or saline placebo for up to 35 cycles plus 4 cycles of standard-dose EP. Pts with CR or PR after cycle 4 could receive PCI at investigator discretion. Randomization was stratified by platinum choice (carboplatin vs cisplatin), ECOG PS (0 vs 1), and LDH (≤ULN vs > ULN). Primary endpoints were OS and PFS (RECIST v1.1, blinded central review) in the ITT population. ORR, DOR, and safety were secondary endpoints. OS and PFS treatment differences were assessed by the stratified log-rank test. The protocol specified 2 interim analyses (IAs) and a final analysis (FA). Prespecified efficacy boundaries were one-sided P = 0.0048 for PFS at IA2 (prespecified final PFS analysis) and 0.0128 for OS at FA. Results: 453 pts were randomized. 223/228 pts assigned to pembro + EP and 222/225 assigned to placebo + EP received ≥1 dose of assigned treatment; 1 pt assigned to pembro + EP received placebo + EP in error. Median age was 65 y, 74% had ECOG PS 1, and 57% had LDH > ULN; more pts in the pembro + EP arm had baseline brain metastases (14% vs 10%). At FA (median follow-up, 21.6 mo), 9% of pts in the pembro + EP arm and 1% in the placebo + EP arm remained on study treatment; 12% and 14% received PCI. At IA2 (median follow-up, 13.5 mo), pembro + EP significantly improved PFS in the ITT population (HR 0.75 [95% CI 0.61-0.91], P = 0.0023; median 4.5 vs 4.3 mo). At FA, pembro + EP prolonged OS in the ITT population, but the significance threshold was not met (HR 0.80 [95% CI 0.64-0.98], P = 0.0164; median 10.8 vs 9.7 mo). In a post hoc analysis of OS in the as-treated population, the nominal P value was smaller than the significance threshold (HR 0.78 [95% CI 0.63-0.97], P = 0.0124). ORR at FA was 71% for pembro + EP vs 62% for placebo + EP; median DOR was 4.2 vs 3.7 mo. Observed AEs were as expected; any-cause AEs were grade 3-4 in 77% vs 75%, grade 5 in 6% vs 5%, and led to discontinuation in 15% vs 6%. Conclusions: Pembro + EP significantly improved PFS and prolonged OS compared with placebo + EP as first-line therapy for pts with ES-SCLC. No unexpected toxicities were seen with pembro + EP. These data support the benefit of pembro-containing regimens for ES-SCLC. Clinical trial information: NCT03066778.

Autologous Stem Cell Transplantation as First Line Therapy in Peripheral T Cell Lymphomas. Update of a Prospective Multicenter Study.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 904-904 ◽  
Author(s):  
Peter Reimer ◽  
Thomas Ruediger ◽  
Tobias Schertlin ◽  
Eva Geissinger ◽  
Florian Weissinger ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Lymphoma ◽  
High Dose ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
T Cell Lymphomas ◽  
Peripheral T Cell Lymphomas

Abstract Peripheral T-cell lymphomas (PTCL) represent a heterogeneous group of non-Hodgkin’s lymphomas, which in general show a poor outcome following conventional chemotherapy. Long-term remissions are achieved in only 15 to 35 %. However, the impact of more aggressive therapeutic approaches such as myeloablative therapy with autologous stem cell transplantation (ASCT) as first line therapy is poorly defined mainly due to the lack of prospective PTCL-restricted studies. In 6/00 we initiated the first prospective PTCL-restricted multicenter study of myeloablative radiochemotherapy in primary diagnosed PTCL. The results of the first 30 patients (pts) are in press. We update our data on all pts entering the study. Study design: Pts < 65 years with PTCL of all subtypes without primary cutaneous lymphoma and ALK1 expressing anaplastic large cell lymphoma were included. Treatment consisted of 4–6 courses of CHOP protocol followed by DexaBEAM or ESHAP regimen and collection of stem cells. Subsequently pts underwent total body irradiation (TBI) and high dose cyclophosphamide chemotherapy (60 mg/kg body weight) with ASCT. Patient characteristics: From 6/00 to 8/04 65 pts (42 male) with a median age of 50 years were enrolled. Main subtypes were Peripheral T-cell lymphoma not otherwise specified (NOS, n= 26) and Angioimmunioblastic T-cell lymphoma (AILT, n= 19). According to the Ann Arbor classification, 81% of the pts had stage III/IV disease. The International Prognostic Index (IPI) was low/low intermediate in 54% and intermediate high/high in 46% of the pts, respectively. Results: So far 54 of 65 pts are eligible for evaluation, while the remaining 11 pts are still under therapy. Thirty-three pts could be transplanted (61%). After a median follow up of 10 months after transplantation 22 pts (67%) are in sustained remission and 8 pts (27%) had relapsed. Post transplantation two pts died treatment-related (one secondary AML, one multiorgan failure). Twenty-one pts (39%) did not proceed to ASCT mainly due to progressive disease (n= 16). Treatment-related toxicity was comparable to other high-dose studies in malignant lymphomas. Conclusion: Our data show feasibility and efficacy of first-line ASCT following myeloablative radiochemotherapy in PTCL. Sustaining remission seems achievable for a majority of pts. However, additional treatment strategies are required to prevent early progression prior myeloablative therapy. Longer follow-up is necessary to confirm long-term remission rate.

Sign in / Sign up

Export Citation Format

Share Document