Primary Treatment of Waldenstrom's Macroglobulinemia with Dexamethasone, Rituximab and Cyclophosphamide (DRC): Final Analysis of a Phase II Study

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 438-438 ◽  
Author(s):  
Meletios A. Dimopoulos ◽  
Maria Roussou ◽  
Efstathios Kastritis ◽  
Evdoxia Hadjiharissi ◽  
Marie-Christine Kyrtsonis ◽  
...  
Keyword(s):  
Median Time ◽  
Progressive Disease ◽  
Alkylating Agents ◽  
Primary Treatment ◽  
Line Treatment ◽  
Second Line ◽  
Time To Progression ◽  
Minor Response ◽  
A Minor

Abstract Abstract 438 Between November 2002 and April 2006, 72 patients with Waldenstrom's Macroglobulinemia (WM) were enrolled in this multicenter trial of primary treatment with DRC which consisted of dexamethasone 20mg IV followed by rituximab 375 mg/m2 IV on day 1 and oral cyclophosphamide 100 mg/m2 bid on days 1 to 5 (total dose 1000 mg/m2). DRC courses were repeated every 21 days for six courses and then patients without progressive disease were observed without treatment. Patient characteristics, toxicity and response data have been reported previously (Dimopoulos et al, J Clin Oncol 2007;25:3344): 83% of patients achieved a response including 7% complete, 67% partial and 9% minor responses. In June 2012 we updated this study (minimum follow-up >6 years) in order to assess time to progression, time to next treatment, type and response of second-line treatment, overall survival (OS) and cause-specific survival (CSS) in which deaths unrelated to WM or complications of treatment were censored. Second line treatment was administered to patients who experienced progressive disease and also met criteria for treatment requirement based on consensus recommendations (Kyle et al, Sem Oncol 2003;30:116). The median time to progression was 35 months (95% Confidence Interval: 22–48 months) and the median time to next treatment requirement was 51 months. Among several factors who were analyzed for their possible correlation with shorter time to progression, only lymphadenopathy was significant (p=0.028). Among 40 patients who received second line treatment, 28 patients were retreated with either rituximab alone (n=7) with DRC (n=11) or with rituximab combined with other agents (n=10) and 23 patients (82%) achieved a minor response or better. The remaining 12 patients were treated with alkylating agents (n=5), with nucleoside analogues (n=4) with bortezomib (n=2) or with high dose therapy (n=1) and 8 patients achieved a minor response or better. So far 35 (49%) patients have died including 15 patients from unrelated causes (4 lung cancer, 1 bladder cancer, 1 melanoma, 1 gastric cancer, 1 pancreatic cancer, 4 complicated of heart diseases, 2 stroke and 1 pancreatitis). One patient, who received further therapy with fludarabine, developed myelodysplastic syndrome and 2 patients developed diffuse large-B cell lymphoma (one after DRC and one after multiple treatments which included alkylating agents and fludarabine). The probability for 5-year OS and CSS is 62% and 78%, respectively while median OS and CSS is 95 and 104 months respectively (figure). Post progression survival was 82 months and median survival after second line therapy was 82 months. The International Prognostic Staging System (IPSS) is predictive for OS. The probability for 5-year OS is 100%, 67% and 48% for patients with low-, intermediate- and high- risk WM (p=0.005). We conclude that this long-term follow-up analysis of the original phase II study showed that the DRC regimen is associated with a significant median time to progression of about 3 years and that most patients who develop disease progression respond again to rituximab-based regimens. So far, this regimen has not been associated with development of secondary myelodysplasia. The DRC regimen represents an active and safe treatment choice for patient with symptomatic WM. Disclosures: No relevant conflicts of interest to declare.

Primary Treatment of Waldenstrom's Macroglobulinemia with Dexamethasone, Rituximab and Cyclophosphamide (DRC): Long Term Follow-up Analysis of a Phase II Study.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2887-2887
Author(s):  
Meletios A. Dimopoulos ◽  
Evdoxia Hadjiharissi ◽  
Marie-Christine Kyrtsonis ◽  
Argiris Symeonidis ◽  
Panayiotis Repoussis ◽  
...  
Keyword(s):  
Median Time ◽  
Progressive Disease ◽  
Primary Treatment ◽  
Line Treatment ◽  
Second Line ◽  
Time To Progression ◽  
Minor Response ◽  
Long Term Follow Up ◽  
A Minor

Abstract Abstract 2887 Poster Board II-863 Between November 2002 and April 2006, 72 patients with Waldenstrom's Macroglobulinemia (WM) were enrolled into this multicenter trial of primary treatment with DRC which consisted of dexamethasone 20 mg IV followed by rituximab 375mg/m2 IV on day 1 and oral cyclophosphamide 100 mg/m2 bid on days 1 to 5 (total dose 1000 mg/m2). DRC courses were repeated every 21 days for six courses and then patients without progressive disease were observed without treatment. Patient characteristics, toxicity and response data have been reported previously (Dimopoulos et al, J Clin Oncol 2007; 25:3344): 83% of patients achieved a response including 7% complete, 67% partial and 9% minor responses. In June 2009 we updated this study (minimum follow-up >3 years) in order to assess time to progression, time to next treatment, type of second-line treatment and response to this, overall survival (OS) and cause-specific survival (CSS) in which deaths unrelated to WM or complications of treatment were censored. Second line treatment was administered to patients who experienced progressive disease and also met criteria for treatment requirement based on consensus recommendations (Kyle et al, Sem Oncol 2003; 30:116). As of June 2009, 42 patients fulfilled the criteria for progressive disease (Kimby et al, Clin Lymphoma Myeloma 2006; 6:380) but 14 patients have not yet required second line treatment. The median time to progression was 35 months (95% Confidence Interval: 22-48 months) and the median time to next treatment requirement was 51 months. Among several factors who were analyzed for their possible correlation with shorter time to progression, only lymphadenopathy was significant (p<0.01), while splenomegaly was of borderline significance (p=0.06). Among 28 patients who received second line treatment, 19 patients were retreated with either rituximab alone (n=7) with DRC (n=8) or with rituximab combined with other agents (n=4) and 16 patients (84%) achieved a minor response or better. The remaining 9 patients were treated with alkylating agents (n=3), with nucleoside analogues (n=3) with bortezomib (n=2) or with high dose therapy (n=1) and 6 patients achieved a minor response or better. So far 27 patients (38%) have died including 11 patients from unrelated causes (3 lung cancer, 1 bladder cancer, 1 melanoma, 1 gastric cancer, 1 pancreatic cancer, 2 congestive heart failure, 1 cerebral stroke and 1 pancreatitis). No patient developed myelodysplastic syndrome or secondary AML and one patient developed diffuse large B-cell lymphoma. The probability for 5-year OS and CSS is 59% and 74%, respectively. The International Prognostic Staging System (IPSS) is predictive for both OS and CSS. The probability for 5-year OS is 100%, 67% and 43% for patients with low-, intermediate- and high-risk WM according to IPSS (p<0.01). Furthermore, the probability for 5-year CSS is 100%, 81% and 62% for patients with IPSS low-, intermediate- and high-risk WM (p=0.05). We conclude that this long-term follow-up analysis of the original phase II study showed that the DRC regimen is associated with a significant median time to progression and that most patients who develop disease progression respond again to rituximab-based regimens. So far, this regimen has not been associated with development of secondary myelodysplasia. The DRC regimen represents an active and safe treatment choice for patients with symptomatic WM. Disclosures: No relevant conflicts of interest to declare.

Late Relapses Characterize Autologous Transplantation (ASCT) in First Complete Remission (CR) for Peripheral T-Cell Lymphoma (PTCL).

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 5110-5110 ◽  
Author(s):  
Tarun Kewalramani ◽  
Steve Horwitz ◽  
Andrew D. Zelenetz ◽  
Stephen D. Nimer ◽  
Craig H. Moskowitz
Keyword(s):  
T Cell ◽  
Median Time ◽  
Progressive Disease ◽  
Cell Lymphoma ◽  
Autologous Transplantation ◽  
Conditioning Regimen ◽  
Allogeneic Transplantation ◽  
T Cell Lymphoma ◽  
Time To Progression

With the exception of ALK-positive anaplastic large cell lymphoma (ALCL), standard-dose chemotherapy is curative in a minority of patients (pts) with PTCL, and most pts have progressive disease less than 2 years from completing treatment. Several studies suggest that ASCT in 1st CR significantly improves the short-term outcome of pts with PTCL, but its long-term efficacy is not known. To address this, we assessed the outcome of sequential patients who underwent ASCT in 1st CR (n=15). Histologic subtypes were PTCL, unspecified, in 6 pts, angioimmunoblastic T-cell lymphoma in 5 pts, ALK-negative ALCL in 3 pts and hepatosplenic gamma delta T-cell lymphoma in 1 pt. Induction chemotherapy was CHOP (n=2) or CHOP-ICE hybrid (n=12) in 93% of pts. The age-adjusted IPI (AAIPI) was 2–3 in 9 of 14 assessable patients (64%), and 11 pts (73%) had stage III–IV disease. The conditioning regimen consisted of BEAM or CBV in 10 pts and TBI/Cy/VP-16 in 5 pts. All patients received peripheral blood progenitor cells for hematopoietic support. The median follow-up of all patients is 24 months (range 4.5–70). Five pts (33%) have progressed, with a median time to progression of 50 months (range 10–70). Four of the 5 pts who progressed did so more than 2 years from ASCT; they comprise 57% of patients with more than 2-years of follow-up. Four of 5 patients with progressive disease have died, with a median time from progression to death of 1 month (0.6–14.6). In this small series the AAIPI was not predictive of PFS or OS. While our results confirm the that ASCT in 1st CR significantly delays the time to progression, they suggest that it may not be curative in the majority of patients. If confirmed in ongoing larger prospective studies, this observation warrants trials of post-ASCT maintenance treatment and, for younger patients, trials of allogeneic transplantation in 1st CR or sequential ASCT followed by allogeneic transplantation. Figure Figure

Survival After Second, Third, and Fourth Line Therapy Better Than Expected in Patients with Previously Treated AL Amyloidosis Who Were Not Transplant Candidates At Diagnosis.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 946-946 ◽  
Author(s):  
Girindra G Raval ◽  
Morie A Gertz ◽  
Martha Q Lacy ◽  
Suzanne R Hayman ◽  
Shaji K. Kumar ◽  
...  
Keyword(s):  
Overall Survival ◽  
Median Time ◽  
Al Amyloidosis ◽  
Line Treatment ◽  
Second Line ◽  
Treatment Regimens ◽  
Line Therapy ◽  
Previously Treated ◽  
Better Than

Abstract Abstract 946 Background: The emerging therapies directed at the plasma cell clone have dramatically increased overall survival (OS) for both myeloma and amyloidosis patient populations. As more treatment trials are done in patients (pts) with AL, benchmarks for outcomes among previously treated AL pts are required, especially for those pts who are not candidates for high-dose chemotherapy with peripheral blood stem cell transplantation (ASCT). Inadequate information is available about the number of non-transplant pts who go on to receive second line treatment for AL amyloidosis. Methods: To ascertain the outcomes of pts who did not receive ASCT as primary therapy but who required a second line of therapy, we reviewed the experience of pts seen at Mayo Rochester between 1990 and 2010 according to an IRB approved retrospective review protocol. 1828 pts had their first Mayo visit for AL during this time period. Pts were excluded from this study for the following reasons: 571 had upfront transplant; 907 pts had received only one line of treatment for their amyloid; 91 had longstanding other associated malignancy [Waldenstrom's macroglobulinemia (8), lymphoma (15), CLL (6), multiple myeloma (62)]; and 93 had inadequate follow-up information. One-hundred and sixty-six pts received 2 or more lines of therapy for their AL amyloid and are the subject of these analyses. Statistical analyses were done using JMP statistical software (SAS, Carey, NC). Results: Of the 166 pts, the median age was 64 years (range 34, 84). 49% were male. Baseline organ involvement was as follows: cardiac 84/166 (50%); renal 118/166 (71); liver 23/166 (13.8%); peripheral nerves 19/166 (11.4%); and gastrointestinal 14/166(8.4%). Thirty-one percent (52/16) had both cardiac and renal involvement. Only 73 pts had cardiac biomarkers (NT pro BNP and Troponin T) done at baseline. Of these pts, 26% were stage 1, 49.3% were stage 2, and 24.6% were stage 3 according to original Mayo cardiac biomarker staging system. By inclusion criteria definition, all 166 pts received 1st and 2nd line therapies; 53 (32%) pts received 3rd line of treatment; 20 (12%) received 4th line of treatment; and 10 (6%) received 5th line of treatment. For first line therapy, the most common drugs given either singly or in combination were corticosteroid (147/166; 88.5 %), alkylator (99/166; 59.6%), IMID (34/166; 20.4 %), and bortezomib (19/166; 11.4%). The median time from diagnosis to 2nd line therapy was 10.3 months. Second line regimens received included: corticosteroid, 108/166 (65.1%); alkylator, 76/166 (45.8 %); IMID, 46/166 (27.7%); and bortezomib, 46/166 (27.8%). The median time from diagnosis to 3rd line therapy was 19.8 months. For the 53 pts who received 3rd line treatment, regimens included: corticosteroid, 41/53 (77.3%); IMIDs, 17/53 (32.1%); alkylator, 17/53 (32.1%); bortezomib, 12/53 (22.6%). The median time from diagnosis to 4th line therapy was 31.8 months. For the 20 pts receiving 4th line treatment, regimens included: corticosteroids, 15/20(75%); alkylator, 12/20 (60%), bortezomib, 7/20 (35%); and IMIDs, 4/20(20%). Eighty-three pts have died. The 1 year mortality of our study population was only 8%. The median follow-up of surviving pts was 47.6 months. Figure 1 demonstrates Kaplan-Meier estimates of overall survival (OS) from initiation of each successive therapy. The median OS from initiation of 1st, 2nd, and 3rd lines of treatment were 65, 49.5 and 36.7 months respectively. The median OS after the 4th line of treatment was not reached. The 4 year OS rates from initiation of 1st, 2nd, 3rd and 4th lines of therapy were 58%, 50.8 %, 50 % and 53.4% respectively. Conclusion: Outcomes among relapsed or refractory AL pts are better than what one might expect. Multiple publications have demonstrated that the 1 year mortality of newly diagnosed AL is in the vicinity of 40%. Thereafter, the rate at which pts die dramatically decreases. Our study provides explicit data characterizing the fate of pts unfortunate enough to require additional therapy but fortunate enough to survive past the exceedingly high risk period of death that occurs within 6–12 months of diagnosis. These data provide useful information for benchmarking future trials for treatments of AL amyloidosis. Disclosures: No relevant conflicts of interest to declare.

scholarly journals First-Line Treatment with a Cyclin-Dependent Kinase 4/6 Inhibitor Plus an Aromatase Inhibitor for Metastatic Breast Cancer in Alberta

2021 ◽  
Vol 28 (3) ◽  
pp. 2270-2280
Author(s):  
Carla P. Amaro ◽  
Atul Batra ◽  
Sasha Lupichuk
Keyword(s):  
Aromatase Inhibitor ◽  
Median Time ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Line Treatment ◽  
Second Line ◽  
Cyclin Dependent Kinase ◽  
Time To Progression ◽  
First Line ◽  
First Line Treatment

In this analysis, we describe population-based outcomes for first-line treatment with a cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) combined with an aromatase inhibitor (AI). All patients who were prescribed CDK4/6i + AI from January 2016 through June 2019 were included. Patient demographics, tumour and treatment characteristics were collected and described. Survival distributions were estimated using the Kaplan–Meier method. Multivariate analysis (MVA) was constructed to examine associations between potentially prognostic clinical variables and progression-free survival (PFS). In total, 316 patients were included. The median age was 61 years. After a median follow-up of 28.1 months, the median PFS was 37.9 months (95% CI, 26.7–NR). In the MVA, PR-negative tumour (HR, 2.37; 95% CI, 1.45–3.88; p = 0.001) and CDK4/6i dose reduction (HR, 1.51; 95% CI, 1.06–2.16; p = 0.022) predicted worse PFS. Median overall survival (OS) was not reached. The 30-month and 36-month OS rates were 74% and 68%, respectively. Of patients who progressed, 89% received second-line treatment. Median time to progression on second-line chemotherapy was 9.0 (5.8–17.6) months, and median time to progression on second-line hormonal therapy +/− targeted agent was 4.0 (3.4–8.6) months (p = 0.012). CDK4/6i + AI as first-line treatment for HR-positive, HER2-negative MBC in Alberta is justified based on favourable PFS and early OS outcomes.

scholarly journals Sequential Treatment of Metastatic Adenocarcinoma of the Pancreatic Duct with Liver Metastasis Following the NAPOLI-1 Study Protocol with nal-Irinotecan plus 5-FU in the Second Line

2020 ◽  
Vol 13 (1) ◽  
pp. 79-84
Author(s):  
Dilara Akhoundova Sanoyan ◽  
Cäcilia S. Reiner ◽  
Panagiota Papageorgiou ◽  
Alexander R. Siebenhüner
Keyword(s):  
Systemic Treatment ◽  
Sequential Treatment ◽  
Phase Iii ◽  
Ductal Adenocarcinoma ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Curative Surgery ◽  
To Receive

Pancreatic ductal adenocarcinoma (PDAC) is typically diagnosed at an advanced or metastatic stage, when curative surgery is not recommended. Therefore, the prognosis is poor for this dismal disease, with only 1–2% of the patients reaching the 5-year survival follow-up. Current advances in systemic treatment with gemcitabine regimens, specifically polychemotherapy with gemcitabine plus nab-paclitaxel or other multidrug regimens such as FOLFIRINOX in the first line, have improved disease control over time. This higher efficacy of systemic treatment enables metastatic PDAC patients to receive second-line treatment more often nowadays. Currently, there is only one regimen for second-line treatment approved by the EMA, FDA, and Swissmedic, based on the phase III NAPOLI-1 study. In this case report, we present an outstanding response to sequential treatment with gemcitabine plus nab-paclitaxel followed by second-line treatment with nal-irinotecan plus 5-fluorouracil.

Video-Thoracoscopic Management of Postpneumonectomy Empyema

2018 ◽  
Vol 66 (08) ◽  
pp. 701-706 ◽  
Author(s):  
Lorenzo Spaggiari ◽  
Domenico Galetta
Keyword(s):  
Median Time ◽  
Thoracoscopic Surgery ◽  
Bronchopleural Fistula ◽  
Nonsmall Cell Lung Cancer ◽  
Invasive Approach ◽  
Thoracoscopic Approach ◽  
Open Window ◽  
Open Window Thoracostomy ◽  
A Minor

Background Postpneumonectomy empyema (PPE) is a serious complication even when it is not associated with bronchopleural fistula (BPF). Besides irrigation, an aggressive treatment is usually applied for removing infected material. However, a minimally invasive approach might achieve satisfactory results in selected patients. Methods We retrospectively identified 18 patients presenting with PPE receiving video-thoracoscopic approach. Of these 18 patients, pneumonectomy was performed for nonsmall cell lung cancer in 15 cases, for mesothelioma in 2, and for trauma in 1 case. There were 14 males and 4 females, (mean age, 62 years; range, 44–73 days). Empyema was confirmed by thoracentesis and bacteriological examination. All patients had immediate chest tube drainage and underwent thoracoscopic debridement of the empyema. Fifteen patients had no proven BPF; two had suspicious BPF, and one had a minor (<3 mm) BPF. Results Median time from pneumonectomy to empyema diagnosis was 129 days (range, 7–6205 days). Median time from drain position to video-assisted thoracoscopic surgery (VATS) procedure was 10 days (range, 2–78 days). A bacterium was isolated in 13 cases (72.2%). There was no mortality and no morbidity related to the procedure. The average duration of thoracoscopic debridement was 56 minutes (range, 40–90 minutes). Median postoperative stay was 7 days (range, 6–18 days). Only in one patient an open-window thoracostomy was performed. Median follow-up of the 18 patients receiving thoracoscopy was 41.5 months (range, 1–78 months). None had recurrent empyema. The patient with a minor BPF remained asymptomatic and is doing well at 48 months follow-up. Conclusions Thoracoscopy might be a valid approach for patients presenting with PPE with or without minimal BPF. Video-thoracoscopic debridement of postpneumonectomy space is an efficient method to treat PPE.

Characteristics, treatment patterns, and economic burden of patients with metastatic cervical cancer receiving systemic anticancer therapy.

2021 ◽  
Vol 39 (28_suppl) ◽  
pp. 51-51
Author(s):  
Xiaoyun Pan ◽  
Lincy S. Lal ◽  
John White ◽  
Seyed Hamidreza Mahmoudpour ◽  
Christian Valencia
Keyword(s):  
Cervical Cancer ◽  
Economic Burden ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Duration Of Treatment ◽  
Second Line Therapy ◽  
Treatment Regimens ◽  
Line Therapy

51 Background: In 2021, 14,480 patients are estimated to be diagnosed with cervical cancer in the US; 16% of patients are expected to have metastatic disease for whom the 5-year survival rate is 17.6% per SEER estimates. Patients with metastatic cervical cancer (mCC) are treated mainly with systemic therapy. This study aims to describe the clinical characteristics, demographics, treatment patterns, and economic burden of patients with mCC receiving systemic therapy. Methods: Eligible women had been diagnosed with cervical cancer, as evidenced by >2 outpatient or >1 inpatient claim in the Optum Research Database from January 2014 through January 2020. Patients were included if they had metastasis within 6 months before or after cervical cancer diagnosis, with evidence of systemic treatment on or after the latter of a claim date for cervical cancer disease or metastatic disease. The index date was the first-line treatment initiation date. Patients were required to have ≥6 months of pre-index continuous enrollment. The top 3 treatment regimens and median treatment duration by line of therapy were described. All-cause per-patient-per-month (PPPM) costs (2019 US dollars), including plan and patient paid amounts, were reported for full follow-up period from first-line and second-line therapy initiation. Results: The study sample consisted of 778 patients (mean age, 59 years; commercial, 58%; Medicare Advantage, 42%). The mean (median) follow-up period was 14 (9) months. Top baseline comorbidities were diseases of the urinary system (71%) and diseases of the female genital organs (70%), and the median Charlson comorbidity index was 7. In the first line, 80% of patients received platinum-based therapy and 23% received bevacizumab (bev). Of 778 patients, only 294 (38%) received second-line therapy, with 34% receiving bev. Top first-line treatment regimens were carboplatin + paclitaxel (27%), cisplatin (21%), and bev + carboplatin + paclitaxel (10%); the median (95% CI) duration of treatment was 3.4 (3.1-3.7) months. Top second-line treatment regimens were bev + carboplatin + paclitaxel (13%), carboplatin + paclitaxel (11%), and pembrolizumab (6%); the median duration of treatment was 3.8 (3.1-4.2) months. Mean all-cause total PPPM costs were $19,519 from first-line and $22,660 second-line therapy initiation (table). Conclusions: This study indicates that real-world mCC patients have short treatment durations and significant economic burden with first-line and second-line therapy. Novel therapies associated with greater clinical benefits in patients with mCC may provide economic benefit.[Table: see text]

Efficacy of cetuximab after immunotherapy (IO) in advanced cutaneous squamous cell carcinoma (CSCC).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9562-9562
Author(s):  
Julian Andres Marin-Acevedo ◽  
Bethany Withycombe ◽  
Youngchul Kim ◽  
Zeynep Eroglu ◽  
Joseph Markowitz ◽  
...  
Keyword(s):  
Locally Advanced ◽  
Acquired Resistance ◽  
Standard Of Care ◽  
Line Treatment ◽  
Second Line ◽  
Survival Times ◽  
Entire Cohort ◽  
Overall Response ◽  
Curative Radiotherapy

9562 Background: Anti-PD1 (aPD1) monotherapy with cemiplimab-rwlc or pembrolizumab is now considered standard of care for first-line management of advanced CSCC not amenable to surgery or curative radiotherapy. Previously chemotherapy or anti-EGFR agents were commonly used for these patients albeit with modest efficacy and limited duration of response. In prospective evaluation, the overall response rate (ORR) to cetuximab was 28% with disease control rate (DCR) of 69% at 6 weeks. The efficacy of second-line treatment following primary or acquired resistance to aPD1 therapy is not known. We investigated the activity of cetuximab in patients who progressed on previous IO therapy. Methods: We performed a single institution retrospective review from 9/28/18 (US approval date of cemiplimab-rwlc for CSCC) through 11/30/20 of patients with locally advanced or metastatic CSCC who received cetuximab after prior IO therapy. We identified patients who received cetuximab either immediately following IO therapy (cohort A) or as a subsequent line not immediately following IO therapy (cohort B). Primary endpoint was ORR with secondary endpoints of DCR, survival and toxicity. Median follow-up and survival times were calculated using the Kaplan-Meier method. Results: Thirteen patients, median age 72 years (62-82), all Caucasian, and 11 males (85%) were included in this study. Eleven pts received cetuximab immediately post-IO progression; two had additional intervening therapy post-IO before receiving cetuximab. Three patients received concurrent radiotherapy (palliative or definitive) with cetuximab. The ORR to cetuximab was 54% (7/13) including 1 complete and 6 partial responses. The cumulative 6-month DCR was 77%. All responses were observed in cohort A; both patients in cohort B had progressive disease as best response. Six of 7 initial responses are ongoing, including 3 in whom cetuximab was discontinued. At a median follow-up of 9.1 months, the median PFS has not been reached for the entire cohort. There were no unanticipated toxicities to cetuximab with rash (77%) and hypomagnesemia (54%) being the most common adverse events. Conclusions: In advanced CSCC, cetuximab used immediately after progression on aPD1 therapy yields notably higher and durable overall response than previously reported in the pre-IO therapy era. If validated in a larger dataset, this should be the preferred therapy for second-line treatment in advanced CSCC. Further exploration into the mechanism of this high efficacy of anti-EGFR therapy post aPD1 therapy is warranted.

Comparison of treatment options in adults with frequently relapsing or steroid-dependent minimal change disease

2020 ◽  
Author(s):  
Cihan Heybeli ◽  
Stephen B Erickson ◽  
Fernando C Fervenza ◽  
Marie C Hogan ◽  
Ladan Zand ◽  
...  
Keyword(s):  
Median Time ◽  
Minimal Change Disease ◽  
Treatment Options ◽  
Calcineurin Inhibitors ◽  
Immunosuppressive Drugs ◽  
Minimal Change ◽  
Line Treatment ◽  
Second Line ◽  
Steroid Dependent ◽  
Time To Relapse

Abstract Background Studies comparing all treatment options for frequently-relapsing/steroid-dependent (FR/SD) minimal change disease (MCD) in adults are lacking. Methods Medical records of 76 adults with FR/SD MCD who were treated with corticosteroids as the first-line therapy were reviewed. Treatment options were compared for the time to relapse, change of therapy and progression (relapse on full-dose treatment). Results Second-line treatments included rituximab (RTX; n = 13), mycophenolate mofetil (MMF; n = 12), calcineurin inhibitors (CNI; n = 26) and cyclophosphamide (CTX; n = 16). During the second-line treatments, 48 (71.6%) patients relapsed at median 17 (range 2–100)  months. The majority of relapses occurred during dose tapering or off drug. Twenty of 65 (30.8%) changed therapy after the first relapse. The median time to relapse after the second line was 66 versus 28 months in RTX versus non-RTX groups (P = 0.170). The median time to change of treatment was 66 and 44 months, respectively (P = 0.060). Last-line treatment options included RTX (n = 8), MMF (n = 4), CNI (n = 3) and CTX (n = 2). Seven (41.2%) patients had a relapse during the last-line treatment at median 39 (range 5–112)  months. The median time to relapse was 48 versus 34 months in the RTX versus non-RTX groups (P = 0.727). One patient in the RTX group died presumably of heart failure. No major adverse event was observed. During the median follow-up of 81 (range 9–355)  months, no patients developed end-stage renal disease. Conclusions Relapse is frequent in MCD in adults. Patients treated with RTX may be less likely to require a change of therapy and more likely to come off immunosuppressive drugs.

scholarly journals Urothelial Proliferation of Unknown Malignant Potential Involving the Bladder: Histopathologic Features and Risk of Progression in De Novo Cases and Cases With Prior Neoplasia

2019 ◽  
Vol 144 (7) ◽  
pp. 853-862
Author(s):  
Brett M. Lowenthal ◽  
Debashis Sahoo ◽  
Mahul B. Amin ◽  
Donna E. Hansel
Keyword(s):  
Median Time ◽  
De Novo ◽  
Clinical Findings ◽  
Malignant Potential ◽  
World Health ◽  
Time To Progression ◽  
Risk Of Progression ◽  
Health Organization ◽  
Subsequent Risk

Context.— Urothelial proliferation of unknown malignant potential (UPUMP) is a 2016 World Health Organization classifier that encompasses prior categories of flat and papillary urothelial hyperplasia. In addition, UPUMP occurs in settings of both de novo and prior bladder neoplasia. Objective.— To identify UPUMP features associated with subsequent neoplastic development. Design.— Sixty-eight patients were identified from the archives, including 26 patients with de novo and 42 patients with prior bladder neoplasia. Patient slides and clinical course were reviewed. Results.— Patients with de novo UPUMP were detected through clinical findings (26/26; 100%), whereas surveillance cystoscopy primarily detected UPUMP in patients with prior neoplasia (29/42; 69%). Histopathologic criteria evaluated included urothelial hyperplasia, urothelial cytology, vascular ingrowth, denudation, inflammation, edema, and fibrosis. Mean clinical follow-up was 68.9 months in patients with de novo neoplasia and 69.5 months in patients with prior neoplasia. Subsequent neoplasia developed in 4 of 26 (15.4%) of patients with de novo UPUMP and was associated with cystoscopic papillary appearance (P = .02) or microscopic thin papillary ingrowths or papillations (P = .02; median time to progression, 4.1 months). Of 42 patients with prior neoplasia, 17 (40.5%) had subsequent neoplasia, significantly associated with an absence of prominent lamina propria edema (P &lt; .001; median time to progression, 11.0 months). A higher rate of progression to high-grade disease was present in patients with a prior neoplasia versus those with de novo disease (58.9% versus 25%). Conclusions.— Urothelial proliferation of unknown malignant potential shows subsequent risk of neoplastic development of 17% in patients with de novo disease and 40% in patients with prior neoplasia. The greatest risk of progression is associated with early papillary formation.

Sign in / Sign up

Export Citation Format

Share Document