Pomalidomide (Pom) in Relapsed and Refractory Multiple Myeloma (RRMM) - theUARK Compassionate Use Protocol,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3995-3995
Author(s):  
Saad Usmani ◽  
Sarah Waheed ◽  
Jackie Szymonifka ◽  
Susan Panozzo ◽  
Nathan M Petty ◽  
...  
Keyword(s):  
Research Funding ◽  
Cox Regression ◽  
Univariate Analysis ◽  
Progression Free Survival ◽  
Autologous Stem Cell Transplant ◽  
Cell Transplant ◽  
Compassionate Use ◽  
Free Survival ◽  
Kaplan Meier ◽  
Grade 3

Abstract Abstract 3995 Background: Pom is a third generation immunomodulatory drug (IMiD) which has demonstrated safety and efficacy in RRMM with prior exposure/resistant to other IMiDs and bortezomib. This is the first report on the UARK Pom compassionate use experience in RRMM. Methods: First cycle Pom was given at 4mg orally Days 1–21 every 28 days; dexamethasone (DEX) was given to 9/23 patients at doses varying from 12 to 40 mg on schedules ranging from Days 1–4, weekly, twice a week, or three times a week. In the absence of at least PR, Pom dose was escalated to 5mg. 1patient also received bortezomib and 1 patient received bortezomib and cytoxan. Cox regression modeling was employed for univariate and multivariate analyses, whereas Kaplan-Meier curves were used for overall survival (OS) and progression free survival (PFS). Results: 23 patients with RRMM were enrolled. Baseline characteristics included age >=65yr in 43%, ISS stage >=II was seen in 78% of patients, cytogenetic abnormalities (CA) within 6 months in 80%, and GEP-defined high risk in 41% of patients. 22/23 patients (96%) had prior autologous stem cell transplant. 19/23 patients (83%) had at least 2 transplants. All 23 patients had disease progression after having received regimens containing bortezomib, thalidomide, lenalidomide, melphalan and steroids. At least 1 cycle of treatment was administered to all 23 patients enrolled, 52% of patients received >1 cycle of treatment and only 13% received =>5 cycles. 10 patients (43%) discontinued therapy primarily due to progression or death. 5/23 (22%) patients achieved PR, 57% had stable disease. A trend towards PFS benefit was observed in patients receiving cycle 2 (HR=0.30, p=0.215) on univariate analysis and multivariate analysis (HR=0.40, p=0.48) after adjusting for GEP-defined risk status (HR=2.69, p=0.16). Most common toxicities, counting all toxicities (>=grade 3) were: thrombocytopenia (70%), leukopenia (61%), anemia (43%), hypophosphatemia (35%) and hypokalemia (26%). Overall and progression- free survival at 12 months were 52% and 30%, respectively. Conclusions: Pom demonstrates anti-myeloma activity in this advanced RRM population, especially in a sub-population with GEP-defined low-risk disease. Disclosures: Barlogie: Celgene: Consultancy, Honoraria, Research Funding; IMF: Consultancy, Honoraria; MMRF: Consultancy; Millennium: Consultancy, Honoraria, Research Funding; Genzyme: Consultancy; Novartis: Research Funding; NCI: Research Funding; Johnson & Johnson: Research Funding; Centocor: Research Funding; Onyx: Research Funding; Icon: Research Funding.

Phase II Study of Carfilzomib (CFZ) Combined with Other Anti-Myeloma Agents in Relapsed-Refractory Multiple Myeloma (RRMM) - Updates on the UARK Compassionate Use Protocol

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2947-2947 ◽  
Author(s):  
Saad Usmani ◽  
Jackie Szymonifka ◽  
Rachael Sexton ◽  
Susan Panozzo ◽  
Bijay Nair ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Phase Ii ◽  
Research Funding ◽  
Cox Regression ◽  
Phase Ii Study ◽  
Univariate Analysis ◽  
Cell Transplant ◽  
Compassionate Use ◽  
Refractory Multiple Myeloma ◽  
Grade 3

Abstract Abstract 2947 Background: CFZ is an epoxomicin derivative with ability to irreversibly inhibit proteosomes. It has been shown in preclinical and early clinical studies to have activity in newly diagnosed as well as RRMM. We have previously reported on the UARK compassionate use phase II study of CFZ which allowed for the addition of other anti-MM drugs in RRMM. We are now presenting data with 7 additional patients and longer follow-up, with data cut-off on August 9 2011. Methods: All patients with relapsed or resistant refractory multiple myeloma were eligible for the trial. First cycle CFZ was given at 20mg/m2 IV day 1, 2, then 27mg/m2 IV days 8, 9, 15, 16 every 28 days; 4mg of dexamethasone (DEX) was given with each CFZ dose. In the absence of at least PR, CFZ dose was escalated to 36 mg/m2 IV and DEX increased to 20mg. Additional anti-myeloma drugs were added Cycle 2 onwards in absence of PR. 16-day continuous infusion cisplatin (3–5 mg/m2/d) and doxorubicin (1.5–3 mg/m2/d) were commonly added from Cycle 2 onwards, along with other novel agents. Cox regression modeling was employed for overall survival (OS) and progression free survival (PFS). Results: 81 patients with RRMM were enrolled. Baseline characteristics included age >=65yr in 32%, ISS stage >=II was seen in 72% of patients, cytogenetic abnormalities (CA) in 68%, and GEP-defined high risk in 53% of patients. 77 patients had prior autologous stem cell transplant. 63 patients (78%) had at least 2 transplants. All 81 patients had received regimens containing bortezomib, thalidomide, lenalidomide, melphalan or steroids. At least 1 cycle of treatment was administered to all 81 patients enrolled, 69% of patients received >1 cycle of treatment and only 19% received >5 cycles. 71 patients (88%) discontinued therapy primarily due to progression, death or toxicity. 5% patients achieved nCR/CR/sCR, additional 19% patients had stable disease. OS benefit was observed in patients receiving >= cycle 3 (HR= 0.40, p=0.006) on univariate analysis and multivariate analysis (HR=0.09, p<0.001) with adjustment for GEP-defined risk status. Most common toxicities, counting all toxicities (>=grade 3) were thrombocytopenia (84%), anemia (77%), leukopenia (73%), hypophosphatemia (58%), hypokalemia (27%) and fatigue (25%). Grade 1–2 peripheral neuropathy (PN) was present at baseline in 53%, >grade 3 PN was observed in 7% (6/81) after cycle 1, whereas >grade 3 PN was observed in 8% (1/12) >5 cycles.OS and PFS at 12 months were 41% and 5%, respectively (Figure 1). Conclusions: The data presented herein, confirm and extend the previously reported results on CFZ demonstrating anti-myeloma activity and clinical benefit, alone and in combination with other agents, in our heavily pre-treated RRMM population. Surprisingly, worsening or new PN was not observed in majority of patients. Utilizing the novel proteasome inhibitor CFZ in combination with other anti-MM agents on a compassionate basis afforded us the opportunity to make observations regarding potential clinical synergy of particular combinations. In particular, combination of CFZ-DEX with lenalidomide and vorinostat has shown promise in a subset of RRMM patients. Disclosures: Barlogie: Celgene: Consultancy, Honoraria, Research Funding; IMF: Consultancy, Honoraria; MMRF: Consultancy; Millennium: Consultancy, Honoraria, Research Funding; Genzyme: Consultancy; Novartis: Research Funding; NCI: Research Funding; Johnson & Johnson: Research Funding; Centocor: Research Funding; Onyx: Research Funding; Icon: Research Funding.

Retrospective analysis of ipilimumab-induced diarrhea and/or colitis: A single centre review.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e21064-e21064 ◽  
Author(s):  
Marco Adelmo James Iafolla ◽  
Gregory Russell Pond ◽  
Elaine McWhirter
Keyword(s):  
Cox Regression ◽  
Univariate Analysis ◽  
Progression Free Survival ◽  
Published Data ◽  
Free Survival ◽  
Severe Diarrhea ◽  
Patient Demographics ◽  
Kaplan Meier ◽  
Melanoma Patients ◽  
Grade 3

e21064 Background: Ipilimumab is an effective medication in advanced melanoma but can cause severe diarrhea and colitis. This study identified the rate of ipilimumab-induced diarrhea/colitis at the Juravinski Cancer Centre (JCC), its associated factors for development, overall survival (OS) and progression free survival (PFS). Methods: The Ontario Patient Information System was used to retrospectively identify all melanoma patients at the JCC who were treated with ipilimumab 3 mg/kg IV every 3 weeks (September 2012 to June 2016). Patient demographics, medical history, prior melanoma treatments, diagnosis of ipilimumab-induced diarrhea/colitis, interventions to treat the diarrhea/colitis, and OS and PFS were collected. Descriptive statistics summarized characteristics and outcomes. Kaplan-Meier methods estimated time to event outcomes. Cox regression evaluated whether markers were prognostic for time to diarrhea/colitis diagnosis. Results: 71 patients were treated with ipilimumab at the JCC, of which 22 patients (31%) developed diarrhea/colitis of any Grade; 4 patients developed Grade 1, 5 patients Grade 2, 6 patients Grade 3, 3 patients Grade 4, and 4 patients had unclear Grade. 11 patients required prednisone 1-2 mg/kg and 2 patients required anti-TNF treatment to treat their diarrhea/colitis; 1 patient required colectomy due to perforation. 10 patients required treatment discontinuation due to diarrhea/colitis. Whole cohort median OS and PFS was 340 days (95% CI 205, 519) and 110 days (95% CI 91, 138), respectively. Univariate analysis showed that only inadequate hematologic function at time of first ipilimumab application was prognostic of diarrhea/colitis (HR = 6.42, 95% CI 1.44, 28.62; p = 0.015). Conclusions: Our OS, PFS, and rate of all grade ipilimumab-induced diarrhea/colitis are similar to published data, however our rate of Grade > 2 is larger. Additional work is needed to identify risk factors for the development of this immune related adverse event.

scholarly journals Response and Toxicity to the Second Course of 3 Cycles of 177Lu-PSMA Therapy Every 4 Weeks in Patients with Metastatic Castration-Resistant Prostate Cancer

Cancers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2489
Author(s):  
Sazan Rasul ◽  
Tim Wollenweber ◽  
Lucia Zisser ◽  
Elisabeth Kretschmer-Chott ◽  
Bernhard Grubmüller ◽  
...  
Keyword(s):  
Response Rate ◽  
Cox Regression ◽  
Progression Free Survival ◽  
Castration Resistant Prostate Cancer ◽  
Radioligand Therapy ◽  
Free Survival ◽  
Castration Resistant ◽  
Kaplan Meier ◽  
Node Metastases ◽  
Grade 3

Background: We investigated the response rate and degree of toxicity of a second course of three cycles of [177Lu]Lu-PSMA radioligand therapy (PSMA-RLT) every 4 weeks in mCRPC patients. Methods: Forty-three men (71.5 ± 6.6 years, median PSA 40.8 (0.87–1358 µg/L)) were studied. The response was based on the PSA level 4 weeks after the third cycle. The laboratory parameters before and one month after the last cycle were compared. Kaplan–Meier methods were used to estimate the progression-free survival (PFS) and overall survival (OS), and the Cox regression model was performed to find predictors of survival. Results: Twenty-six patients (60.5%) exhibited a PSA reduction (median PSA declined from 40.8 to 20.2, range 0.6–1926 µg/L, p = 0.002); 18 (42%) and 8 (19%) patients showed a PSA decline of ≥50% and ≥80%, respectively. The median OS and PFS were 136 and 31 weeks, respectively. The patients with only lymph node metastases survived longer (p = 0.02), whereas the patients with bone metastases had a shorter survival (p = 0.03). In the multivariate analysis, only the levels of PSA prior to the therapy remained significant for OS (p < 0.05, hazard ratio 2.43, 95% CI 1.01–5.87). The levels of hemoglobin (11.5 ± 1.7 g/dL vs. 11 ± 1.6 g/dL, p = 0.006) and platelets (208 ± 63 g/L vs. 185 ± 63 g/L, p = 0.002) significantly decreased one month after cycle three, though only two grade 3 anemia and one grade 3 thrombocytopenia were recorded. Conclusion: A further intensive PSMA-RLT course is well tolerated in mCRPC patients and associated with promising response rates and OS.

In the Era of Bortezomib-Based Chemotherapy the Presence of Minimal Residual Disease Predicts Progression Free Survival after Autologous Hematopoietic Cell Transplant

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5493-5493
Author(s):  
Robert F Cornell ◽  
Jade E Jones ◽  
Claudio A. Mosse ◽  
Heidi Chen ◽  
Laura Dugger ◽  
...  
Keyword(s):  
Induction Chemotherapy ◽  
Induction Therapy ◽  
Research Funding ◽  
Residual Disease ◽  
Progression Free Survival ◽  
Cell Transplant ◽  
Hematopoietic Cell Transplant ◽  
Free Survival ◽  
Kaplan Meier ◽  
Minimal Residual

Abstract Background: Retrospective studies have shown that achieving minimal residual disease (MRD) by multi-parameter flow cytometry (MFC) is predictive of outcomes in multiple myeloma (MM). Modern induction therapies including bortezomib (V), lenalidomide (R) followed by autologous hematopoietic cell transplant (AHCT) have resulted in substantial improvements in progression free survival (PFS) and overall survival (OS). The impact of bortezomib-based therapy on end of induction chemotherapy MRD status and post-AHCT MRD status is not well defined. We designed a prospective clinical trial (NCT01215344) to study the incidence of MRD negativity at end of induction and following AHCT, and its association with PFS and OS. Patients and Methods: Twenty patients with newly diagnosed, symptomatic MM were enrolled. They received four cycles of VRd induction therapy followed by AHCT. Dose modifications of VRd were controlled during the clinical trial. MRD status by MFC was evaluated at the end of induction chemotherapy and at day 100 post-AHCT. The MFC cut-off to determine MRD negativity was defined as 10-4. Outcomes analyzed included MM disease status, PFS and OS. Results: Three cohorts of patients were identified; patients achieving MRD negative status at the end of induction (cohort 1, 50%), those achieving MRD negative status only after AHCT (cohort 2, 15%) and patients never achieving MRD negative status (cohort 3, 35%). All patients achieving MRD negative status at the end of induction remained MRD negative post-AHCT. There were no significant differences in median age, renal function, disease stage, cytogenetic risk and maintenance chemotherapy post-AHCT between cohorts. The table summarizes characteristics of these cohorts. Patients who never achieved MRD negative status after AHCT had significantly shorter PFS (cohort 3) compared with patients who achieved MRD negative status (cohorts 1 and 2, p=0.008) (figure). The median PFS for cohort 3 was 2.64 years and not yet reached for the other cohorts. There were no significant differences in OS. Median follow-up for survivors was 2.53 years (range, 0.73-4.04). Conclusions: In this study, bortezomib-based therapy resulted in half of patients achieving MRD negative status with induction chemotherapy alone. AHCT improved the depth of response with 30% of patients who were MRD positive after induction therapy converting to MRD negativity following AHCT. Achieving a negative MRD state, pre- and at D100 post-AHCT resulted in improved PFS. These findings were independent of molecular cytogenetics or ISS stage. MRD positive status at day 100 post-AHCT is highly predictive of earlier disease progression, and may help identify patients for alternative management approaches. Delay of AHCT may be considered as a potential management option for patients with MRD negative status at the end of induction therapy, as being studied in the IFM DFCI study (NCT01208662). As some patients with MRD positive disease at the end of induction therapy become MRD negative with AHCT, these patients may benefit from AHCT and this population warrants further investigation. Table. Descriptive analysis Cohort 1 MRD -/- (%) (n=10) Cohort 2 MRD +/- (%) (n=3) Cohort 3 MRD +/+ (%) (n=7) Test Statistic Median Age 55 54 60 0.31 ISS Stage III 40 33 14 0.52 DS Stage III 89 67 60 0.14 Median Serum creatinine 0.90 0.60 0.88 0.10 Serum M-spike 2.0 1.9 2.1 0.80 Bone marrow plasma cells 14 44 14 0.18 Cytogenetics 0.37 Standard risk 40 0 57 Intermediate risk 50 67 43 High risk 10 33 0 Figure 1. Kaplan-Meier curve of progression-free survival comparing patients achieving MRD negative disease with MRD positive disease. Figure 1. Kaplan-Meier curve of progression-free survival comparing patients achieving MRD negative disease with MRD positive disease. Disclosures Cornell: Prothena: Research Funding. Jagasia:Takeda Inc: Research Funding.

scholarly journals Optimal Therapy for Relapsed AL Amyloidosis Post Autologous Stem Cell Transplant

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3171-3171
Author(s):  
M Hasib Sidiqi ◽  
Abdullah S. S. Al Saleh ◽  
Iuliana Vaxman ◽  
Angela Dispenzieri ◽  
Francis K. Buadi ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Research Funding ◽  
Progression Free Survival ◽  
Autologous Stem Cell Transplant ◽  
Al Amyloidosis ◽  
Cell Transplant ◽  
Advisory Committees ◽  
Free Survival ◽  
Treatment Regimens ◽  
2Nd Generation

Introduction: There is a paucity of randomized trials to guide therapy for relapsed AL amyloidosis with treatment regimens generally extrapolated from experience in multiple myeloma. Methods: We conducted a retrospective review of patients who relapsed after receiving autologous stem cell transplant at Mayo Clinic. Patients treated for first relapse between January 2004 and December 2018 were included. Results: Three hundred and twenty-one patients were seen for relapsed AL amyloidosis post ASCT during the study period. Baseline characteristics were typical for a cohort with AL amyloidosis and are listed in Table1. 39% received therapy prior to transplant, conditioning in the majority (75%) was melphalan 200mg/m2. The median progression free survival from transplant (PFS1) was 30.7 months. Of the 321 patients 294 received treatment for relapsed disease. We categorized treatment regimens according to commonly used combinations and drug classes to further analyze outcomes. 34 patients were excluded from this analysis as they either proceeded directly to second ASCT (n=10) or received an atypical regimen not commonly considered for AL amyloidosis (n=24). Five categories of therapy regimens were identified, thalidomide based (n=110), melphalan plus steroids (n=31), 2nd generation immunomodulatory (IMiD) drug +/- alkylator (n=76), proteasome inhibitor (PI) +/- alkylator (n=116), PI plus IMiD (n=16), or daratumumab based (n=9). Disease and treatment characteristics for patients treated with these regimens are listed in Table 2. Patients treated with thalidomide had the shortest PFS1 (17.7 months) but PFS1 was similar for those treated with melphalan plus steroids, PI+IMiD and 2nd generation IMiDs (25.5, 24.3 and 25.6 months respectively). Patients treated with a PI +/- alkylator and daratumumab based regimen had the longest PFS1 (36.7 and 41.9 months respectively). The median duration of therapy was longer in patients treated with a 2nd generation IMiD or daratumumab based regimen (10.2, 12, 6.1, 5.5, 6.2 and 5.9 months for Dara based, 2nd generation IMiD, PI+/- alkylator, PI+IMiD, melphalan plus steroids and thalidomide based respectively). Hematologic response rate was lowest in those treated with melphalan plus steroids or thalidomide based regimens (44% and 55% respectively) and highest for patients treated with a PI+/- alkylator, (Figure 1). Progression free survival from relapsed therapy (PFS2) was longest amongst patients treated with daratumumab based regimens, PI +/- alkylator and 2nd generation IMiDs (not reached, 29.9 and 26.7 months respectively), Figure 2A. Overall survival from time of relapsed therapy favored patients treated with daratumumab based regimens, 2nd generation IMiDs and PI +/- alkylator, Figure 2b). Conclusion: A second generation IMiD based regimen or PI +/- alkylator produce high response rates and prolonged progression free and overall survival for relapsed AL amyloidosis. Patients treated with daratumumab based regimens and those treated with a PI plus IMiD also appear to do well, although numbers were low in our study. Patients treated with melphalan plus steroids or thalidomide based combinations have inferior outcomes and these regimens should be avoided. Disclosures Dispenzieri: Celgene: Research Funding; Takeda: Research Funding; Pfizer: Research Funding; Janssen: Consultancy; Intellia: Consultancy; Akcea: Consultancy; Alnylam: Research Funding. Lacy:Celgene: Research Funding. Dingli:Karyopharm: Research Funding; Rigel: Consultancy; Millenium: Consultancy; Janssen: Consultancy; alexion: Consultancy. Leung:Takeda: Research Funding; Prothena: Membership on an entity's Board of Directors or advisory committees; Aduro: Membership on an entity's Board of Directors or advisory committees; Omeros: Research Funding. Kapoor:Glaxo Smith Kline: Research Funding; Sanofi: Consultancy, Research Funding; Celgene: Honoraria; Cellectar: Consultancy; Amgen: Research Funding; Takeda: Honoraria, Research Funding; Janssen: Research Funding. Kumar:Takeda: Research Funding; Celgene: Consultancy, Research Funding; Janssen: Consultancy, Research Funding. Gertz:Medscape: Consultancy, Speakers Bureau; Prothena Biosciences Inc: Consultancy; Ionis/Akcea: Consultancy; Alnylam: Consultancy; Celgene: Consultancy; Janssen: Consultancy; Spectrum: Consultancy, Research Funding; Appellis: Consultancy; Amgen: Consultancy; Physicians Education Resource: Consultancy; Abbvie: Other: personal fees for Data Safety Monitoring board; Research to Practice: Consultancy; Teva: Speakers Bureau; Johnson and Johnson: Speakers Bureau; DAVA oncology: Speakers Bureau; Pharmacyclics: Membership on an entity's Board of Directors or advisory committees; Proclara: Membership on an entity's Board of Directors or advisory committees; i3Health: Other: Development of educational programs and materials; Springer Publishing: Patents & Royalties; Amyloidosis Foundation: Research Funding; International Waldenstrom Foundation: Research Funding; Annexon: Consultancy. OffLabel Disclosure: Daratumumab off label use for AL amyloidosis.

Very Good Partial Response and Complete Response Predict Superior Overall Survival and Progression Free Survival After Single Autologous Stem Cell Transplant in Patients with Multiple Myeloma,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4111-4111
Author(s):  
Victor H Jimenez-Zepeda ◽  
Donna E. Reece ◽  
Suzanne Trudel ◽  
Christine Chen ◽  
Andrew Winter ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Research Funding ◽  
Progression Free Survival ◽  
Complete Response ◽  
Autologous Stem Cell Transplant ◽  
Novel Agents ◽  
Cell Transplant ◽  
Free Survival ◽  
The Impact

Abstract Abstract 4111 In multiple myeloma (MM), the impact of complete response (CR) and very good partial response (VGPR) achievement has been shown mostly after introduction of high dose therapy (HDT) supported by autologous stem cell transplant (ASCT). Recently, the IFM group reported the impact of achievement of CR and VGPR in double ASCT. The purpose of this study is to confirm the prognostic value of CR/VGPR in a large group of patients treated with single ASCT. Methods All consecutive patients who underwent single ASCT at Princess Margaret Hospital between January 2000 and December 2007 were evaluated. Patients were mobilized with cyclophosphamide and G-CSF and majority were conditioned with melphalan 200mg/m2. Response to therapy was assessed according to the IMWC including VGPR. Progression Free Survival (PFS) and Overall Survival (OS) were measured from transplant date to the date of death or last follow-up. OS and DFS were analyzed using the Kaplan-Meier Method. The Cox proportional hazard model was used to assess CR and VGPR and some other prognostic markers at presentation such as age, B2Mg> 460 μmol/L, LDH> 350 IU/L, CRP> 20mg/L, albumin<35g/L and creatinine > 200 μmol/L. All p-values were 2-sided and statistically significant if <0.05. Results 788 patients were identified for the study; their median age was 56 years (30–73). Patient's characteristics are listed in Table 1. Response was assessed at day 100 after ASCT and showed a CR of 6%, PR of 37.5%, and VGPR of 53% (Overall Response rate of 95.5%). Median OS and PFS for the group were 77.43 months and 20.63 months respectively. The median OS and PFS were significantly better for patients who achieved CR/VGPR, 104.5 months versus 51.7 months, and 26.3 months versus 13.53 months respectively. With a median follow-up of 44 months there is no significant difference in OS for those patients who achieved VGPR/CR after induction therapy with novel agents. However, PFS is better in those patients receiving novel agents who achieved VGPR/CR (Median PFS of 24.63months versus 12.4 months respectively (p=0.01). Multivariate analysis shows CR/VGPR as an independent prognostic factor for OS and PFS (Fig 1 and 2). B2Mg> 460 μmol/L, LDH> 350 IU/L, CRP > 20mg/L, albumin<35g/L and creatinine > 200 μmol/L failed to be important factor for survival in the multivariate analysis. Our data suggests that VGPR/CR is clearly important in the pre-novel agents era and for the smaller group of patients who had novel agents induction there is a benefit in PFS and with a longer follow-up perhaps in OS. In conclusion, VGPR/CR remains a simple and powerful indicator in the context of single ASCT and should be considered a relevant objective for MM treatment. Table 1. Clinical characteristics of patients with Multiple Myeloma undergoing single ASCT Clinical characteristic N=788 Median Range % Age (years) 58 31–74 Male 59.4% Female 40.6% Hemoglobin (g/L) 114 54–180 Creatinine (μmol/L) 107 28–1409 B2-microglobulin ((μmol/L) (N=718) 508 260–7270 Albumin (g/L) (N=650) 38 23–54 IgG 51.1% IgA 31.3% IgM 0.4% IgD 0.7% Biclonal 9.9% Not Detected 6.6 Kappa 59.4% Lambda 32.9% Biclonal 2% Not Detected 5.7% Calcium (μmol/L) 2.29 1.62–4.66 LDH (IU/L) (N=754) 235 50–1470 Induction Treatment: 52.2% VAD 22.8% Dexamethasone 6.3% TD 2.3% CP 3.8% DPACE/DTPACE 1.7% DVD 8% CyBORD 2% VD Ab: VAD: Vincristine, Adriamycin and dexamethasone, TD: Thalidomide and Dexamethasone; CP: Cyclophosphamide and Prednisone, DVD: Doxil, Velcade and Dexamethasone, CyBORD: Cyclophosphamide, Bortezomib and Dexamethasone and VD: Valcade and Dexamethasone Disclosures: Jimenez-Zepeda: J & J: Honoraria. Reece:Bristol, Meyers, Squibb: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Johnson&Johnson: Research Funding; Merck: Honoraria, Research Funding; Otsuka: Honoraria, Research Funding; Millennium: Research Funding; Amgen: Honoraria. Chen:Celgene Corporation: Consultancy, Honoraria, Research Funding. Kukreti:Celgene: Honoraria.

scholarly journals Transarterial Chemoembolization Followed by Radiotherapy Versus Sandwich Treatment for Unresectable or Ablative Hepatocellular Carcinoma

2020 ◽  
Vol 19 ◽  
pp. 153303382098379
Author(s):  
Haimin Lin ◽  
Huiyong Wu ◽  
Ning Cong ◽  
Bo Liu ◽  
Chengxin Liu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Transarterial Chemoembolization ◽  
Cox Regression ◽  
Progression Free Survival ◽  
Conformal Radiotherapy ◽  
Rank Test ◽  
Virus Reactivation ◽  
Free Survival ◽  
Kaplan Meier ◽  
Grade 3

Objective: Our objective is to assess whether the outcome of intrahepatic unresectable or ablative hepatocellular carcinoma (HCC) could be improved by supplemental transarterial chemoembolization (TACE) following initial treatment of TACE with 3-dimensional conformal radiotherapy (3DCRT), compared to TACE followed by 3DCRT alone. Methods: We retrospectively analyzed intrahepatic unresectable or ablative HCC patients who underwent TACE, followed by 3DCRT with or without additional TACE, from June 2010 to December 2016 at our institution. Survival was assessed using the Kaplan-Meier method and compared with the log-rank test. Cox regression analyses were used to identify factors that influenced prognosis. Toxicity profiles were evaluated using CTCAE 4.0. Results: 27 patients received TACE with 3DCRT (TR group) and 11 received additional TACE following TACE and 3DCRT (sandwich group), respectively. The median intrahepatic progression-free survival (IPFS), progression-free survival (PFS), and overall survival (OS) in the TR group and sandwich group were 5.4 months vs. 17 months (P = 0.018), 5.4 months vs. 17 months (P = 0.008), and 13.5 months vs. 29.2 months (P = 0.011), respectively. Multivariate Cox regression demonstrated that TACE followed by radiotherapy alone had a shorter IPFS (HR: 2.516, 95% CI (1.136-5.570), P = 0.023) and PFS (HR: 2.637, 95% CI (1.182-5.880), P = 0.018) compared with the sandwich treatment. Hepatitis B virus reactivation occurred in 1 patient in the sandwich group. Myleosuppresion was considered a grade 3/4 adverse event. Conclusion: Unresectable or ablative HCC patients possibly benefit from the combination of TACE and 3DCRT followed by additional TACE therapy, compared with TACE followed by 3DCRT alone.

Prediction of Progression-Free Survival with Brentuximab Vedotin Therapy for Relapsed Hodgkin Lymphoma: A Retrospective Analysis

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3086-3086
Author(s):  
Anna Houk ◽  
Ajay K. Gopal ◽  
Edward N. Libby ◽  
Andrei R. Shustov ◽  
Damian J. Green ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hodgkin Lymphoma ◽  
Confidence Intervals ◽  
Research Funding ◽  
Stem Cell Transplant ◽  
Progression Free Survival ◽  
Autologous Stem Cell Transplant ◽  
Brentuximab Vedotin ◽  
Cell Transplant ◽  
Free Survival

Abstract Introduction: The role of brentuximab vedotin (BV) in Hodgkin Lymphoma (HL) is expanding, but factors predicting progression-free survival (PFS) after BV therapy are poorly defined. Age, tumor bulk, presence of extranodal disease, neutrophil:lymphocyte ratio (ANC/ALC), and lymphocyte:monocyte ratio (ALC/AMC) predict outcome in HL patients (pts) treated with chemotherapy, but their impact on PFS after BV has not been well-studied. Also, among pts with relapsed/refractory HL (rel/ref HL) who progress after BV, efficacy of additional chemotherapy is undefined. To inform patient selection and future clinical trial design with BV, we undertook a retrospective study to identify factors predicting PFS with BV therapy in rel/ref HL, and explore chemotherapy efficacy as salvage after BV failure. Methods: Pts receiving BV since 2009 were identified through pharmacy and research records and studied with IRB approval. Those with rel/ref HL receiving BV before or after transplant without intervening therapy were excluded. Age ≥40 at time, sex, pre-BV PET findings (SUV max, extranodal [EN] involvement, bulk > 5cm), prior therapy (# lines of therapy> median; prior transplant, platinum-containing, radiotherapy), and lab findings (AMC/ALC³4.3, ALC/AMC ratio³1) at time of start of BV were examined for an impact on PFS and OS via log-rank testing of Kaplan-meier projections(JMP 11.0 software). PFS was defined as time from first BV dose to radiographic or clinical progression, initiation of post-BV salvage, or death from any cause. OS was measured from date of first BV dose to death from any cause. Efficacy of salvage therapy for those failing BV was recorded. Results: Of 90 patient receiving BV, 43 met above criteria. Median age was 34 yrs (range 17-80), median # of pre-BV therapies was 3 (range 1-7). 31 (73%) had failed autologous transplant, 10 (23%) had undergone allogeneic transplant, and 20 (46%) received radiotherapy prior to BV. Pre-BV PET staging data was available in 26 pts; post-BV PET was not analyzed in this dataset as response criteria were nonstandardized. BV was administered for a median 6 cycles (range 2-20). Median PFS after BV was 6 mo. (Figure 1) with 4 pts having PFS >4 yrs. At 31 mo. median follow-up, 71% of pts were alive with no plateau in the survival curve. On univariate analysis, age 40 or older at time of BV predicted inferior PFS (p=.03) and inferior OS though 95% confidence intervals were wide (OS by age: Figure 2, p=.02). HR for death for pts age 40 or older was 4 (98% CI .03-2.3, p=.05). No other factor predicted PFS or OS. Among 29 pts who failed BV, OS was 3.4 yrs. 40 chemotherapy regimens were given with 11 responses. Five of 11 pts responded to bendamustine, but median time to progression was 4 mo. Two of 4 responded to gemcitabine as did 3/8 receiving platinum chemotherapy. Conclusions: In this cohort of rel/ref HL pts treated with BV, PFS was 6 mo. overall and inferior among pts 40 yrs or older. OS was also worse in this group, although confidence intervals were wide in both univariate analyses. We confirm and expand upon prior data showing features predicting outcomes in HL after chemotherapy do not clearly apply after BV; and that most pts progress <1 year after single-agent BV with a few durable remissions. Salvage chemotherapy after BV has transient efficacy. Larger studies defining clinical, biologic, and PET-based markers of outcome after BV are needed. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures Off Label Use: Brentuximab is approved in HL after failure of autologous stem cell transplant; in this series, some patients received Brentuximab before or when ineligible for an autologous stem cell transplant.. Gopal:Seattle Genetics: Consultancy, Honoraria, Research Funding, Speakers Bureau; Takeda: Honoraria, Research Funding, Speakers Bureau; Janssen: Research Funding; Pfizer: Consultancy, Research Funding; BMS: Research Funding; Gilead: Research Funding; Spectrum: Research Funding; Teva: Research Funding. Shustov:Seattle Genetics, Inc.: Research Funding.

scholarly journals FAS and Subsequent Therapies in Pancreatic Neuroendocrine Tumors

2021 ◽  
Author(s):  
Jane E. Rogers ◽  
Michael Lam ◽  
Daniel M. Halperin ◽  
Cecile G. Dagohoy ◽  
James C. Yao ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Cox Regression ◽  
Progression Free Survival ◽  
Pancreatic Neuroendocrine Tumors ◽  
Free Survival ◽  
Prior Therapy ◽  
Well Differentiated ◽  
Grade 3 ◽  
Line Of Therapy

We evaluated outcomes of treatment with 5-fluorouracil (5-FU), doxorubicin, and streptozocin (FAS) in well-differentiated pancreatic neuroendocrine tumors (PanNETs) and its impact on subsequent therapy (everolimus or temozolomide). Advanced PanNET patients treated at our center from 1992 to 2013 were retrospectively reviewed. Patients received bolus 5-FU (400 mg/m2), streptozocin (400 mg/m2) (both IV, days 1-5) and doxorubicin (40 mg/m2 IV, day 1) every 28 days. Overall response rate (ORR) was assessed using RECIST version 1.1. Of 243 eligible patients, 220 were evaluable for ORR, progression-free survival (PFS), and toxicity. Most (90%) had metastatic, nonfunctional PanNETs; 14% had prior therapy. ORR to FAS was 41% (95% confidence interval [CI]: 36-48%). Median follow-up was 61 months. Median PFS was 20 (95% CI: 15-23) months; median overall survival (OS) was 63 (95% CI: 60-71) months. Cox regression analyses suggested improvement with first-line vs subsequent lines of FAS therapy. Main adverse events ≥ grade 3 were neutropenia (10%) and nausea/vomiting (5.5%). Dose reductions were required in 32% of patients. Post-FAS everolimus (n=108; 68% second line) had a median PFS of 10 (95% CI: 8-14) months. Post-FAS temozolomide (n=60; 53% > fourth line) had an ORR of 13% and median PFS of 5.2 (95% CI: 4-12) months. In this largest reported cohort of PanNETs treated with chemotherapy, FAS demonstrated activity without significant safety concerns. FAS did not appear to affect subsequent PFS with everolimus; this sequence is being evaluated prospectively. Responses were noted with subsequent temozolomide-based regimens although PFS was possibly limited by line of therapy.

Salvage immune checkpoint inhibitor (ICI) plus tyrosine kinase inhibitor (TKI) combination therapy for metastatic renal cell carcinoma (mRCC).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16567-e16567
Author(s):  
Anish B. Parikh ◽  
Sarah P. Psutka ◽  
Yuanquan Yang ◽  
Katharine Collier ◽  
Abdul Miah ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Immune Checkpoint Inhibitor ◽  
Kinase Inhibitor ◽  
Objective Response ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Free Survival ◽  
Kaplan Meier ◽  
Grade 3 ◽  
Combination Regimens

e16567 Background: ICI/TKI combinations are a new standard of care for the initial treatment (tx) of mRCC. Efficacy and toxicity of such combination regimens beyond the first-line (1L) setting remain unknown. Methods: We retrospectively reviewed charts for adult patients (pts) receiving an ICI/TKI combination in any line of tx for mRCC of any histology at one of two academic centers as of May 1, 2020. ICIs included pembrolizumab (Pm), nivolumab (Ni), ipilimumab (Ip), or avelumab (Av); TKIs included sunitinib (Su), axitinib (Ax), pazopanib (Pz), lenvatinib (Ln), or cabozantinib (Ca). Clinical data including pt demographics, histology, International mRCC Database Consortium (IMDC) risk group, tx history, and ICI/TKI tx and toxicity details were recorded. Outcomes included objective response rate (ORR), median progression-free survival (mPFS), and safety, analyzed via descriptive statistics and the Kaplan-Meier method. Results: Of 85 pts, 69 (81%) were male and 67 (79%) had clear cell histology. IMDC risk was favorable (24%), intermediate (54%), poor (20%), and unknown (2%). 39% had ICI/TKI tx in the 1L setting. ICI/TKI regimens included Pm/Ax (33%), Ni/Ca (25%), Ni/Ax (20%), Av/Ax (11%), Ni/Ip/Ca (8%), Ni/Su (2%), and Ni/Ln (1%). ORR and mPFS stratified by line of tx and prior tx are shown in the table. Of 52 pts who received ICI/TKI tx as salvage (after 1L), 52% had a grade 3 or higher (≥G3) adverse event (AE), of which the most common were anorexia (13.5%), diarrhea and hypertension (11.5% each), and fatigue (9.6%). 65% of pts on salvage ICI/TKI tx stopped tx for progression/death, while 16% stopped tx for ≥G3 AE. ≥G3 AE rates by line of tx were 62.5% (2L), 50% (3L), and 45% (≥4L). Conclusions: ICI/TKI combination therapy is effective and safe beyond the 1L setting. Prior tx history appears to impact efficacy but has less of an effect on safety/tolerability. These observations will need to be confirmed in prospective studies.[Table: see text]

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