Phase Ib trial of ALT-803, an IL-15 superagonist, plus Bacillus Calmette Guerin (BCG) for the treatment of patients with BCG-naïve non-muscle-invasive bladder cancer (NMIBC).

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 470-470 ◽  
Author(s):  
Charles Joel Rosser ◽  
Jeffrey Nix ◽  
Liza Hernandez ◽  
Peter R. Rhode ◽  
Hing C. Wong
Keyword(s):  
Clinical Trial ◽  
Response Assessment ◽  
Complete Response ◽  
Urinary Cytology ◽  
Induction Phase ◽  
Phase Ib ◽  
Risk Patients ◽  
Grade 3 ◽  
Muscle Invasive

470 Background: Novel agents are necessary to treat NMIBC to avoid recurrence and progression. This phase Ib clinical trial evaluated the safety and toleraibility of ALT-803, an IL-15 superagonist, plus BCG in patients with BCG-naïve NMIBC. Methods: This is a Phase Ib trial using the 3+3 design to evaluate intravesical ALT-803 plus BCG 50 mg in BCG-naïve NMIBC patients, who would normally be eligible for intravesical BCG alone. The initial dose of ALT-803 was 100 μg/instillation with 2 dose-escalations allowed (200 μg/instillation and 400 μg/instillation) if dose limiting toxicities (DLTs) were not evident. Patients received intravesical ALT-803 in conjunction with BCG weekly for 6 consecutive weeks (Induction Phase). Patients then had routine follow-up with cystoscopy and voided urinary cytology (VUC) every 3 months for 2 years equating to confirmatory response assessment. Negative cystoscopy, VUC and/or biopsy yielded a complete response (CR). When appropriate for high-risk patients, physicians and patients were encouraged to receive maintenance BCG alone as per common practice patterns. Results: No patient in 100 μg/instillation of ALT-803/BCG and 200 μg/instillation of ALT-803/BCG reported an AE. One patient in 400 μg/instillation/BCG cohort developed a urinary tract infection requiring delay of intravesical treatment by 1 week. No grade 3/4 toxicities were noted. All patients have completed therapy without DLTs. To date, 4 patients have 12 month follow-up and are CR. The remaining 5 patients have no evidence of disease. However, follow-ups are currently approximately 3 months. Corollary immune studies are still pending. Conclusions: Intravesical ALT-803 plus BCG was safe and tolerable in patients with BCG-naive NMIBC. Further evaluation in expansion cohorts in a phase II trial is currently underway. Clinical trial information: NCT02138734.

Keynote 057: Phase II trial of Pembrolizumab (pembro) for patients (pts) with high-risk (HR) nonmuscle invasive bladder cancer (NMIBC) unresponsive to bacillus calmette-guérin (BCG).

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 350-350 ◽  
Author(s):  
Arjun Vasant Balar ◽  
Girish S. Kulkarni ◽  
Edward M. Uchio ◽  
Joost Boormans ◽  
Loic Mourey ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Complete Response ◽  
Maculopapular Rash ◽  
Median Number ◽  
Kaplan Meier ◽  
Bcg Therapy ◽  
Duration Of Response ◽  
Grade 3 ◽  
Muscle Invasive

350 Background: The PD-1 inhibitor pembro has durable antitumor activity in pts with metastatic urothelial carcinoma. Upregulation of the PD-1 pathway has been observed in BCG-resistant NMIBC, suggesting pembro may benefit. Efficacy and safety of pembro in pts with HR, BCG-unresponsive NMIBC was evaluated in the single-arm phase 2 KEYNOTE-057 study; updated results for pts with carcinoma in situ (CIS) with or without papillary tumor (cohort A) are reported. Methods: Pts with histologically confirmed HR, BCG-unresponsive CIS with or without papillary disease, who received adequate BCG therapy and were unable/unwilling to undergo radical cystectomy received pembro 200 mg Q3W for 24 mo or until recurrence, progression, or unacceptable toxicity. Pts with HR NMIBC or progressive disease during treatment were required to discontinue. Primary end point: complete response rate (CRR); key secondary end points: duration of response and safety. Results: 103 pts (median age 73 years; CIS alone 71.8%; median number of prior BCG instillations 12) have enrolled in cohort A. 3-mo CRR rate was 38.8% (95% CI 29.4%-48.9%) by central assessment. Among 40 pts who achieved CR at 3 mo, 72.5% maintained CR at last follow-up (median 14.0 mo; range 4.0-26.3) and median CR duration has not been reached (range 0+ to 14.1+ mo). 80.2% of pts had a CR duration of ≥6 mo (Kaplan-Meier method). 10 (25.0%) experienced recurrent NMIBC after CR; at the time of analysis, none progressed to muscle invasive or metastatic disease. Treatment-related adverse events (AEs) occurred in 65 (63.1%) pts; most frequent were pruritus (10.7%), fatigue (9.7%), diarrhea (8.7%), hypothyroidism (5.8%), and maculopapular rash (5.8%). Grade 3/4 treatment-related AEs occurred in 13 (12.6%) pts; 1 death was considered treatment-related (colitis in patient inadequately treated with steroids). Immune-mediated AEs occurred in 19 (18.4%) pts. Conclusions: Pembro had encouraging activity in pts with HR, BCG-unresponsive CIS with or without papillary tumors and a safety profile consistent with that of previous experience. Updated data using additional follow-up will be presented. Clinical trial. Clinical trial information: NCT02625961.

Phase I trial of ALT-801, a first-in-class T-cell receptor (TCR)-interleukin (IL)-2 fusion molecule, plus gemcitabine (G) for Bacillus Calmette Guerin (BCG)-resistant non-muscle-invasive bladder cancer (NMIBC).

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 451-451 ◽  
Author(s):  
Guru Sonpavde ◽  
Charles Joel Rosser ◽  
Chong-xian Pan ◽  
Rahul Atul Parikh ◽  
Jeffrey Nix ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Phase I ◽  
Phase I Trial ◽  
Response Assessment ◽  
Complete Response ◽  
Cell Receptor ◽  
Clinical Activity ◽  
Maintenance Cycle ◽  
Step Down ◽  
Grade 3

451 Background: Novel agents are necessary to treat BCG-resistant NMIBC to avoid radical cystectomy (RC). This phase I clinical trial evaluated the safety and activity of ALT-801, a recombinant humanized TCR-IL-2 fusion protein in BCG-resistant NMIBC. Methods: This is a Phase I trial using the 3+3 design to evaluate intravenous (IV) ALT-801 plus IV G 1000 mg/m2 in BCG-resistant high-risk NMIBC patients (pts) defined as high grade Ta, T1 or carcinoma in situ, size > 4 cm or multi-focal tumors. BCG-intolerant pts, those who refused or were unfit to undergo RC were also eligible. Initially, patients received ALT-801 monotherapy; an amendment added G. Pts received induction of 2 cycles, with a 13-day rest between cycles. Each cycle consisted of 4 doses of ALT-801 on Day 3, Day 5, Day 8, and Day 15 and 2 doses of G, one each on Day 1 and Day 8. Pts who have a biopsy-proven complete response (CR) after induction received one maintenance cycle and underwent response assessment. The initial dose of ALT-801 was 0.08 mg/kg with 2 step-down doses allowed if dose limiting toxicities (DLTs)- 0.06 mg/kg and 0.04 mg/kg. Results: 2 pts in cohort one received ALT-801 alone at 0.08 mg/kg per dose, a 3rd pt received G and ALT-801 at 0.08 mg/kg per dose. Grade ≥ 3 hepatotoxicity in the 3rd patient led to a step-down to 0.06 mg/kg dose. One pt in the 0.06 mg/kg dose experienced a DLT (Grade ≥ 3 hepatotoxicity) and the cohort was expanded to 6 pts with no further DLTs. Other attributed adverse events were: anorexia, pruritus, rash, edema, fatigue, chills. For the 0.06 mg/kg ALT-801 + G regimen, 6 pts received up to 2 cycles of induction and 4 pts received the maintenance cycle. All pts have completed therapy without further DLTs. CR was observed in 3 pts, which was durable in 2 pts lasting ≥ 18 months. Preliminarily immune studies have shown transient IFN-γ and IL-6 but not TNF-α and IL-10 induction after ALT-801 dosing. Conclusions: ALT-801 plus gemcitabine was feasible in BCG-resistant NMIBC and demonstrated immune responses and potential durable clinical activity. Further evaluation in expansion cohorts in a phase Ib/II trial is planned. Clinical trial information: NCT01625260.

Phase Ib trial of ALT-803, an IL-15 superagonist, plus BCG for the treatment of BCG-naïve patients with non-muscle-invasive bladder cancer.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 510-510 ◽  
Author(s):  
Charles Joel Rosser ◽  
Jeffrey Nix ◽  
Lydia Ferguson ◽  
Liza Hernandez ◽  
Hing C. Wong
Keyword(s):  
Clinical Trial ◽  
High Risk ◽  
Standard Of Care ◽  
Complete Response ◽  
Disease Recurrence ◽  
Urinary Cytology ◽  
Current Standard ◽  
Phase Ib ◽  
Standard Practices ◽  
Disease Free

510 Background: The current standard of care for patients with high risk NMIBC is a TURBT or biopsy followed by a 6-week induction course of intravesical BCG and supplementary maintenance therapies every 3 months thereafter (Lamm 2000). While clinical response is significantly improved with BCG, 50% of patients are still expected to recur within 12 months ( Sfakianos 2014). The pursuit of novel agents to prevent progression and recurrence of NMIBC remains critical. This phase Ib clinical trial evaluates the safety and tolerability of ALT-803, an IL-15 superagonist, plus BCG in BCG-naïve NMIBC patients. Methods: A dose escalation 3+3 design was employed to evaluate intravesical ALT-803 plus 50 mg BCG in BCG-naïve patients with intermediate or high-risk Ta, T1 or Tis stage NMIBC. Patients received intravesical ALT-803 in conjunction with BCG weekly for 6 consecutive weeks (induction) and then encouraged (but not required) to receive maintenance BCG alone as per standard practices. Patients had a routine cystoscopy and voided urinary cytology (VUC) every 3 months for 2 years to determine response. Negative cystoscopy, VUC and/or biopsy yielded a complete response (CR). No cohort (100, 200 or 400 μg/instillation ALT-803) experienced any dose limiting toxicities. Results: All patients are disease-free (CR) at 24 months; no patients experienced disease recurrence or progression. Adverse events consistent with SoC BCG treatment (hematuria and urinary tract pain) were reported in all cohorts. One patient experienced a grade 3 adverse event of hypertension that resolved the same day. No grade 4 toxicities or DLTs were observed. Clinical trial information: NCT02138734. Conclusions: Intravesical ALT-803 plus BCG treatment is well tolerated in BCG-naïve patients with NMIBC. All patients are disease-free 24 months after treatment with BCG and ALT-803. A randomized phase II trial is currently underway.[Table: see text]

A pilot presurgical study evaluating anti-PD-L1 durvalumab (durva) plus anti-CTLA-4 tremelimumab (treme) in patients (pts) with high-risk muscle-invasive bladder carcinoma (MIBC) who are ineligible for cisplatin-based neoadjuvant chemotherapy (NAC).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 4551-4551 ◽  
Author(s):  
Jianjun Gao ◽  
Arlene O. Siefker-Radtke ◽  
Neema Navai ◽  
Matthew T Campbell ◽  
Rebecca Slack Tidwell ◽  
...  
Keyword(s):  
Clinical Trial ◽  
High Risk ◽  
Neoadjuvant Therapy ◽  
Complete Response ◽  
Surgical Trial ◽  
Variant Histology ◽  
Grade 3 ◽  
Muscle Invasive ◽  
Immunosuppressive Microenvironment ◽  
Surgery Delay

4551 Background: In MIBC pts, especially in those with high risk features including lymphovascular invasion, hydronephrosis, T3b disease, or variant histology, cisplatin-based NAC followed by cystectomy improves overall survival as compared with cystectomy alone. However, it is estimated that over 50% of pts with MIBC are ineligible for cisplatin-containing therapy. Therefore, we propose this pre-surgical trial with durva + treme for this population of pts. Methods: This is a single-arm, pre-surgical clinical trial with durva + treme in pts with localized, high-risk MIBC (cT2-T4a) who are ineligible for cisplatin-based NAC due to decreased renal function, neuropathy, hearing loss, or heart failure; or refuse cisplatin-based NAC (NCT02812420). Each patient receives durva (1500 mg) plus treme (75 mg) on weeks 1 and 5. Pts then undergo surgery at week 9-11. Pre- and post-treatment blood and tumor samples are collected for correlative biological analyses. Results: Twenty eight of 35 pts have been enrolled on this trial. Twenty-one pts have completed cystectomy as of 11/16/19. Of these 21 pts, 9 (43%) had pathologically complete response (pCR) and two (10%) had pathologic T1N0 (pT1) disease (≤pT1N0 rate = 52%). Fourteen of 21 (67%) had down-staging of disease. Of note, 10 of these 21 pts had 3-D mass (T3) on exam under anesthesia or clinical T4a disease; 5 of these 10 pts (50%) had pCR and one (10%) had pT1 disease (≤pT1N0 rate = 60%). Only 5 of 28 (17%) pts developed grade 3 immune related toxicity including hepatitis and amylase/lipase elevation, and two (7%) resulted in surgery delay for > 30 days. Immune profiling with CyTOF analysis of baseline peripheral blood indicates that pts with pCR have significantly lower frequency of a Th2 subset as compared to pts with up-staging of disease. In addition, gene expression profiling analysis of baseline tumor tissues demonstrates a significantly less immunosuppressive microenvironment in pts with pCR as compared to pts with up-staging of disease. Conclusions: Our data indicate that durva plus treme is an effective and safe neoadjuvant therapy for pts with MIBC ineligible for cisplatin-based therapy. Therefore, neoadjuvant therapy with durva + treme and a number of potential biomarkers warrant testing in a larger phase 3 trial. Clinical trial information: NCT 02812420.

Pembrolizumab (pembro) for patients (pts) with high-risk (HR) non–muscle invasive bladder cancer (NMIBC) unresponsive to Bacillus Calmette-Guérin (BCG): Updated follow-up from KEYNOTE-057.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 4530-4530 ◽  
Author(s):  
Ronald De Wit ◽  
Girish S. Kulkarni ◽  
Edward M. Uchio ◽  
Laurence Eliot Miles Krieger ◽  
Joost L. Boormans ◽  
...  
Keyword(s):  
Complete Response ◽  
Median Number ◽  
Kaplan Meier ◽  
Immune Mediated ◽  
Bcg Therapy ◽  
Duration Of Response ◽  
Grade 3 ◽  
Muscle Invasive

4530 Background: Upregulation of the PD-1 pathway has been observed in BCG-unresponsive NMIBC, suggesting that pembro may be beneficial. Efficacy and safety of pembro in pts with HR, BCG-unresponsive NMIBC was evaluated in the single-arm phase 2 KEYNOTE-057 study (NCT02625961); updated results for pts with carcinoma in situ (CIS) with or without papillary tumors (cohort A) are reported. Methods: Pts with histologically confirmed HR, BCG-unresponsive CIS with or without papillary tumors who received adequate BCG therapy and were unable/refused to undergo radical cystectomy received pembro 200 mg Q3W for 24 mo or until recurrence, progression, or unacceptable toxicity. Pts who developed HR NMIBC or progressive disease during treatment were required to discontinue. Key end points were complete response rate (CRR), duration of response, and safety. Results: 102 pts (median age, 73 years; CIS alone, 63.7%; median number of prior BCG instillations, 12) had enrolled in cohort A as of enrollment cutoff. Median (range) duration of follow-up was 15.8 mo (4.6-28.2) ; 3-mo CRR was 40.2% (95% CI, 30.6-50.4) by central assessment. Among 41 pts who had CR at 3 mo, median CR duration was 12.7 mo (range, 0+ to 20.5+ mo); 75.4% had a CR duration ≥ 6 mo; 52.6% had a CR duration ≥12 mo (Kaplan-Meier method); 24 pts (58.5%) maintained CR at last follow-up, and 15 (36.6%) experienced recurrent NMIBC after CR; at the time of analysis, none progressed to muscle-invasive or metastatic disease. CRR was 44.6% for pts with CIS alone (n = 65), 41.7% for CIS with T1 tumors (n = 12), and 28.0% for CIS with high-grade Ta tumors (n = 25). Treatment-related adverse events (AEs) occurred in 66 (64.7%) pts; most frequent (≥10%) were pruritus (10.8%), diarrhea (10.8%), and fatigue (9.8%). Grade 3/4 treatment-related AEs occurred in 13 (12.7%) pts. Immune-mediated AEs occurred in 19 (18.6%) pts. Conclusions: Pembro continued to show encouraging antitumor activity in pts with HR, BCG-unresponsive CIS with or without papillary tumors and a safety profile consistent with that of previous experience. Updated data using additional follow-up will be presented. Clinical trial information: NCT02625961.

Pembrolizumab (pembro) for the treatment of patients with Bacillus Calmette-Guérin (BCG) unresponsive, high-risk (HR) non–muscle-invasive bladder cancer (NMIBC): Over two years follow-up of KEYNOTE-057.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 5041-5041 ◽  
Author(s):  
Arjun Vasant Balar ◽  
Ashish M. Kamat ◽  
Girish S. Kulkarni ◽  
Edward M. Uchio ◽  
Joost L. Boormans ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Complete Response ◽  
Disease Recurrence ◽  
Intravesical Therapy ◽  
Efficacy Analysis ◽  
Bcg Therapy ◽  
Duration Of Response ◽  
Grade 3 ◽  
Muscle Invasive

5041 Background: Pembro was recently approved for the treatment of HR NMIBC based on results from the phase 2 KEYNOTE-057 (NCT02625961) study. Herein we present safety, efficacy, and posttreatment outcomes with > 2 y follow-up from KEYNOTE-057 cohort A. Methods: Patients with histologically confirmed HR BCG-unresponsive carcinoma in situ (CIS) with or without papillary tumors who received adequate BCG therapy and were ineligible for or opted out of radical cystectomy (RC) received pembro 200 mg Q3W for up to 2 y or until disease recurrence, progression, or unacceptable toxicity. The primary end point was complete response rate (CRR). Key secondary end points were duration of response (DOR) and safety. Results: Overall, 102 patients were initially enrolled, and 96 were included in the efficacy analysis. Median time from enrollment to data cut off was 28.4 months (range, 18.2-40.5). CRR was 40.6% (95% CI, 30.7-51.1), and median DOR was 16.2 months (range, 0+ to 30.4+). Among 39 patients with CR, 18 (46.2%) had a DOR ≥12 months. No patient’s disease progressed to muscle-invasive or metastatic bladder cancer while on study treatment. Median PFS and OS were not reached. At 12 months, PFS was 82.7% and OS was 97.9%. A total of 36 patients (37.5%) underwent RC after discontinuation from study treatment, which included 9 of 22 patients (40.9%) who had recurrence after initial CR and 27 of 57 (47.4%) nonresponders. Of the 36 who underwent RC, 33 (91.6%) had no pathological upstaging to MIBC and 3 (8.3%) had at least pT2 disease at time of RC. For subsequent treatments other than RC, 27 of 96 (28.1%) patients received additional intravesical therapy (eg, BCG, gemcitabine, or mitomycin), 21 of 96 (21.9%) underwent local procedures (eg, TURBT), and 3 of 96 (3.1%) received systemic therapy (eg, pembro). In 102 patients treated with pembro, treatment-related AEs (TRAEs) occurred in 67 (65.7%) patients; most frequently reported TRAEs were fatigue, pruritus, and diarrhea (10.8% each). Grade 3/4 TRAEs occurred in 13 patients (12.7%), and 21 patients (20.6%) experienced immune-mediated AEs. There were no grade 5 TRAEs. Conclusions: After > 2 y of follow-up, durable and clinically meaningful activity of pembro was observed in patients who had HR BCG-unresponsive CIS with or without papillary tumors and who were ineligible for or opted out of RC. Pembro did not seem to limit the opportunity for subsequent therapies, including RC. The safety profile was consistent with what is reported in the literature. Clinical trial information: NCT02625961 .

Feasibility study of TAS-118 plus oxaliplatin as perioperative chemotherapy for patients with locally advanced gastric cancer (APOLLO-11).

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 205-205
Author(s):  
Daisuke Takahari ◽  
Manabu Ohashi ◽  
Atsuo Takashima ◽  
Takuro Mizukami ◽  
Naoki Ishizuka ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Advanced Gastric Cancer ◽  
Locally Advanced ◽  
Dose Intensity ◽  
Complete Response ◽  
Free Survival ◽  
D2 Gastrectomy ◽  
Locally Advanced Gastric Cancer ◽  
Grade 3

205 Background:TAS-118 (S-1 and leucovorin) + oxaliplatin (L-OHP) improved overall survival (OS) compared to S-1 + cisplatin for patients (pts) with advanced gastric cancer (GC) (Kang, Lancet Oncol. 2020). This study investigated the feasibility of peri (pre and post)-operative (op) chemotherapy (chemo) with TAS-118 ± L-OHP in pts with locally advanced resectable GC. While it was reported that pre-op TAS-118 + L-OHP followed by D2 gastrectomy was well tolerated and showed promising efficay (Takahari, ASCO-GI. 2020), the recommended post-op chemo regimen, TAS-118 or TAS-118 + L-OHP, has yet to be determined. Methods:Eligible pts with GC of clinical T3-4N1-3M0 were enrolled. The protocol treatment consisted of pre-op chemo with 4 courses of TAS-118 (40-60 mg/body, orally, twice daily, 7 days) + L-OHP (85 mg/m2, intravenously, day 1) in a 2-week cycle, and gastrectomy with D2 lymphadenectomy, followed by post-op chemo with 12 courses of TAS-118 (step 1) and 8 courses of TAS-118 + L-OHP (step 2). Step 2 was started if the dose-limiting toxicity (DLT) occurred in < 6 of 10 pts in step 1. Up to 20 pts were included in the analysis of feasibility after a recommended regimen was determined. Results:Between December 2016 and February 2019, 45 pts were enrolled. The numbers of pts with cT3/4a and cN1/2/3 were 13/32 and 25/17/3, respectively. Excluding 14 pts (4 achieving pathological complete response, 4 not satisfying the criteria for post-op chemo, 3 physician judgement or pt withdrawal, 2 progressive disease, 1 adverse event [AE]), 31 pts (11/20 in step 1/2) received the post-op chemo. No DLT was observed in either step. The post-op chemo completion rate was 90.9% (95% CI, 63.6-99.5) in step 1 and 80.0% (95% CI, 59.9-92.9) in step 2. The median relative dose intensity of TAS-118 in step 1 was 83.3%, and those of TAS-118 and L-OHP in step 2 were 69.9% and 74.3%, respectively. One pt in step 2 discontinued post-op chemo due to AE. Grade ³ 3 AEs observed in ≥ 10% of pts were weight loss in both step 1 and step 2 (2 in each), and hypokalemia (n = 3) and neutropenia (n = 2) in step 2. At 1-year follow-up after the last pt was enrolled, recurrence-free survival and OS rates were 91.1% (95% CI, 78.0-96.6) and 100%, respectively at 12 months, and 69.1% (95% CI, 49.6-82.3) and 95.5% (95% CI, 71.9-99.3), respectively at 24 months. Conclusions:Taken together with the feasibility and efficacy of pre-op chemo, peri-op chemo with TAS-118 + L-OHP with D2 gastrectomy was well tolerated and showed promising efficacy. Clinical trial information: UMIN000024688.

scholarly journals Efficacy and safety of daratumumab in the treatment of multiple myeloma: a systematic review and meta-analysis

2021 ◽  
Vol 49 (8) ◽  
pp. 030006052110381
Author(s):  
Yin Wang ◽  
Yanqing Li ◽  
Ye Chai
Keyword(s):  
Multiple Myeloma ◽  
Meta Analysis ◽  
Complete Response ◽  
Library Science ◽  
Cochrane Library ◽  
Control Group ◽  
Efficacy And Safety ◽  
Risk Patients ◽  
Grade 3 ◽  
Combination Regimens

Objective To systematically evaluate the efficacy and safety of combination regimens containing daratumumab in patients with multiple myeloma (MM). Methods A systematic search of publications listed on electronic databases (PubMed®, The Cochrane Library, Science Direct and Web of Science) between inception and 13 November 2020 was conducted to find randomized controlled trials (RCTs) that included patients with MM that were treated with combination regimens containing daratumumab. Results A total of seven RCTs were included ( n = 4268 patients). Meta-analysis showed that compared with the control group, the group containing daratumumab showed a significantly better overall response rate and a complete response or better. Daratumumab improved efficacy in both standard-risk and cytogenetically high-risk patients with MM. The prevalence of neutropenia (≥grade 3) and pneumonia was significantly higher in the daratumumab group compared with the control group. Conclusion The available evidence demonstrated that the clinical application of combination regimens containing daratumumab improved the efficacy in patients with MM and had acceptable safety.

scholarly journals IDH2 Inhibitor Therapy in Relapsed and Refractory Acute Myeloid Leukemia: A Single Institution Experience

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 43-44
Author(s):  
Marissa Li ◽  
Erika Morsia ◽  
Christopher E. Wee ◽  
Kristen McCullough ◽  
Aref Al-Kali ◽  
...  
Keyword(s):  
Myeloid Leukemia ◽  
Platelet Transfusion ◽  
Median Overall Survival ◽  
Response Assessment ◽  
Complete Response ◽  
Transfusion Independence ◽  
Transfusion Dependency ◽  
Initiation Of Therapy ◽  
Acute Myeloid

Introduction: Mutations in the gene isocitrate dehydrogenase 2 (IDH2) occur in ~12-15% of patients with acute myeloid leukemia (AML). Enasidenib, an oral small molecule selective targeted inhibitor of IDH2 enzymes, was approved forIDH2mutated relapsed/refractory AML (RR-AML) in 2017 (Stein et. al., 2017). There is limited data regarding its efficacy and toxicity outside the context of clinical trials. Using Mayo Clinic's cohort of AML patients, we provide a real-world look at outcomes forIDH2mutated RR-AML patients treated with enasidenib. Methods: A total of 13 patients treated with enasidenib for RR-AML were identified, all of which experienced at least one relapse following induction chemotherapy. Response assessment was based on European Leukemia Net (ELN) 2017 response criteria.Complete blood counts including blast percentage and transfusion dependency were obtained at AML diagnosis, initiation of enasidenib, 2 months and 6 months following initiation of therapy. Transfusion dependency was defined by the need for either a red cell or platelet transfusion within 4 weeks of the designated time frame. We compared the clinical characteristics of patients who achieved complete response (CR) (n=4) to those not achieving CR (n=9), using the Mann-Whitney U test for numerical variables and the Fischer's Exact test for quantitative data. Results: The median age at diagnosis of our 13 patients was 68 years (range 60-82), with a male predilection (n=11) (Table 1). Cytogenetic and molecular genetic findings are provided in Table 2. Complete response (CR) was achieved in 4 (30.7%) patients by cycle 2 and 2 of those patients (50%) proceeded to an allogeneic hematopoietic stem cell transplant (AHSCT). The median time from diagnosis to initiation of treatment for patients in CR was 3.5 months (range 1-7), and for patients not achieving CR was 13 months (range 6-53; p=0.048), with median time of follow up after treatment initiation of 23.5 months (range, 5-36) and 7 months (range, 1-14), respectively. Among 8 patients who were transfusion dependent at baseline, all the CR patients (2/2) achieved red blood cell and platelet transfusion independence 6 months after treatment, instead only (3/6) 50% of those not in CR achieved transfusion independence (p=0.028). An initial trajectory of improvement in counts is noted from the time of diagnosis to the 2 month mark post treatment with 75% of the responder cohort showing improvement in counts which was durable through the 6 month mark, whereas 55% of those that did not respond had worsening counts at month 2 and died prior to 6 month follow up. At the time of data cut-off, the median duration of CR was 14 months (range, 2-33), with 3 of 4 (75%) of responders maintaining CR. Figure 1 details overall responses and outcomes in all 13 patients. None of the patients in our study experienced differentiation syndrome. Five patients were hospitalized in the course of treatment for infectious complications. Two patients were noted to have hyperbilirubinemia however there was no clear indication that this was secondary to enasidenib Median overall survival for all 13 patients was 21 months (range, 6-53 months) with leukemia free survival of 7 months (range, 5-19 months). Furthermore, median overall survival for patients in CR was 27 months (range, 6-42), and those not in CR was 16 months (range, 6-53) (p=0.20). In addition, we observed that 75% of patients who attained CR are alive compared to 11.1% of those not in CR (p = 0.052). Conclusion: We demonstrate a superior CR rate of 30.7% with enasidenib amongstIDH2mutated RR-AML patients compared with clinical trial data showing CR rate of 19.6% (Stein et. al., 2019) despite our patients being heavily pre-treated with median number of two prior therapies (range; 1-5) including prior AHSCT in 2 patients. Moreover, a subset of patients (2 of 4 in CR) were able to undergo ASCHT. Finally, the achievement of CR at 2 months after initiation of therapy serves as an appropriate time point for response assessment. Disclosures No relevant conflicts of interest to declare.

A phase III multicenter randomized clinical trial to compare cisplatin plus fluorouracil with or without docetaxel as the first-line induction chemotherapy for locoregionally advanced nasopharyngeal carcinoma: Long-term outcomes update.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 6032-6032
Author(s):  
Wang Fang FangZheng
Keyword(s):  
Clinical Trial ◽  
Nasopharyngeal Carcinoma ◽  
Induction Chemotherapy ◽  
Phase Iii ◽  
Karnofsky Performance Score ◽  
Long Term Outcomes ◽  
First Line ◽  
Grade 3

6032 Background: A phase III multicenter prospective randomized controlled trial was conducted to compare cisplatin plus 5-fluorourcil with or without docetaxel as first-line induction chemotherapy in the patients with locoregionally advanced nasopharyngeal carcinoma (LANPC). Here, we report on the long-term outcomes and late toxicities of the trial (NCT01536223). Methods: Patients with newly diagnosed LANPC, stage III-IV disease, Karnofsky performance score≥70, without metastasis were eligible and randomly assigned 1:1 to TPF versus PF for three cycles. The primary end point was progression-free survival; local control, OS and advent events were important key secondary end points. The Kaplan-Meier method and the log-rank test were used to conduct and compare the survival curves in this study. Results: Two hundred ninety-nine patients were enrolled. 276 patients (138 TPF and 138 PF) were evaluable. Baseline characteristics were well-balanced between two groups, and the median age was 48 (range, 18-60 years). The ORR rates after induction chemotherapy and chemoradiotherapy were 90.6% and 9797.8% in TPF group and 87.0% (P > 0.05) and 97.8% (P > 0.05), respectively. The median follow-up was 99 months. For all patients, the 5- and 8-year OS and PFS were 76.9% and 74.9%, 72.3% and 69.1%, respectively. PF was associated with a similar PFS versus TPF ( 5-year PFS of 72.4% versus 73.2%, P =.747), and an equivalent OS at 5 years ( 79.2% and 79.1%, P = 0.519). Treatment-related grade 3 to 4 advent events were less frequent with PF compared with TPF. Conclusions: With prolonged follow-up, the survival outcomes in the PF group were not non-inferiority to those in the TPF group, but grade 3 to 4 advent events were less frequent. Clinical trial information: NCT01536223.

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