Combination immunotherapy with ipilimumab and nivolumab in patients with rare gynaecological malignancies.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 6091-6091
Author(s):  
Oliver Klein ◽  
Damien Kee ◽  
Bo Gao ◽  
Ben Markman ◽  
Linda R. Mileshkin ◽  
...  
Keyword(s):  
Clear Cell ◽  
Single Agent ◽  
Low Grade ◽  
Gynecological Cancers ◽  
Prior Therapy ◽  
Gynecological Malignancies ◽  
Duration Of Response ◽  
Radiological Response ◽  
Grade 3 ◽  
Tumor Types

6091 Background: Up to 50% of gynecological cancers are considered rare. The outcome of these patients (pts) is poor given a lack of scientific and clinical knowledge. Immunotherapy using single agent anti- PD-1/PD-L1 treatment (tx) has shown only modest activity in patients with common gynecological malignancies, such as high grade serous ovarian cancer (ca) and microsatellite stable endometrial ca. Combined CTLA-4/PD-1 blockade using ipilimumab (ipi) and nivolumab (nivo) has demonstrated superior efficacy compared to single agent anti-PD-1 therapy in pts with advanced melanoma and renal cell ca. To date, no trials have been undertaken with ipi/nivo in patients with rare gynecological malignancies. Methods: 41 pts with advanced rare gynecological malignancies were enrolled into the CA209-538 trial. Pts received nivo 3mg/kg and ipi 1mg/kg q 3 weekly for four doses, followed by nivo 3mg/kg q 2 weekly. Tx continued for up to 96 weeks, or until disease progression or the development of unacceptable toxicity. Response (RECIST 1.1) was assessed every 12 weeks. The primary endpoint was clinical benefit rate (CBR = CR +PR + SD). Exploratory endpoints include correlation of efficacy with biomarkers (incl PD-L1/TMB). Results: Pts with 10 rare tumor types were enrolled (Table). 39/41 pts have received prior therapy (1-7 lines). Objective responses were observed in 11 pts (27%) including pts with vaginal SCC, ovarian clear cell and low grade serous ca, ovarian and uterine carcinosarcoma, uterine clear cell, uterine serous ca and leiomyosarcoma. A further 9 pts had SD as their best radiological response resulting in a CBR of 49%. The median duration of response had not been reached (range 3.5 – 25+ months) with seven responses being ongoing. 63% of pts experienced an immune related adverse event (irAEs) with 4 pts developing Grade 3/4 irAEs. Conclusions: Ipi/Nivo tx demonstrates efficacy in a range of different rare gynecological cancers with a significant number of durable responses being observed. Tumor agnostic biomarkers are required to assist with better patient selection. Clinical trial information: NCT02923934. [Table: see text]

Inducible T-cell co-stimulatory (ICOS) receptor agonist, feladilimab (fela), alone and in combination (combo) with pembrolizumab (P): Results from INDUCE-1 urothelial carcinoma (UC) expansion cohorts (ECs).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4519-4519
Author(s):  
Arjun Vasant Balar ◽  
Victor Moreno ◽  
Eric Angevin ◽  
Hui Kong Gan ◽  
Maria Vieito ◽  
...  
Keyword(s):  
T Cell ◽  
Single Agent ◽  
Clinical Activity ◽  
Prior Therapy ◽  
Metastatic Setting ◽  
Duration Of Response ◽  
Prior Systemic Therapy ◽  
Grade 3 ◽  
Tumor Types

4519 Background: INDUCE-1 is a first-in-human trial evaluating fela, an IgG4 ICOS agonist non-T-cell depleting mAb, as monotherapy (mono) and in combo with P. ECs include tumor types, such as UC, with high ICOS expression and immunotherapy-favorable features. Fela induced IFNγ, increased PD-1/L1 expression, and enhanced antitumor activity in combo with PD-1 blockade nonclinically. We report preliminary efficacy, safety, and biomarker data of fela ± P in INDUCE-1 UC ECs. Methods: Eligible patients (pts) had recurrent/metastatic (R/M) UC of the upper or lower urinary tract, ≤6 prior systemic therapy lines in the advanced setting, measurable disease, and no active autoimmune disease. Pts received 0.3 or 1 mg/kg fela (mono EC; anti-PD-1/L1–experienced [exp] pts) or 0.3 mg/kg fela + 200 mg P (combo EC; anti-PD-1/L1–naïve pts) every 3 wks, up to 35 cycles until disease progression or unacceptable toxicity. Disease was assessed every 9 wks through wk 54, then every 12 wks. Archival and/or fresh biopsy tumor tissue was collected for biomarker analyses and safety assessed. Results: By Nov 6 2020, 13 anti-PD-1/L1–exp and 32 anti-PD-1/L1–naïve pts were evaluable in the mono and combo ECs, respectively. In the mono EC, median age was 69 yrs (range: 47–82), 92% of pts were male, and 85% received ≥2 prior therapy lines in the metastatic setting. In the combo EC, median age was 70 yrs (range: 42–84), 75% of pts were male, and 72% received ≥1 prior therapy line in the metastatic setting. In the mono EC, median duration of follow-up (mDoF) was 10.6 mo (range: 1.1–22.8); overall response rate (ORR) was 8% (1 partial response [PR]; 95% CI: 0.2, 36.0) with a duration of response (DoR) of 6.1 mo; disease control rate (DCR [response or stable disease for ≥9 wks]) was 23% (95% CI: 5.0, 53.8), and median overall survival (mOS) was 14.5 mo (95% CI: 2.8, NR), with 74% of pts alive at 6 mo. In the combo EC, mDoF was 9.6 mo (range: 0.9–28.3); ORR was 22% (7 PRs; 95% CI: 9.3, 40.0) with a median DoR of 8.3 months (range: 3.5–23.3+); DCR was 63% (95% CI: 43.7, 78.9), and mOS was 10.7 mo (95% CI: 5.2, 18.1), with 64% of pts alive at 6 mo. Grade ≥3 treatment-related AEs were reported for 0% and 9% of pts in the mono (N = 16) and combo (N = 44) safety populations, respectively. PD-L1 expression and ICOS-specific biomarkers are being evaluated, with promising trends observed in enrichment of clinical activity in preliminary analyses. Conclusions: Fela is the first ICOS agonist with reported single-agent activity in anti-PD-1/L1–exp relapsed/refractory UC. Fela + P in combo shows promising clinical activity and manageable safety in PD-1/L1–naïve R/M UC. Further study is warranted. Updated data to be presented. Funding: Study 204691 (NCT02723955) funded by GlaxoSmithKline in collaboration with Merck Sharp & Dohme Corp, a subsidiary of Merck & Co, Inc, Kenilworth, NJ, USA. Clinical trial information: NCT02723955.

Durable Responses with Bortezomib in Patients with Relapsed or Refractory Mantle Cell Lymphoma (MCL): Updated Time-to-Event Analyses of the Multicenter PINNACLE Study.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 125-125 ◽  
Author(s):  
Andre Goy ◽  
Steven Bernstein ◽  
Brad Kahl ◽  
Benjamin Djulbegovic ◽  
Michael Robertson ◽  
...  
Keyword(s):  
Peripheral Neuropathy ◽  
Median Time ◽  
International Workshop ◽  
Single Agent ◽  
Stage Iv ◽  
Time To Event ◽  
Prior Therapy ◽  
Duration Of Response ◽  
Grade 3

Abstract Background: We previously reported substantial activity with single-agent bortezomib (VELCADE®; Vc) in patients (pts) with relapsed or refractory MCL in the PINNACLE study (JCO2006;24:4867–74), which resulted in approval of Vc for MCL pts following ≥1 prior therapy. All pts have now completed treatment. Here we report updated time-to-event data in all pts, and by response category, with extended follow-up. Methods: 155 pts (median age 65 yrs; 55%/41%/4% with 1/2/≥3 prior therapies; 77% Stage IV MCL; 55% positive bone marrow) received Vc 1.3 mg/m2 on days 1, 4, 8, and 11 of 21-day cycles; of these, 141 were response-evaluable. Response and progression were determined by modified International Workshop Response Criteria using independent radiology review. Results: After a median follow-up of 26.4 mo, 55 pts (35%) remained in follow-up; 93 (60%) had died, 2 (1%) had withdrawn consent, and 5 (3%) were lost to follow-up. Pts received a median of 4 treatment cycles (range 1–21; 8 in responding pts). Median time to first response was 1.3 months. Median duration of response (DOR) was 9.2 mo in all responders and has not been reached in pts achieving CR/CRu. Median time to progression (TTP), time to next therapy (TTNT; first Vc dose to start of next therapy), and overall survival (OS) are shown in the table for all pts and by response. Survival rate at 12-mo was 69% overall and 91% in responding pts. In pts refractory to their last therapy (no response or response with TTP <6 mo; n=58), median DOR was 5.9 mo, median TTP was 3.9 mo, median TTNT was 4.6 mo, and median survival was 17.3 mo. Safety profile was similar to previously reported; most common grade ≥3 AEs were peripheral neuropathy (13%), fatigue (12%), and thrombocytopenia (11%). The most common AE resulting in Vc discontinuation was peripheral neuropathy (10%). Twelve (8%) pts died on-study, including 5 (3%) considered related to Vc. Conclusions: Vc provides durable responses plus prolonged time off-therapy and survival in responding pts, suggesting substantial clinical benefit in relapsed/refractory MCL. Median TTP, TTNT, and OS (months) in all pts and by response All pts (N=155) Responders (N=45) CR/CRu (N=11) PR (N=34) SD (N=52) PD (N=34) NE, not estimable TTP 6.7 12.4 NE 9.1 6.9 1.2 TTNT 7.4 14.3 23.9 13.3 7.0 2.3 OS 23.5 35.4 36.0 35.1 27.8 13.7

Phase II study of daratumumab (DARA) monotherapy in patients with ≥ 3 lines of prior therapy or double refractory multiple myeloma (MM): 54767414MMY2002 (Sirius).

2015 ◽  
Vol 33 (18_suppl) ◽  
pp. LBA8512-LBA8512 ◽  
Author(s):  
Sagar Lonial ◽  
Brendan M. Weiss ◽  
Saad Zafar Usmani ◽  
Seema Singhal ◽  
Ajai Chari ◽  
...  
Keyword(s):  
Median Time ◽  
Alkylating Agents ◽  
Single Agent ◽  
Open Label ◽  
Prior Therapy ◽  
Duration Of Response ◽  
Grade 3 ◽  
International Multicenter Study ◽  
Line Of Therapy ◽  
Favorable Safety

LBA8512 Background: DARA, a human anti-CD38 IgG1κ mAb, has single agent activity and is well-tolerated in rel/ref MM (Lokhorst HM et al. ASCO 2014). This ongoing phase 2 study (NCT01985126) evaluated DARA monotherapy in the FDA breakthrough therapy designation population: MM patients with ≥ 3 prior lines of therapy including a proteasome inhibitor (PI) and an immunomodulatory agent (IMiD), or double refractory to a PI and IMiD. Preliminary results are reported. Methods: MMY2002 is a 2-part, open-label, international, multicenter study. In part 1 stage 1, 34 patients were randomized to DARA 8 mg/kg (n = 18) q4w or 16 mg/kg (n = 16) qw x 8 wk, q2w x 16 wk, then q4w in a Simon-2-stage design to determine the most effective dose. Subsequently, 90 additional patients were enrolled in the 16 mg/kg DARA group. The primary endpoint was overall response rate (ORR) by independent review (IRC). Results: Data for the 16 mg/kg DARA group are presented (n = 106). Baseline characteristics: median time since diagnosis, 4.8 y; median prior treatment lines, 5; 75% ISS ≥ 2. Refractory to: last line of therapy, 96%; last PI and IMiD, 95%; pomalidomide, 63%: carfilzomib, 48%; alkylating agents, 78%. Adverse events (AE; ≥ 20%) were fatigue (39.6%), anemia (33.0%), nausea (29.2%), thrombocytopenia (25.5%), back pain (22.6%), neutropenia (22.6%), cough (20.8%). Infusion-related reactions (IRR, 42.5%) were mainly grade 1/2 during first infusion (grade 3 4.7%; no grade 4). No patients discontinued study due to IRRs; 5 (4.7%) discontinued treatment due to AEs. None of these AEs were assessed by the investigator to be DARA-related. ORR (IRC assessed) was 29.2%, with 3 sCR, 10 VGPR, and 18 PR with a 7.4 month median duration of response. ORR was consistent across clinically relevant subgroups. Median time to progression was 3.7 months. Median overall survival has not been reached and the estimated 1-year OS rate is 65%. After a median follow up of 9.4 months 14/31 (45.2%) of responders remain on therapy. Conclusions: In a heavily pre-treated MM population (95% refractory to last PI and IMiD), DARA at 16 mg/kg showed meaningful durable single agent activity, with deep responses and a favorable safety profile. Clinical trial information: NCT01985126.

Pivotal DREAMM-2 study: Single-agent belantamab mafodotin (GSK2857916) in patients with relapsed/refractory multiple myeloma (RRMM) refractory to proteasome inhibitors (PIs), immunomodulatory agents, and refractory and/or intolerant to anti-CD38 monoclonal antibodies (mAbs).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 8536-8536 ◽  
Author(s):  
Sagar Lonial ◽  
Hans Chulhee Lee ◽  
Ashraf Badros ◽  
Suzanne Trudel ◽  
Ajay K. Nooka ◽  
...  
Keyword(s):  
Single Agent ◽  
Proteasome Inhibitors ◽  
Prior Therapy ◽  
Meaningful Activity ◽  
Common Grade ◽  
Duration Of Response ◽  
Independent Review ◽  
Grade 3 ◽  
Dose Modifications

8536 Background: Single-agent belantamab mafodotin (B-cell maturation antigen targeting immunoconjugate) showed clinically meaningful activity and manageable safety in patients with heavily pre-treated RRMM (DREAMM-2, NCT03525678, Lancet Oncol.2020). We report updated results (median follow-up 9 months). Methods: DREAMM-2 is an ongoing single-agent belantamab mafodotin (2.5 or 3.4 mg/kg) study in patients with RRMM after ≥3 prior therapy lines and refractory to an immunomodulatory agent, a PI, and refractory and/or intolerant to an anti-CD38 mAb. Primary endpoint: overall response rate (ORR; ≥partial response per independent review committee). Results: ORR was 31% in the 2.5 mg/kg (19% with ≥very good partial responses [VGPR]) and 35% (24% with ≥VGPR) in the 3.4 mg/kg groups (Table). Duration of response (DoR) was not reached (NR) in the 2.5 mg/kg and 6.2 months in the 3.4 mg/kg groups; 1-year overall survival (OS) estimate was 53%. Common Grade 3/4 AEs ( > 10% in either group) were keratopathy (2.5: 29%; 3.5: 24%), thrombocytopenia (2.5: 21%; 3.4: 32%), anemia (2.5: 20%; 3.4: 27%), pneumonia (2.5: 6%; 3.4: 13%), and neutropenia (2.5: 11%; 3.4: 16%). AEs were managed with dose delays (2.5: 54%; 3.4: 62%) and reductions (2.5: 34%; 3.4: 43%); discontinuations due to AEs were uncommon (2.5: 9%; 3.4: 12%). Conclusions: Single-agent belantamab mafodotin was well-tolerated, and clinically meaningful responses were sustained despite dose modifications with longer follow-up. Funding: GlaxoSmithKline (205678). Drug linker technology licensed from Seattle Genetics; monoclonal antibody produced using POTELLIGENT Technology licensed from BioWa. Clinical trial information: NCT03525678 . [Table: see text]

2-Chlorodeoxyadenosine treatment of low-grade lymphomas.

1992 ◽  
Vol 10 (3) ◽  
pp. 371-377 ◽  
Author(s):  
A C Kay ◽  
A Saven ◽  
C J Carrera ◽  
D A Carson ◽  
D Thurston ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Trial ◽  
Single Agent ◽  
Antineoplastic Agent ◽  
Lymphocytic Leukemia ◽  
Low Grade ◽  
Significant Activity ◽  
Prior Therapy ◽  
Significant Toxicity ◽  
Duration Of Response

PURPOSE Because of the need to identify effective new agents in the treatment of non-Hodgkin's lymphoma and because of the high activity of the purine analog 2-chlorodeoxyadenosine (2-CdA) against chronic lymphocytic leukemia and hairy cell leukemia, a phase II trial of 2-CdA was initiated in patients with low-grade lymphocytic lymphomas. PATIENTS AND METHODS Forty patients with low-grade lymphocytic lymphomas including diffuse small lymphocytic, follicular small-cleaved, and follicular mixed histologies were enrolled onto the study. Conventional therapies had failed in all patients, and six patients had lymph node biopsies showing evidence of histologic evolution to a higher-grade lymphoma. A total of 107 courses of 2-CdA were administered. There were 27 males and 13 females. The median age was 59 years (range, 37 to 80 years). Patients had received a median of three prior therapies (range, one to six therapies). RESULTS An overall response rate of 43% was achieved, with eight patients experiencing complete responses (CRs) and nine patients experiencing partial responses (PRs). The duration of responses ranged from 1 to greater than 33 months without maintenance therapy (median duration of response, 5 months). Histology and prior therapy history did not seem to correlate with responses. Significant toxicity was limited to bone marrow suppression; 18% of patients developed neutropenia, and 30% developed thrombocytopenia. CONCLUSIONS This phase II trial demonstrates that 2-CdA is an effective antilymphocyte, antineoplastic agent with significant activity as a single agent in patients with recurrent or refractory low-grade lymphocytic lymphoma. Responses were achieved with an acceptable toxicity profile. Further trials of this agent in previously untreated patients and in combination regimens are indicated and will be developed.

Assessment of sacituzumab govitecan (SG) versus treatment of physician’s choice (TPC) cohort by agent in the phase 3 ASCENT study of patients (pts) with metastatic triple-negative breast cancer (mTNBC).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 1077-1077
Author(s):  
Joyce O'Shaughnessy ◽  
Kevin Punie ◽  
Mafalda Oliveira ◽  
Filipa Lynce ◽  
Sara M. Tolaney ◽  
...  
Keyword(s):  
Single Agent ◽  
Objective Response ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Antibody Drug Conjugate ◽  
Phase 3 ◽  
Chemotherapy Agent ◽  
Recist 1.1 ◽  
Duration Of Response ◽  
Grade 3

1077 Background: In pts with pretreated mTNBC, standard-of-care chemotherapy is associated with low objective response rates (ORRs) and short median progression-free survival (PFS). SG is an antibody-drug conjugate composed of an anti–Trop-2 antibody coupled to the cytotoxic SN-38 payload via a proprietary, hydrolyzable linker. SG received accelerated FDA approval for treatment of pts with mTNBC who have received ≥2 prior therapies for metastatic disease. The confirmatory phase 3 ASCENT study (NCT02574455) in pts with relapsed/refractory mTNBC demonstrated a significant survival benefit of SG over TPC (median PFS: 5.6 vs 1.7 mo, HR 0.41, P< 0.0001; median overall survival [OS]: 12.1 vs 6.7 mo, HR 0.48, P< 0.0001) with a tolerable safety profile. Here we summarize efficacy results for SG vs each TPC agent in ASCENT to examine how each TPC agent performed individually. Methods: Pts had mTNBC refractory to or progressing after ≥2 prior standard chemotherapy regimens. Pts were randomized 1:1 to receive SG (10 mg/kg intravenously on days 1 and 8, every 21 days) or single-agent TPC (eribulin, vinorelbine, capecitabine, or gemcitabine). Primary endpoint was PFS per RECIST 1.1 by independent review in brain metastases-negative (BMNeg) pts. Secondary endpoints were ORR per RECIST 1.1, duration of response, OS, and safety. Outcomes for each of the agents in the TPC arm were analyzed and compared with SG. Results: Of 529 pts enrolled, 468 were BMNeg. Among pts in the TPC cohort (n = 233), eribulin was the most commonly chosen chemotherapy (n = 126), followed by vinorelbine (n = 47), capecitabine (n = 31), and gemcitabine (n = 29). Treatment with eribulin, vinorelbine, capecitabine, and gemcitabine resulted in shorter median PFS vs SG (2.1, 1.6, 1.6, and 2.7 vs 5.6 mo, respectively); similar results were observed for median OS (6.9, 5.9, 5.2, and 8.4 vs 12.1 mo), ORR (5%, 4%, 6%, and 3% vs 35%), and clinical benefit rate (CBR; 8%, 6%, 10%, and 14% vs 45%). Key grade ≥3 treatment-related adverse events (TRAEs) with TPC overall vs SG included neutropenia (33% vs 51%), leukopenia (5% vs 10%), fatigue (5% vs 3%), and anemia (5% vs 8%). Key grade ≥3 TRAEs with eribulin vs SG included neutropenia (30% vs 51%), leukopenia (5% vs 10%), fatigue (5% vs 3%), anemia (2% vs 8%), and peripheral neuropathy (2% vs none), respectively. The safety profiles of vinorelbine, capecitabine, and gemcitabine combined were consistent with that of TPC overall and with eribulin. One treatment-related death was reported for the TPC arm (eribulin) and none with SG. Conclusions: The efficacy benefit observed with SG vs TPC in pts with mTNBC was retained when evaluating each TPC chemotherapy agent individually. These results confirm that SG should be considered as a new standard of care in pts with pretreated mTNBC. Clinical trial information: NCT02574455 .

scholarly journals A Comparison of Death Domain-Associated Protein 6 in Different Endometrial Carcinomas Histotypes

2019 ◽  
Vol 14 ◽  
pp. 117727191986489
Author(s):  
Cao Jin ◽  
Sean Hacking ◽  
Miglena K Komforti ◽  
Mansoor Nasim
Keyword(s):  
Clear Cell ◽  
Point Mutations ◽  
Low Grade ◽  
Nuclear Staining ◽  
High Grade ◽  
Death Domain ◽  
Gynecology And Obstetrics ◽  
Grade 3 ◽  
Histologic Types ◽  
Endometrial Carcinomas

Background: Death domain-associated protein 6 (DAXX) is involved in regulating apoptosis via subcellular localization. The presence of DAXX point mutations correlates well with loss of nuclear expression on immunohistochemistry (IHC). In this study, we sought to determine (1) whether DAXX expression pattern is the same across different uterine carcinoma subtypes, and (2) which uterine carcinomas show loss of nuclear DAXX IHC. Design: We studied 65 uterine carcinomas of the following histologic types: 30 endometrioid (12 FIGO [The International Federation of Gynecology and Obstetrics] grade 1, 12 FIGO grade 2, and 6 FIGO grade 3), 8 serous, 14 clear cell, and 13 undifferentiated/dedifferentiated type (UEC/DDEC). Nuclear DAXX IHC was assessed in each tumor and was graded semi-quantitatively as follows: 0% to 50%, 50% to 75%, and greater than 75% of lesional cells react. Results: A total of 61% (25/41) of high-grade carcinomas (FIGO grade 3, serous, clear cell, and UEC/DDEC]) showed retained DAXX nuclear staining in >75% of lesional cells, compared with only 4.2% (1/24) of the low-grade carcinomas (FIGO grades 1 and 2) ( P = .0001), where DAXX expression was cytoplasmic. In addition, in the 11 DDEC cases, all the differentiated components showed loss of nuclear DAXX compared with the undifferentiated components which retained nuclear DAXX expression. Conclusions: We demonstrate that loss of nuclear DAXX is present in low-grade endometrial carcinomas and the differentiated components in UEC/DDEC, but not in high-grade ones, suggesting DAXX’s role in tumor progression and its potential as a therapeutic target in high-grade endometrial carcinomas.

Paclitaxel Is Safe and Effective in the Treatment of Advanced AIDS-Related Kaposi's Sarcoma

1999 ◽  
Vol 17 (6) ◽  
pp. 1876-1876 ◽  
Author(s):  
Parkash S. Gill ◽  
Anil Tulpule ◽  
Byron M. Espina ◽  
Suzanne Cabriales ◽  
Jocelyn Bresnahan ◽  
...  
Keyword(s):  
Treatment Failure ◽  
Median Duration ◽  
Systemic Therapy ◽  
Kaposi's Sarcoma ◽  
Single Agent ◽  
Kaposi’S Sarcoma ◽  
Duration Of Response ◽  
Previously Treated ◽  
Prior Systemic Therapy ◽  
Grade 3

PURPOSE: Liposomal anthracyclines are the present standard treatment for advanced AIDS-related Kaposi's sarcoma (KS). No effective therapies have been defined for use after treatment failure of these agents. A phase II trial was thus conducted with paclitaxel in patients with advanced KS to assess safety and antitumor activity. MATERIALS AND METHODS: A regimen of paclitaxel at a dose of 100 mg/m2 was given every 2 weeks to patients with advanced AIDS-related KS. Patients were treated until complete remission, disease progression, or unacceptable toxicity occurred. RESULTS: Fifty-six patients with advanced AIDS-related KS were accrued. Tumor-associated edema was present in 70% of patients and visceral involvement in 45%. Forty patients (71%) had received prior systemic therapy; 31 of these were resistant to an anthracycline. The median entry CD4+ lymphocyte count was 20 cells/mm3 (range, 0 to 358). A median of 10 cycles (range, 1 to 54+) of paclitaxel was administered. Fifty-nine percent of patients showed complete (n = 1) or partial response (n = 32) to paclitaxel. The median duration of response was 10.4 months (range, 2.8 to 26.7+ months) and the median survival was 15.4 months. The main side effects of therapy were grade 3 or 4 neutropenia in 61% of patients and mild-to-moderate alopecia in 87%. CONCLUSION: Paclitaxel at 100 mg/m2 given every 2 weeks is active and well tolerated in the treatment of advanced and previously treated AIDS-related KS. The median duration of response is among the longest observed for any regimen or single agent reported for AIDS-related KS. Paclitaxel at this dosage and schedule is a treatment option for patients with advanced AIDS-related KS, including those who have experienced treatment failure of prior systemic therapy.

Results of a phase 2 study of bortezomib in patients with relapsed or refractory indolent lymphoma

Blood ◽  
2010 ◽  
Vol 115 (3) ◽  
pp. 475-480 ◽  
Author(s):  
Nicholas Di Bella ◽  
Raymond Taetle ◽  
Kathryn Kolibaba ◽  
Thomas Boyd ◽  
Robert Raju ◽  
...  
Keyword(s):  
Median Time ◽  
Single Agent ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Complete Response ◽  
Low Grade ◽  
Free Survival ◽  
Ann Arbor ◽  
Duration Of Response ◽  
Unconfirmed Complete Response

Abstract This study evaluated the efficacy and safety of single-agent bortezomib in indolent B-cell lymphoma that had relapsed from or was refractory to rituximab. Sixty patients enrolled: 59 were treated with bortezomib 1.3 mg/m2 on days 1, 4, 8, and 11 for up to eight 21-day cycles; responders could receive 4 additional cycles; maintenance was optional. Fifty-three evaluable patients completed more than 2 cycles. The median age was 70 years, 53% female, Ann Arbor stage III-IIIE (28%) and IV (65%); 43 patients (72%) had more than 2 prior regimens; and 6 patients went on to maintenance. Overall responses are as follows: 1 complete response (1.9%), 3 unconfirmed complete response (5.7%), 3 partial response (5.7%), 34 stable disease (64.2%), and 12 progressive disease (22.6%). Median time to response = 2.2 months (range, 1.2-5.3 months); duration of response = 7.9 months (2.8-21.3 months); 1-year survival was 73% and 2-year survival was 58%; median survival = 27.7 months (range, 1.4-30.9 months); median progression-free survival = 5.1 months (range, 0.2-27.7 months), median time to progression = 5.1 months (range, 0.2-27.7 months), and median event-free survival = 1.8 months (range, 0.2-27.7 months). Treatment-related grade 3 or 4 adverse events included: thrombocytopenia (20%), fatigue (10%), neutropenia (8.5%), and neuropathy and diarrhea (6.8% each). This study demonstrates that bortezomib has modest activity against marginal zone and follicular lymphoma; it has the potential for combination with other agents in low-grade lymphomas. Maintenance therapy should be explored further.

Trisenox® (arsenic trioxide) in Patients with Myelodysplastic Syndromes (MDS): Preliminary Results of a Phase I/II Study.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1433-1433
Author(s):  
Norbert Vey ◽  
Francois Dreyfus ◽  
Agnes Guerci ◽  
Pierre Fenaux ◽  
Herve Dombret ◽  
...  
Keyword(s):  
Phase I ◽  
Arsenic Trioxide ◽  
Lower Risk ◽  
Single Agent ◽  
Clinical Activity ◽  
Molecular Response ◽  
Improvement Rate ◽  
Preliminary Results ◽  
Duration Of Response ◽  
Grade 3

Abstract Introduction: Single-agent Trisenox® (arsenic trioxide) induces high hematologic and molecular response rates leading to prolonged survival in patients with relapsed/refractory acute promyelocytic leukemia. Arsenic trioxide exhibits multifaceted mechanisms of action, including induction of tumor cell differentiation, apoptosis, and angiogenesis inhibition. Recent reports have documented the clinical activity of arsenic trioxide in MDS patients, leading to improvements in hematologic parameters and to transfusion independence or reduction. We report preliminary results of an ongoing European multicenter phase I/II study of arsenic trioxide in MDS patients. Patient eligibility includes all FAB categories with &lt;30% blasts. Final results of the study will be reported. Methods: Arsenic trioxide is given as a 1-hr IV infusion, loading dose of 0.30 mg/kg/day for 5 days, and maintenance with 0.25 mg/kg/day 2X a week for &gt;15 weeks. Disease assessments are every 8 weeks, by modified IWG response criteria. Patients: 105 patients have been enrolled: median age is 67 years (range 31–89), median time from diagnosis to 1st dose is 10.9 months (range 0.2–117.6). 101 patients have received drug and have been evaluated (78M/23F). 39 patients have IPSS lower-risk (LR: low and Int-1) and 62 have higher-risk (HR: high and Int-2) MDS. FAB categories are RA (9 patients), RARS (11), RAEB (62), RAEB-t (13), and CMML (6). 86 patients were transfusion dependent at baseline. Results: Responses were observed in 27 evaluable patients (27%). They include 1 CR (1%), 20 major Hematologic Improvements (HI: 20%) and 6 minor HI (6%). Responses were seen across the 3 lineages: major HI-Erythroid: 11; major HI-Neutrophil: 8 (including 2 also HI-E); and major HI-Platelet: 6 (including 3 also HI-E). The hematologic improvement rate among LR patients was 9/39 (23%) and among HR patients, 18/62 (29%, including the CR). 14 patients became transfusion independent and an additional 7 patients had transfusions reduced by ≥50%. Responses were seen after 1–3 months of treatment, and median duration of response is 4+ months at this time. The true duration of response is not yet known, as 20 patients were still responding at their most recent assessments. Arsenic trioxide toxicity was manageable and mostly mild; 4 patients had treatment-related grade 3 febrile neutropenia and 1 patient each experienced grade 3 and grade 4 thrombocytopenia. One had grade 4 neutropenia; the only other grade 4 toxicity was 1 pulmonary edema. An additional 14 patients each had a different grade 3 event. QTc prolongation was reported in only 1 patient, who had 2 isolated episodes that were considered clinically insignificant and did not result in treatment delay. No patient had alopecia or severe nausea or vomiting. Summary and Conclusions: These preliminary results indicate that arsenic trioxide is generally well tolerated, even by elderly patients, and that it induces responses in all three hematopoietic lineages, in similar proportions of patients with higher risk and with lower risk MDS. 14 of 86 transfusion-dependent patients became transfusion independent. Final results of the study will be presented.

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