Venetoclax induces sustained complete responses in refractory/relapsed patients with cardiac AL amyloidosis.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e19538-e19538 ◽  
Author(s):  
Fabien Le Bras ◽  
Jehan Dupuis ◽  
François Lemonnier ◽  
Silvia Oghina ◽  
Diane Bodez ◽  
...  
Keyword(s):  
Therapeutic Option ◽  
Influenza Infection ◽  
Single Agent ◽  
Complete Response ◽  
Median Number ◽  
Al Amyloidosis ◽  
Duration Of Treatment ◽  
Systemic Involvement ◽  
Academic Center ◽  
Heavily Pretreated

e19538 Background: Venetoclax (VEN) is an orally bioavailable small molecule inhibitor of the anti-apoptotic protein BCL-2 and has been shown to have efficacy against myeloma (MM), particularly in patients that harbor t(11;14). Approximately, 50% of AL amyloidosis patients will exhibit t(11;14) making VEN an attractive therapeutic option. Methods: We here report the results of a retrospective analysis of a monocentric series of refractory/relapsed (R/R) patients (pts) heavily pretreated with cardiac AL amyloidosis treated in a french academic center. VEN was given daily alone or in association with dexamethasone (DEX), with or without bortezomib (BTZ). Treatment was planned to be administered until progression. Results: Between February 2017 and January 2019, 7 consecutive R/R pts have been treated. All had received previous BTZ and daratumumab (DARA) containing regimen. Baseline characteristics were: median age: 72.7 years (range 40-84), Mayo Clinic stage: stage I in 2 pts, stage II in 3 and stage IIIA in 2. All patients but one had in addition to cardiac deposit, systemic involvement including kidney, joint, neurologic, gastro-intestinal tract, lymph node and muscle. All but one pts were refractory to their last treatment consisting of DARA-DEX with or without IMID. The t(11;14) translocation was present in 5 pts, absent in 1 and undetermined in 1 pts. Two pts had concomitant MM at diagnosis. Median number of previous line treatments was 4 (3-5). Five patients received VEN- BTZ- DEX as described in MM (PMID: 28847998), 1 with DEX and 1 as monotherapy. Five pts received 400 mg/d, one 200 mg/d and one 100 mg/d. Median duration of treatment was 76 days (30-713). All patients but one are still on treatment. One patient treated with 400 mg/d had a dose reduction to 100 mg/d due to grade 2 diarrhea. Four patients received at least 2 cycles and were evaluable for response. One 84 y old patient in stable disease after 1 cycle died due to influenza infection. 2 patients received only one cycle of treatment. Hematological complete response occurred in 2/4 (50%) patients, after 63 and 27 days. Interestingly, responses were sustained as the 2 responders were still on therapy after 76 and 713 days. This later patient, refractory to 2 previous lines had a cardiac and neurologic response. The 2 responding patients had proven t(11:14). Conclusions: On this limited series of heavily pretreated patients with R/R AL cardiac amyloidosis VEN used as a single agent or in combination can induce prolonged response and seems a promising drug with an acceptable safety profile in patients with t(11;14).

Subcutaneous alemtuzumab in patients with refractory/relapsed B-CLL after a fludarabine-based regimen

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 6600-6600
Author(s):  
R. Bezares ◽  
G. Stemmelin ◽  
D. Argentieri ◽  
E. Lanari ◽  
E. Guy-Garay ◽  
...  
Keyword(s):  
Interim Analysis ◽  
Residual Disease ◽  
Single Agent ◽  
Complete Response ◽  
Median Number ◽  
Duration Of Treatment ◽  
Barr Virus ◽  
Epstein Barr ◽  
Grade 3 ◽  
Cmv Disease

6600 Background: Alemtuzumab is the only immunotherapy that is effective as a single agent in patients with B-CLL who are refractory to, or who have relapsed after, fludarabine therapy. The optimized schedule for alemtuzumab that achieves maximal efficacy with manageable toxicity is still being explored. We report the first interim analysis of a new, less intensive schedule of alemtuzumab SC to patients with refractory/relapsed B-CLL. Methods: Alemtuzumab was dose escalated from 10 to 20 mg during the first week, 30 mg bid during the second and third weeks, and 30 mg once weekly during weeks 4, 6, 8, 10, 12, 16, 20, 24, 28, 34, and 40. Antiviral prophylaxis included TMP/SMX bid 3 times a week and acyclovir 200 mg tid. Results: Patients (N = 36) with refractory (19%) or relapsed (81%) B-CLL had a median age of 67 years (range, 43–86 years), 28 were male, 61%/39% had Binet stage B/C disease, and 2 had B-cell prolymphocytic transformation. The median number of prior therapies was 1 (range, 1–4). The median duration of treatment was 7 weeks (range, 2–24 weeks), with a median cumulative alemtuzumab dose of 412 mg (range, 150–1,080 mg). Thirty-two patients were evaluable for response. The overall response rate of 93%: complete response (CR), 34%; unconfirmed CR, 6%; partial response (PR), 53%. Two patients (7%) did not respond to therapy. Of the 7 refractory patients, 5 had a PR, 1 did not respond, and 1 was not yet evaluable. Median overall survival was 10 months, which correlated with response and pretreatment status. Minimal residual disease (MRD) was measured by flow cytometry in 5 patients who achieved a CR: 3 patients had <0.5% of CD5/CD19/CD23+ cells, 1 patient had <5% of CLL cells, and 1 patient had <10% CLL cells. According to WHO toxicity criteria, 5 patients experienced grade 3/4 infection; 2 patients had grade 3 granulocytopenia/thrombocytopenia; 1 patient had cytomegalovirus (CMV) reactivation without CMV disease; and 1 patient developed Epstein-Barr Virus with prolonged bone marrow hypoplasia. Conclusions: Results of this interim analysis suggest that a less intense regimen of alemtuzumab is feasible, effective, and safe for patients with refractory/relapse B-CLL after fludarabine therapy. No significant financial relationships to disclose.

A large multicentric study of gemcitabine-based regimen in relapsed or refractory Hodgkin lymphoma (HL) patients (pts)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 18518-18518
Author(s):  
P. Validire ◽  
C. Fermé ◽  
P. Brice ◽  
M. Diviné ◽  
J. Gabarre ◽  
...  
Keyword(s):  
Initial Dose ◽  
Soft Tissues ◽  
Univariate Analysis ◽  
Single Agent ◽  
Complete Response ◽  
Median Number ◽  
Multicentric Study ◽  
Chemotherapeutic Regimen ◽  
Heavily Pretreated ◽  
One Year

18518 Background: The aim of this study was to assess the efficacy and safety of gemcitabine-based regimen in heavily pretreated HL pts. Methods: Relapsed or refractory HL pts treated with gemcitabine were retrospectively reviewed. Gemcitabine was used as a single agent or administered in combination with vinorelbine, oxaliplatine, doxorubicine, vinblastine, rituximab, and/or corticosteroids. Results: Fifty-five pts treated in 9 departments of clinical hematology between January 1999 and August 2006 were included in the study. Initial characteristics before gemcitabine administration were: nodular sclerosis in 84%; sex ratio M/F 1.1; median age 29 years (range: 15–85 years); advanced stage 84%; extranodal sites were lung, bone, liver, soft tissues, and bone marrow in 68%, 31%, 13%, 21%, and 4%, respectively; Hasenclever index lower than 3 in 20/43 cases (47%). At the end of the first front-line therapy (chemotherapy ± radiotherapy), 19 pts (35%) were in complete response (CR) in whom 13 relapsed within one year, 5 were in partial response (PR), and 31 pts were primary refractory (56%). Median number of previous chemotherapeutic regimen was 3 (range 1–8), 39 pts (71%) have received radiotherapy (RT), and 34 pts (62%) one or two autologous/allogenic stem cell transplantations (A/ASCT). Twenty-nine pts received gemcitabine alone with a median initial dose per injection of 750 mg/m2 (range: 180–1250 mg/m2); Gemcitabine was administered at an initial dose per injection of 1000 mg/m2 (range: 500–1250) in combination with vinorelbine in 10 pts, oxaliplatine in 13 pts in whom 4 with rituximab, and with others drugs in 3 pts. In both cases, the median number of combined gemcitabine regimen injections was 6 (range: 1–27). Toxicity was mainly hematological (75% of pts developed bi- or pancytopenia) or infectious (13%). Among all included pts, 6 were in CR (11%) and 5 in PR with an overall response rate of 20%. Among the 6 CR, 5 pts received thereafter A/ASCT and 2 pts RT, with 2 persistent CR at 16 and 44 months. In univariate analysis, none prognostic factor for response to gemcitabine was identified. Conclusions: This study, which constitutes one of the most important series, showed a mild efficacy of gemcitabine-based regimen in heavily pretreated HL patients. No significant financial relationships to disclose.

Efficacy of Risk Adapted Cyclophosphamide, Thalidomide and Dexamethasone in Systemic AL Amyloidosis.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3496-3496
Author(s):  
Ashutosh D. Wechalekar ◽  
Hugh J.B. Goodman ◽  
Julian D. Gillmore ◽  
Helen J. Lachmann ◽  
Mark Offer ◽  
...  
Keyword(s):  
Heart Failure ◽  
Dose Reduction ◽  
Survival Data ◽  
Standard Dose ◽  
Single Agent ◽  
Response Rates ◽  
Complete Response ◽  
Median Number ◽  
Al Amyloidosis ◽  
Starting Dose

Abstract The prognosis for advanced AL amyloidosis (AL) with conventional treatment remains very poor and stem cell transplantation has unacceptably high mortality (TRM). Single agent thalidomide in standard doses is poorly toleranated and has low response rates in AL (Dispenzieri et al, Amyloid10:247; 2003) and few data on the role of thalidomide based combination chemotherapy in AL are available. We report experience with a risk adapted thalidomide based combination using cyclophosphamide and dexamethasone (CTD) in 43 patients with AL amyloidosis at the National Amyloidosis Centre, UK. The regime (adapted from the UK MRC Myeloma IX trial) consisted of a 21-day cycle oral cyclophosphamide 500mg once weekly, thalidomide 200mg/day (starting dose 100mg/day, increased after 4 weeks if tolerated) continuously and dexamethasone 40mg days 1–4 and 9–12. This was risk attenuated (CTDa) in the elderly (&gt;70yrs), heart failure &gt;NYHA grade II or significant fluid overload to a 28-day cycle of cyclophosphamide 500mg days 1, 8 and 15, thalidomide 200mg/day (starting dose 50mg/day, 4–weekly 50mg increments as tolerated), and dexamethasone 20mg day 1–4 and 15–18. A total on 43 patients (22M:21F, median age 61yrs, range 43–79) were treated; 35 received CTD and 8 received CTDa. Median number of organs involved was 2 (1–4), including renal in 62% of patients, cardiac in 60%, hepatic in 39%. Median follow-up from treatment initiation was 7mo (0.4–35) and from diagnosis 16.5mo (0.6–69). Patients received a median of 4 cycles of treatment (1–7). The number of previous treatments was none in 39%, one in 39%, two in 14% and three in 6%. Toxicities were seen in 17 (39%) of patients (CTDa 3; CDT 14) necessitating dose reduction in 11 (25%), dexamethasone omission in 6 (14%), thalidomide omission in 1 (2%) and complete regime discontinuation in 4 (9%). The main side effects were: worsening heart failure 20%, neuropathy 11%, infections 11%, sleepiness 2%, and neutropenia, renal impairment, constipation and fatigue − 4% each with no thrombotic complications or TRM. Survival data was evaluable in all patients while response was evaluable in 35 (81%).Haematologic response was defined as follows: complete response (CR) - sustained normalisation of sFLC (serum free light chains) ratio, partial response (PR) - sustained ≥50% reduction in pre-treatment clonal isotype. There was a haematologic response in 26 (74%). 12 (34%) has a CR, 14 (40%) had a PR, 9 (25%) had no response. sFLC assays were available after every cycle in 27pts; a reduction in the clonal class of ≥25% was evident within 30days in 59% and in another 33% by day 60. An appreciable regression of amyloid was evident in 15% of the responders by SAP scintigraphy. The median survival for the cohort has not been reached at 36 months. This preliminary study shows excellent efficacy of CTD in patients with advanced AL with response rates superior to conventional intermediate dose chemotherapy. The regime appears to be safe with no treatment related mortality and tolerance appears to be better than than standard dose thalidomide alone (Dispenzieri et al, Amyloid10:247; 2003) or with dexamethasone (Pallidini et al, Blood105:7;2005). However, a quarter of the patients needed dose reduction and more stringent use of risk adaptation may improve the tolerability of this regime. Risk adapted CTD may be an alternative to standard therapies as front line treatment in AL amyloidosis.

Bendamustine Treatment in Refractory or Relapsed T Cell Lymphomas: A Retrospective Multicenter Study

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1505-1505
Author(s):  
Emilie Reboursiere ◽  
Fabien Le Bras ◽  
Franck Morschhauser ◽  
Emmanuel Gyan ◽  
Aline Clavert ◽  
...  
Keyword(s):  
T Cell ◽  
Disease Progression ◽  
Single Molecule ◽  
Therapeutic Option ◽  
Single Agent ◽  
Progression Free Survival ◽  
Complete Response ◽  
Median Number ◽  
Biological Data ◽  
Advisory Boards

Abstract Peripheral T-cell lymphoma (PTCL) is an aggressive disease with poor outcome. First line therapies are usually unsatisfactory with frequent need for second-line therapies. Median progression free survival (PFS) and overall survival (OS) for relapse PTCL patients are very short with few available therapeutic options. Bendamustine has been shown to be effective in this setting. In order to assess the efficacy of bendamustine outside clinical trials, we conducted a national retrospective study of patients with the diagnosis of PTCL and who were treated with bendamustine. Between 2011 and 2013, about 200 patients with the diagnosis of PTCL have been treated in 27 centers with bendamustine. We present the results of 142 patients with complete clinical and biological data. The population median age was 64y (range 28-89) with male/female sex ratio of 1,4 (83/59). Histologies were: angio-immunoblastic (AILT=63), PTCL-NOS (n=44), anaplasic-large (ALCL=13), NK/TCL (n=3), mycosis fungoides (MF=7), subcutaneous panniculitis-like-TCL (n=2), hepato-splenic-TCL (n=1) and others (n=9). The majority of patients (96%, n=130) had stage-disseminated disease and 72% (n=102) of them had extranodal localisations. The median number of chemotherapy lines prior to bendamustine was 2 (range 0-8). Seven patients (5%) had received allogeneic stem cells transplantation (SCT) and 16 autologous SCT (11%) prior to bendamustine. The median duration of response (DoR) after the last prior to bendamustine chemotherapy was 4.3 months (range 1-70) and 50% of patients had refractory disease at bendamustine treatment. Seventy-four patients (52%) received less than 3 cycles, mostly because of disease progression. Overall, they received a median of 2 cycles (range 1-8) with a median dose of 90mg/m2 (range 50-150). The best overall response rate (ORR) was 32% (45/141) with complete response of 24% (CR=34). The median DoR was 3.3 months (1-39). For AITL patients, ORR was 52% (33/63) with CR of 41%, whereas it was 18% (8/44) with 11% of CR, in patients with PTCL-nos, respectively (p=0.01). Nine patients (6%) received allogeneic SCT in CR. Median PFS was 3 months (range 0.2-46.3) and median OS was 4.4 months (range 0.2-55.4). On multivariate analysis, chemotherapy refractory (p=0.001) patients' and extranodal disease localization (p=0.028) before bendamustine influenced adversely the ORR. With a median follow up 4.4 months, 72% of patients (102/142) died. The most frequent cause of death were: disease progression (92%) or toxicities (6%). Grade 3-4 thrombocytopenia, neutropenia and infections were reported in 22%, 17% and 23% of cases, respectively. Bendamustine as single agent must be considered as a therapeutic option for relapsed or refractory PTCL, particularly in patients with AITL. The safety profile was good. Combination of bendamustine with other drugs should be evaluated prospectively. Disclosures Off Label Use: Bendamustine, single molecule, alkylant agent with antimetabolite properties. Morschhauser:Genentech Inc./Roche: Other: Advisory boards. Cartron:Sanofi: Honoraria; GSK: Honoraria; Celgene: Honoraria; Gilead: Honoraria; Roche: Consultancy, Honoraria.

scholarly journals Phase II trial of 2-chlorodeoxyadenosine for the treatment of cutaneous T-cell lymphoma [see comments]

Blood ◽  
1996 ◽  
Vol 87 (3) ◽  
pp. 906-911 ◽  
Author(s):  
TM Kuzel ◽  
A Hurria ◽  
E Samuelson ◽  
MS Tallman ◽  
HH Jr Roenigk ◽  
...  
Keyword(s):  
Median Duration ◽  
Group Performance ◽  
Performance Status ◽  
Single Agent ◽  
Eastern Cooperative Oncology Group ◽  
Complete Response ◽  
Median Number ◽  
Infectious Complications ◽  
Hematologic Toxicity ◽  
Heavily Pretreated

We investigated the efficacy of 2-chlorodeoxyadenosine (2-CdA) therapy in patients with mycosis fungoides (MF) and the Sezary syndrome (SS). Between February 1991 and November 1993, 21 patients with relapsed or refractory MF/SS were treated with 2-CdA. 2-CdA was administered by continuous intravenous infusion at a dose of 0.1 mg/kg/d for 7 days initially (13 patients), but was subsequently reduced to 5 days (nine patients) due to hematologic toxicity. All patients had failed to respond to at least one prior treatment for MF/SS (median number of total prior therapies, five; median number of systemic prior therapies, three) and had an Eastern Cooperative Oncology Group performance status of two or better. Cycles were administered at 28-day intervals. Assessable patients received at least 5 days of 2-CdA. Fourteen patients received more than one cycle of 2-CdA. An overall response rate of 28% was achieved. Three patients (14%) had a complete response with a median duration of 4.5 months (range, 2.5 to 16). Three (14%) had a partial response with a median duration of 2 months (range, 2 to 4). Fifteen patients (72%) had no response. The most significant toxicities encountered were bone marrow suppression (62% of patients) and infectious complications (62% of patients). Thirty-eight percent of patients experienced no toxicity from 2-CdA. 2-CdA has activity as a single agent in patients with previously treated relapsed MF/SS. Studies in less heavily pretreated individuals with 2-CdA alone or in combination will be undertaken.

scholarly journals Long-Term Outcomes and Responses to Retreatment in Patients With Melanoma Treated With PD-1 Blockade

2020 ◽  
Vol 38 (15) ◽  
pp. 1655-1663 ◽  
Author(s):  
Allison Betof Warner ◽  
Jessica S. Palmer ◽  
Alexander N. Shoushtari ◽  
Debra A. Goldman ◽  
Katherine S. Panageas ◽  
...  
Keyword(s):  
Treatment Failure ◽  
Single Agent ◽  
Multivariable Analysis ◽  
Complete Response ◽  
Median Number ◽  
Long Term Outcomes ◽  
Duration Of Treatment ◽  
Unresectable Stage

PURPOSE To analyze long-term outcomes after treatment discontinuation of anti–programmed death-1 (anti–PD-1) therapy in a cohort of patients with melanoma with the longest follow-up yet available to our knowledge, including a majority of patients treated outside of a clinical trial. We also assessed efficacy of retreatment with anti–PD-1 therapy with or without ipilimumab in relapsing patients. METHODS We retrospectively analyzed all patients with nonuveal, unresectable stage III/IV melanoma treated with single-agent anti–PD-1 therapy at Memorial Sloan Kettering from 2009-2018 who had discontinued treatment and had at least 3 months of follow-up after discontinuation (n = 396). Overall survival for patients with complete response (CR) was calculated from time of CR. Time to treatment failure for patients with CR was time from CR to the next melanoma treatment or death. RESULTS CRs were seen in 102 of 396 patients (25.8%). The median number of months of treatment after CR was zero (range, stopped before CR to 26 months after CR). With a median follow-up of 21.1 months from time of CR in patients who did not relapse, the probability of being alive and not needing additional melanoma therapy at 3 years was 72.1%. There was no significant association between treatment duration and relapse risk. In multivariable analysis, CR was associated with M1b disease and cutaneous versus mucosal or acral primaries. Among the 78 patients (of 396) retreated after disease progression, response was seen in 5 of 34 retreated patients with single-agent anti–PD-1 therapy and 11 of 44 patients escalated to anti–PD-1 plus ipilimumab. CONCLUSION In our cohort, most patients discontinued treatment at the time of CR. Most CRs were durable but the probability of treatment failure was 27% at 3 years. Responses to retreatment were infrequent. The optimal duration of treatment after CR is not yet established.

Complete responses to two different anti-PD1 agents in a metastatic melanoma patient

2019 ◽  
Vol 26 (2) ◽  
pp. 496-499 ◽  
Author(s):  
Saadettin Kilickap ◽  
Deniz C Guven ◽  
Oktay H Aktepe ◽  
Burak Y Aktas ◽  
Omer Dizdar
Keyword(s):  
Metastatic Melanoma ◽  
Checkpoint Inhibitors ◽  
Real Life ◽  
Complete Response ◽  
Duration Of Treatment ◽  
Treatment Protocols ◽  
Real Life Data ◽  
Heavily Pretreated ◽  
Drug Free

In the last decade, immune checkpoint inhibitors changed the landscape of metastatic melanoma. However, the optimal duration of treatment and treatment cessation in responders is largely unknown. Herein, we represent a heavily pretreated metastatic melanoma case who had a complete response to pembrolizumab and also a complete response with nivolumab after progression during drug-free follow-up. We think that reinduction with a different anti-PD1 antibody may be used in patients with metastatic melanoma responders. Clinical trials with prespecified sequential treatment protocols and large real-life data can further delineate this subject.

Phase III Trial of Pixantrone Dimaleate Compared with Other Agents as Third-Line, Single-Agent Treatment of Relapsed Aggressive Non-Hodgkin's Lymphoma (EXTEND): Results From the Treatment and Follow-up Periods.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1677-1677 ◽  
Author(s):  
Ruth Pettengell ◽  
Bertrand Coiffier ◽  
Geetha Narayanan ◽  
Fernando Hurtado de Mendoza ◽  
Raghunadharao Digumarti ◽  
...  
Keyword(s):  
Treatment Group ◽  
Primary Endpoint ◽  
Safety Profile ◽  
Single Agent ◽  
Median Number ◽  
Phase 3 ◽  
Comparator Group ◽  
Duration Of Response ◽  
Heavily Pretreated

Abstract Abstract 1677 Poster Board I-703 Introduction Nearly half of patients with aggressive non-Hodgkin's lymphoma (NHL) relapse or are refractory to initial therapy. With each subsequent therapy, the probability of response decreases and the responses are less durable. An agent currently in development, pixantrone dimaleate (pixantrone), is a novel aza-anthracenedione structurally similar to mitoxantrone and anthracyclines. The clinical activity and safety profile of pixantrone are promising in patients heavily pretreated for relapsed aggressive NHL and who received prior treatment with up to 450 mg/m2 of doxorubicin. Patients and Methods This phase 3, randomized, multicenter, controlled, open-label study enrolled patients who had ≥1 prior anthracycline-containing regimen and failed 2 prior treatment regimens for relapsed aggressive (de novo or transformed) NHL. Seventy patients were randomized to a treatment group administered pixantrone 85 mg/m2 on days 1, 8, and 15 of a 28-day cycle, for up to 6 cycles. Seventy patients were randomized to the investigator's choice of a single-agent comparator (vinorelbine, oxaliplatin, ifosfamide, etoposide, or mitoxantrone; in the US only, gemcitabine and rituximab were permitted). Patients in both groups were followed up to 18 months after last treatment. The primary endpoint, CR/CRu rate, was assessed by an independent assessment panel (IAP). Other efficacy endpoints were overall response rate (ORR), responses lasting ≥4 months, progression-free survival (PFS), overall survival (OS), duration of response, and time to response. This report includes the results from the treatment period and updated results from the follow-up period, which is still ongoing. Results A total of 140 patients were randomized with 70 patients in each treatment group. Of the 140 patients, 96% received treatment (n=68 for pixantrone, n=67 for comparator). The median number of treatment cycles that patients in the pixantrone group received was 4 compared with 3 for the comparator group. The percentage of patients who received all 6 treatment cycles in the pixantrone group was 32.4% compared with 28.4% for the comparator. The primary endpoint, CR/CRu rate (assessed by IAP), in the ITT population was 20.0% for the pixantrone group compared with 5.7% for the comparator (P = 0.021). The ORR for the pixantrone group was 37.1% compared with 14.3% for the comparator (P = 0.003), and the percentage of patients with objective responses lasting at least 4 months for the pixantrone group was 25.7% compared with 8.6% for the comparator (P =0.012). The median number of months of PFS in the pixantrone group was 4.7 compared with 2.6 for the comparator (HR= 0.60, log rank P = 0.007). The median number of months of OS, while not fully mature, was 8.1 for the pixantrone group compared with 6.9 for the comparator (HR=0.88, log rank P = 0.554). Subgroup assessments of the CR/CRu rate and ORR, by risk factor, were consistently higher in the pixantrone group than in the comparator group. These subgroup assessments included prior exposure to anthracyclines ('300 mg/m2 or ≥300 mg/ m2) and rituximab (treated or not treated), IPI score ('1 or ≥2), and NHL diagnosis (refractory or relapsed), and age ('65 or ≥65). In the pixantrone group, neutropenia and leukopenia were the most common (≥10%) grade 3/4 adverse events and the incidence of febrile neutropenia was 7.4%. The percentage of patients with cardiac disorder SAEs was 8.8% in the pixantrone group compared with 4.5% for the comparator. Conclusions In this phase 3, randomized, multicenter study, patients with relapsed aggressive NHL administered single-agent pixantrone achieved superior efficacy, compared with other single-agent chemotherapeutic agents, as measured by CR/CRu rate, ORR, responses lasting ≥4 months, and PFS. Positive trends were observed in OS and duration of response. Patients in the pixantrone group tended to reach CR sooner than patients in the comparator group. Pixantrone has a tolerable safety profile in heavily pretreated patients with relapsed aggressive NHL. Disclosures Cernohous: Cell Therapeutics, Inc: Employment. Wang:Cell Therapeutics, Inc: Employment. Singer:Cell Therapeutics, Inc: Employment.

Initial Results of PX-171-003, An Open-Label, Single-Arm, Phase II Studyof Carfilzomib (CFZ) in Patients with Relapsed and Refractory Multiple Myeloma (MM)

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 864-864 ◽  
Author(s):  
Sundar Jagannath ◽  
Ravi Vij ◽  
A. Keith Stewart ◽  
George Somlo ◽  
Andrzej Jakubowiak ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Phase 1 ◽  
Single Agent ◽  
Proteasome Inhibition ◽  
Complete Response ◽  
Open Label ◽  
Upper Respiratory Infection ◽  
Heavily Pretreated ◽  
Clinical Benefit Response ◽  
High Level

Abstract Background: Carfilzomib (CFZ) is a novel proteasome inhibitor of the epoxyketone class that exhibits a high level of selectivity for the proteasome and has been shown in a phase 1 study to result in greater than 80% proteasome inhibition on a QDx2 consecutive day schedule. We piloted this agent in MM patients with relapsed and refractory disease, who had failed bortezomib (BTZ) and at least one immunomodulatory (IMiD) agent, e.g., thalidomide (THAL) and/or lenalidomide (LEN). Methods: PX-171-003 is an open-label, multicenter study enrolling pts with MM who have relapsed from at least 2 prior therapies and who are refractory; defined as progressing on or within 60 days of last therapy or<25% response to the last therapy. Pts received CFZ 20 mg/m2 IV Days 1, 2, 8, 9, 15 and 16 every 28 days, for up to 12 cycles. Dexamethasone 4 mg po was administered prior to each dose in Cycle 1. Responses were evaluated by the International Uniform Response Criteria for Multiple Myeloma. Clinical benefit response (CBR) was defined as complete response (CR) + partial/very good partial response (PR/VGPR) + minimal response (MR, as defined by EBMT criteria). Responses were adjudicated by an independent review committee. Results: 46 pts were enrolled, including 78% with progression on or within 60days of last therapy and 22% with no response to last therapy. 39 pts initiated treatment, completed at least one cycle of CFZ, had measurable M-protein, and were evaluable (eval) for response. The mean number of prior therapies (excluding transplant) was 6.4(range 1 to 18). 100% of pts received prior BTZ, 91% prior THAL, 89% prior LEN, and 83% prior stem cell transplantation (SCT). To date, pts received a median of 3 cycles(range 1–9) of CFZ; 22 started at least 4 cycles. The CBR was 26% (10/39 eval pts), including 5 pts achieving PR, 5 pts achieving MR, and 16 additional patients achieving stable disease (SD). Time to response was rapid, frequently occurring in the 1st cycle. CFZ was generally well tolerated; the most common adverse events (AEs) were fatigue(65%), nausea (37%), upper respiratory infection (37%), and diarrhea (33%). Worsening of hematologic parameters: anemia (65%); thrombocytopenia (46%) and neutropenia(20%) were predominantly Grades 1 and 2. Increased creatinine, both drug and non-drug related, was seen in 15/46 pts (33%), but treatment was discontinued in only 3 patients due to a renal adverse event. Acute renal failure was documented in 4 pts (9%), 2 (4%) of whom also had possible tumor lysis. 78% of pts had Grade 1 or 2 peripheral neuropathy (PN) at baseline. Exacerbation of PN was rare, and there were no study discontinuations or dose reductions due to PN. Conclusions: In the context of this heavily pre-treated MM population, single agent CFZ was able to induce CBR in 26% of MM patients, the majority of whom had failed BTZ, LEN, THAL, and SCT. CFZ was generally well-tolerated, and toxicities were manageable. Importantly, exacerbation of pre-existing PN was rare and did not result in dose reduction or discontinuation of therapy. These observations support further evaluation of CFZ as a promising new agent in MM. Enrollment is proceeding at an escalated dose (based on tolerability) in this trial. Additional studies of CFZ in patients who are less heavily pretreated and in combination with other chemotherapy agents are ongoing.

Effect of lenalidomide (LEN) on biochemical responses and clinical benefit (CB) as a single agent in chemotherapy-naive castration-resistant prostate cancer (CRPC).

2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 128-128 ◽  
Author(s):  
Chadi Nabhan ◽  
Anand Patel ◽  
Dana Villines ◽  
Kathy Tolzien ◽  
Susan K. Kelby ◽  
...  
Keyword(s):  
Adverse Events ◽  
Clinical Benefit ◽  
Single Agent ◽  
Complete Response ◽  
Median Number ◽  
Castration Resistant Prostate Cancer ◽  
Serious Adverse Events ◽  
Biochemical Responses ◽  
Grade 3 ◽  
Dose Reductions

128 Background: LEN has anti-angiogenesis and immunomodulatory properties making it ideal to investigate in CRPC. We report on a phase II study investigating LEN in chemotherapy-naïve CRPC patients (pts) Methods: Eligible pts received LEN at 25 mg daily on days 1 – 21 every 28-days until progression. Daily aspirin or coumadin were required. Responses were assessed every 2 cycles. Toxicity was assessed every cycle. Primary end point: The CB of LEN [Sum of complete response (CR), partial response (PR) and stable disease (SD)]. Secondary end points: Toxicity, time to radiographic and PSA progression (TTP and TTP-PSA), time to next treatment (TTNT), overall survival (OS), and LEN’s impact on quality of life (QOL). Results: 31 pts were enrolled; 27 response-evaluable (1 withdrew consent, 3 off per choice after adverse events). Median age is 74 (range 58-89) with 24 (77%) having Gleason ≥ 7 disease. Median PSA is 66 (2.1-918.6). Six pts (19%) had liver/lung involvement. Fourteen pts (51%) showed biochemical response with 4 (15%) having >50% PSA drop. TTP-PSA is 4 months (2-11). No radiographic responses seen but 17 pts had SD for a median of 4 months (2-16) (CB=55%). Median number of LEN cycles was 3 (2-15). With a median follow-up of 18 months (5-38), 17 patients (55%) remain alive; median OS of 18 months. Grade 3/4 hematologic toxicities were most common (neutropenia 41%, leukopenia 12%, anemia 9%, thrombocytopenia 9%). Other grade 3/4 toxicities: venothromboembolism, atrial fibrillation, and dehydration (6% each). Serious adverse events (SAEs) were witnessed in 10 pts (32%) with only 1 (3%, rash) definitely related to LEN. Others were not related or possibly related. Of 27 pts, 7 (26%) had a dose reduction and 2 (7%) required two dose reductions. Dose reductions occurred after cycle 3. QOL scales suggested no adverse impact. Median TTNT is 2 months (9 pts received chemotherapy, 10 pts went onto studies, 3 pts received hormonal therapies, 4 pts received radiation, 3 pts had no therapy yet, and 2 pts remain on LEN). Conclusions: LEN is active as monotherapy in CRPC. Biochemical responses are witnessed and clinical benefit is observed. Myelosuppression is the most common toxicity.

Sign in / Sign up

Export Citation Format

Share Document