A retrospective study of efficacy and safety of mechlorethamine, vindesine, liposomal doxorubicin, and prednisone (MODP) in relapsed/refractory classical Hodgkin lymphoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e19516-e19516
Author(s):  
Min-Hang Zhou ◽  
Chunmeng Wang ◽  
Yang Liu ◽  
Wenjing Ku ◽  
Qingming Yang ◽  
...  
Keyword(s):  
Retrospective Study ◽  
Liposomal Doxorubicin ◽  
Checkpoint Inhibitors ◽  
Progression Free Survival ◽  
Response Assessment ◽  
Brentuximab Vedotin ◽  
Combination Regimen ◽  
Salvage Regimen ◽  
Heavily Pretreated ◽  
Grade 3

e19516 Background: There are few optimized therapeutic options for relapsed and/or refractory classic Hodgkin’s lymphoma (r/rCHL), especially in patients who failed in treatments of autologous stem cell transplantation (ASCT), brentuximab vedotin or even immune checkpoint blockage. Therefore, we developed a chemotherapeutic scheme to evaluate the efficacy in r/rCHL patients with previous various lines of therapies. Methods: Between January, 2014 and December, 2019, a retrospective study was performed on r/rCHL patients from Chinese PLA general hospital who were treated with MOAP regimen consisting of mechlorethamine 6mg/m2, vindesine 4mg, liposomal doxorubicin 15mg/m2 on days 1 and 8, prednisone 1mg/kg per day on days 1 to 10 (MOAP) every 4 weeks. CT or PET/CT were done every two cycles to assess the response. Patients treated with MOAP regimen and complete clinical data were included. Patients with less than two cycles of MOAT or unavailable response assessment were excluded. The primary endpoint were complete remission (CR) and progression-free survival (PFS). Results: A total of 87 patients were included and five patients were excluded, so 82 patients were eligible in the study. The median previous lines and cycles of chemotherapy was 2 (range, 1-7), and 9 (range, 3-31), respectively. All the eligible patients received MOAP regimen for a median 4 cycles (range from 2 to 8), and overall response rate (ORR) was 87.8% including 40 patients in CR (48.8%) and 32 in PR (39.0%). In patients with ≥ 3 lines or ≥ 10 cycles of chemotherapy, up to 50.0% and 41.0% of patients achieved CR, respectively. In patients with previous ASCT, 31.6% of patients also achieved CR. Patients with previous checkpoint inhibitors had even higher CR than those without checkpoint inhibitors, though not significantly (51.6% vs. 47.1%, p = 0.689). Median PFS in patients with CR, PR and SD/PD were 43.8 months, 9.6 months and 6.1 months, respectively (p = 0.000).Patients with < 3 previous lines of chemotherapy had a favorable PFS than those with ≥ 3 previous lines (not reached vs. 14.4 months, (p = 0.032). No differences in PFS were observed in terms of previous cycles of chemotherapy, ASCT and checkpoint inhibitors. Grade ≥ 3 adverse events included 37 leukopenia (45.1%), 16 lung infection (19.5%), 11 anemia (13.4%), 4 thrombocytopenia (4.9%), 3 febrile neutropenia (3.7%) and 3 increased transaminase (3.7%). Conclusions: The MOAP combination regimen produced a favorable CR in r/rCHL failing or progressing on ASCT, checkpoint inhibitors, multiple cycles or lines of chemotherapies. It is an effective salvage regimen in heavily pretreated r/r CHL.

A phase Ib study of napabucasin plus weekly paclitaxel in patients with advanced melanoma.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 9553-9553
Author(s):  
William Jeffery Edenfield ◽  
Carlos Becerra ◽  
Fadi S. Braiteh ◽  
Alexander I. Spira ◽  
Ryan J. Sullivan ◽  
...  
Keyword(s):  
Checkpoint Inhibitors ◽  
Braf Inhibitor ◽  
Progression Free Survival ◽  
Advanced Melanoma ◽  
Braf V600e ◽  
Weekly Paclitaxel ◽  
Combination Regimen ◽  
Clinical Safety ◽  
Grade 3 ◽  
Anti Tumor Activity

9553 Background: Napabucasin is a first-in-class cancer stemness inhibitor, identified by its ability to inhibit STAT3-driven gene transcription and spherogenesis of cancer stem cells (Li et al PNAS 112 (6):1839, 2015). Synergistic anti-tumor activity with paclitaxel was observed in pre-clinical testing, and a favorable clinical safety profile was established in a phase I/II trial in patients (pts) with advanced solid tumors. A phase 1b trial was established to evaluate the safety and preliminary signs of anti-cancer activity of the combination regimen in pts with advanced melanoma. Methods: Pts with melanoma were enrolled after failure of standard therapies for advanced disease. Napabucasin 480 or 500 mg orally twice daily was administered with paclitaxel 80 mg/m2 IV weekly for 3 of every 4 weeks. Adverse events were evaluated using CTCAE v4.03 and objective tumor assessments were obtained every 8 weeks and evaluated per RECIST 1.1 criteria. Results: A total of 12 pts with advanced melanoma were enrolled after a median 3 prior lines of therapy (including immune checkpoint inhibitors, BRAF-inhibitor if presence of BRAF V600E mutation). Protocol therapy was well tolerated with grade 3 AEs including diarrhea (n = 3), abdominal pain (n = 1), and fatigue (n = 1). Partial response (PR) was observed in 1 pt. Stable disease of at least 24 weeks or more was achieved by 33% of patients (n = 4) and the median progression-free survival (mPFS) was 3.7 months. Prolonged survival of 1 year or more was achieved by 33% of pts (n = 4), with a median overall survival (mOS) of 10.4 months. Conclusions: Napabucasin plus weekly paclitaxel has shown clinical safety and encouraging anti-tumor activity in a cohort of pts with previously treated advanced melanoma. The RP2D in combination with weekly paclitaxel was established to 480 mg orally bid. The data suggest that targeting stemness pathways with napabucasin may be a novel therapeutic strategy for melanoma. Clinical trial information: NCT01325441.

Bortezomib in Combination with Pegylated Liposomal Doxorubicin and Thalidomide (VDT) for the Treatment of Previously Untreated Multiple Myeloma.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3614-3614 ◽  
Author(s):  
Asher A. Chanan-Khan ◽  
Kena C. Miller ◽  
Dawn DePaolo ◽  
Swaminathan Padmanabhan ◽  
Amy Whitworth ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Venous Thromboembolism ◽  
Clinical Efficacy ◽  
Liposomal Doxorubicin ◽  
Pegylated Liposomal Doxorubicin ◽  
Response Assessment ◽  
Hematologic Toxicity ◽  
Heavily Pretreated ◽  
Grade 3 ◽  
Beta 2 Microglobulin

Abstract Introduction: Orlowski et al were the first to report that addition of PLD resulted in enhanced efficacy of bortezomib. To further optimize the clinical efficacy of these agents we included thalidomide to the regimen. In a previous report we described the clinical efficacy of this novel, non-steroidal regimen that incorporated bortezomib (V), pegylated liposomal doxorubicin (D) and thalidomide (T) in patients with relapsed or refractory multiple myeloma (MM). High clinical responses in heavily pretreated patients, even in the absence of steroids encouraged us to investigate this regimen in previously untreated MM patients. Here we report for the first time the efficacy and toxicity profile of the VDT regimen in treatment naïve MM patients enrolled on a phase II clinical study at our center. METHOD: All previously untreated MM patients were eligible for this study. Bortezomib (1.3mg/m2) was given on days 1, 4, 15, and 18, pegylated liposomal doxorubicin was given (20mg/m2) on days 1 and 15 and thalidomide (200mg) was given everyday continuously throughout the treatment. Patients received treatment on a 4-week cycle. Acyclovir 400mg PO BID and low-dose warfarin was given for prophylaxis of herpes zoster and venous thromboembolism respectively. RESULTS: A total of 26 patients (median age-- 60 range 40–82 years), 16 M and 10 F have so far been enrolled. Advance stage III disease was noted in ---of the patients. The median beta 2 microglobulin was 4 (range1.6–9.7), albumin of 4 (range 3.1–4.8) and LDH was 333 (range 152–1057). Patients received a median of 5 treatment cycles (range 1–8). Toxicity: The most common grade 3 or 4 hematologic toxicities included lymphopenia (27%) and neutropenia (15%), while the non-hematologic toxicity included infections 15% (n=4 patients). The incidence of grade 3 or 4 plantar palmar erythrodysthesia was 4% (n=1). Venous thromboembolism was not observed in any patient to date. Response: To date 17 patients are available for response assessment (EBMT criteria?), 7 patients are too early for response assessment. The ORR of this regimen is 65% with IFE negative CR observed in 3 patients (17.6%). Another 5 patients achieved a stable disease with only 1 progressive disease observed on the regimen so far. Conclusion: VDT is a novel non-steroidal regimen with clinical efficacy in previously untreated myeloma patients. Overall toxicity is manageable. Several patients remain on treatment and currently not evaluable for response. Detailed and updated results of this study will be presented at the meeting.

scholarly journals Pomalidomide-Dexamethasone in the Management of Heavily Pretreated Multiple Myeloma

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 1-1
Author(s):  
Claudio Cerchione ◽  
Lucio Catalano ◽  
Davide Nappi ◽  
Anna Emanuele Pareto ◽  
Gerardo Musuraca ◽  
...  
Keyword(s):  
Oral Administration ◽  
Oral Treatment ◽  
Novel Agents ◽  
Hematologic Toxicity ◽  
Salvage Regimen ◽  
Good Compliance ◽  
Impressive Result ◽  
Heavily Pretreated ◽  
Pretreated Patients ◽  
Grade 3

Background Pomalidomide is a new generation IMID, with a very good compliance, thanks to oral administration, which can be used also in heavily pretreated patients, in a domestic setting. Aims In this retrospective observational trial, It has been evaluated efficacy and tolerance of pomalidomide plus dexamethasone (PD) as salvage regimen in heavily pretreated patients with relapsed and refractory MM (rrMM), whose prognosis is particularly severe. Methods 57 patients (31 M/26 F), with rrMM, median age at diagnosis 69 years (r. 52-86), and median age at start of treatment 76 years (r.56-90) treated with several lines of treatments (median 7, r. 2-11), every refractory to all the drugs previously received (also Bortezomib, Thalidomide and Lenalidomide), received Pomalidomide-Dexamethasone (Pomalidomide 4 mg for 21 days, Dexamethasone 40 mg days 1,8,15,22, pegfilgrastim day +8) every 28 days, until progression. ISS was equally distributed, and cytogenetic at relapse was evaluable in 14 patients. All the patients had previously been treated with schedule containing bortezomib and IMIDs. 63% (36/57) had undergone at least to a single ASCT. All patients were relapsed and refractory to last therapies received before PD. Results Pomalidomide was well tolerated, with grade 3-4 transfusion-dependent anemia in 58% (33/57) of patients, 44% (23/57) grade 3-4 neutropenia (pegfilgrastim in primary prophylaxis was given, no hospitalization was required, no septic shocks were observed), 40% (23/57) grade 3-4 thrombocytopenia without hemorrhagic events and transfusion-dependence. No severe extra-hematologic toxicity was observed. According to IMWG, ORR1 (≥PR) was 47.3% (27/57: 5 CR, 11 VGPR, 7 PR, 4 MR), but, considering that we are evaluating a cohort of heavily pretreated patients, with poor prognosis, another parameter should be considered, ORR2 (≥SD), considering stable disease as a successful result in progressive MM. ORR2 was 77.1% (17 SD). These can be considered as impressive result in this subset of patients. Oral treatment gives a really good compliance, in frail and unfit patients, and response, when present, is always really fast (median time to response: 2 months (r.1-6)), median OS from diagnosis was 94 months (range 21-234), median OS from start of pomalidomide was 9 months (range 1-25). Nine patients have surprisingly achieved a notable response (3 VGPR, 4 PR, 2 MR) after failure of novel agents (i.e. Carfilzomib, Daratumumab and Pomalidomide). Conclusions Pomalidomide-dexamethasone has shown significant efficacy and a very good compliance, thanks to oral administration, in a particularly severe setting of heavily pretreated patients, relapsed and refractory to all available therapeutic resources, also after failure of novel agents. Disclosures Lucchesi: Novartis: Honoraria; Pfizer: Honoraria; Incyte: Honoraria.

Efficacy and safety of weekly paclitaxel in elderly patients with heavily pretreated platinum-resistant ovarian carcinoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e17552-e17552
Author(s):  
Rodrigo Sanchez-Bayona ◽  
Pablo Tolosa ◽  
Ana Sanchez de Torre ◽  
Alicia Castelo ◽  
Elsa Bernal-Hertfelder ◽  
...  
Keyword(s):  
Peripheral Neuropathy ◽  
Ovarian Carcinoma ◽  
Progression Free Survival ◽  
High Grade ◽  
Efficacy And Safety ◽  
Free Survival ◽  
Serous Ovarian Carcinoma ◽  
Platinum Resistant ◽  
Heavily Pretreated ◽  
Grade 3

e17552 Background: In platinum-resistant ovarian cancer treatment, single-agent paclitaxel can be used alone or in combination with bevacizumab. We aimed to assess the efficacy and safety profile of a weekly paclitaxel (WP) scheme in heavily pretreated platinum-resistant high-grade serous ovarian carcinoma. Methods: We retrospectively analyzed 30 adult patients with platinum-resistant high-grade serous ovarian carcinoma treated with WP at our institution between 2015 and 2020. Patients with platinum-resistant ovarian, fallopian tube or primary carcinoma of the peritoneum who had received at least 3 doses of WP (80 mg/m2) alone or in combination with bevacizumab until disease progression or unacceptable toxicity were included in the analysis. Progression-free survival was assessed according to the Response Evaluation Criteria in Solid Tumors version 1.1. Information about toxicity was gathered from medical reports and lab tests. Kaplan-Meier curves and Log-rank test were performed for survival estimates. Results: In our sample, the median age was 68 years (IQR: 60-75) and the median number of previous lines of systemic treatment was 3 (range 1-5). 40% of patients received WP in combination with bevacizumab. The disease control rate was 60.7% (42.9% partial response and 17.8% stable disease). In the overall analysis, the median progression-free survival (mPFS) was 5.0 months (95% CI: 2.0-7.1 months). The presence of ascites significantly shortened the mPFS compared to patients without it (1.1 vs 5.1 months, p < 0.001). Even though the addition of bevacizumab to WP improved the mPFS, the difference was not statistically significant compared to WP alone (7.1 vs 4.06 months, p=0.30). Peripheral neuropathy was the most common adverse event (78% all grades, 18% grade 3). No grade 3 hematologic toxicity was registered. Treatment was discontinued in 6 patients (20%) – 4 due to peripheral neuropathy and two because of toxicoderma. Conclusions: In our sample, WP was an active and safe regimen in heavily pretreated platinum-resistant ovarian carcinoma. WP was well tolerated in elderly patients. The presence of ascites was associated to a shorter PFS in patients treated with WP compared to ascites-free patients.

scholarly journals Ramucirumab in Combination with Pembrolizumab in Treatment-Naïve Advanced Gastric or GEJ Adenocarcinoma: Safety and Antitumor Activity from the Phase 1a/b JVDF Trial

Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2985
Author(s):  
Ian Chau ◽  
Nicolas Penel ◽  
Andres O. Soriano ◽  
Hendrik-Tobias Arkenau ◽  
Jennifer Cultrera ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Checkpoint Inhibitors ◽  
Objective Response ◽  
Progression Free Survival ◽  
Clinical Activity ◽  
Metastatic Setting ◽  
Duration Of Response ◽  
Treatment Naïve ◽  
Combined Positive Score ◽  
Grade 3

Ramucirumab (anti-VEGFR2) plus pembrolizumab (anti-PD1) demonstrated promising antitumor activity and tolerability among patients with previously treated advanced cancers, supporting growing evidence that combination therapies modulating the tumor microenvironment may expand the spectrum of patients who respond to checkpoint inhibitors. Here we present the results of this combination in first-line patients with metastatic G/GEJ cancer. Twenty-eight patients (≥18 years) with no prior systemic chemotherapy in the advanced/metastatic setting received ramucirumab (8 mg/kg days 1 and 8) plus pembrolizumab (200 mg day 1) every 3 weeks as part of JVDF phase 1a/b study. The primary endpoint was safety. Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), and overall survival (OS). Tumors were PD-L1-positive (combined positive score ≥ 1) in 19 and -negative in 6 patients. Eighteen patients experienced grade 3 treatment-related adverse events, most commonly hypertension (14%) and elevated alanine/aspartate aminotransferase (11% each), with no grade 4 or 5 reported. The ORR was 25% (PD-L1-positive, 32%; PD-L1-negative, 17%) with duration of response not reached. PFS was 5.6 months (PD-L1-positive, 8.6 months; PD-L1-negative, 4.3 months), and OS 14.6 months (PD-L1-positive, 17.3 months; PD-L1-negative, 11.3 months). Acknowledging study design limitations, ramucirumab plus pembrolizumab had encouraging durable clinical activity with no unexpected toxicities in treatment-naïve biomarker-unselected metastatic G/GEJ cancer, and improved outcomes in patients with PD-L1-positive tumors.

scholarly journals Melflufen and Dexamethasone in Heavily Pretreated Relapsed and Refractory Multiple Myeloma

2020 ◽  
pp. JCO.20.02259
Author(s):  
Paul G. Richardson ◽  
Albert Oriol ◽  
Alessandra Larocca ◽  
Joan Bladé ◽  
Michele Cavo ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Overall Response Rate ◽  
Response Rate ◽  
Progression Free Survival ◽  
Free Survival ◽  
Duration Of Response ◽  
Heavily Pretreated ◽  
Grade 3

PURPOSE Melphalan flufenamide (melflufen) is a first-in-class peptide-drug conjugate that targets aminopeptidases and rapidly and selectively releases alkylating agents into tumor cells. The phase II HORIZON trial evaluated the efficacy of melflufen plus dexamethasone in relapsed and refractory multiple myeloma (RRMM), a population with an important unmet medical need. PATIENTS AND METHODS Patients with RRMM refractory to pomalidomide and/or an anti-CD38 monoclonal antibody received melflufen 40 mg intravenously on day 1 of each 28-day cycle plus once weekly oral dexamethasone at a dose of 40 mg (20 mg in patients older than 75 years). The primary end point was overall response rate (partial response or better) assessed by the investigator and confirmed by independent review. Secondary end points included duration of response, progression-free survival, overall survival, and safety. The primary analysis is complete with long-term follow-up ongoing. RESULTS Of 157 patients (median age 65 years; median five prior lines of therapy) enrolled and treated, 119 patients (76%) had triple-class–refractory disease, 55 (35%) had extramedullary disease, and 92 (59%) were refractory to previous alkylator therapy. The overall response rate was 29% in the all-treated population, with 26% in the triple-class–refractory population. In the all-treated population, median duration of response was 5.5 months, median progression-free survival was 4.2 months, and median overall survival was 11.6 months at a median follow-up of 14 months. Grade ≥ 3 treatment-emergent adverse events occurred in 96% of patients, most commonly neutropenia (79%), thrombocytopenia (76%), and anemia (43%). Pneumonia (10%) was the most common grade 3/4 nonhematologic event. Thrombocytopenia and bleeding (both grade 3/4 but fully reversible) occurred concomitantly in four patients. GI events, reported in 97 patients (62%), were predominantly grade 1/2 (93%); none were grade 4. CONCLUSION Melflufen plus dexamethasone showed clinically meaningful efficacy and a manageable safety profile in patients with heavily pretreated RRMM, including those with triple-class–refractory and extramedullary disease.

scholarly journals ATIM-20. A RETROSPECTIVE STUDY EVALUATING THE SAFETY AND SURVIVAL OF THE COMBINATION OF PD-1 IMMUNE CHECKPOINT BLOCKADE AND BEVACIZUMAB IN RECURRENT GLIOBLASTOMA

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi5-vi5
Author(s):  
Joshua Friedman ◽  
Adilia Hormigo
Keyword(s):  
Retrospective Study ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Recurrent Disease ◽  
Checkpoint Inhibitors ◽  
Immune Surveillance ◽  
Immune Checkpoint Blockade ◽  
Recurrent Glioblastoma ◽  
Grade 3 ◽  
Recurrent Gbm

Abstract INTRODUCTION Immune checkpoint inhibitors (ICI) have demonstrated clinical efficacy in a variety of cancers. It is known that cancer including glioblastoma (GBM) induces an immunosuppression. Bevacizumab by normalizing blood vessels in the tumor can facilitate immune surveillance and potentially improve the efficacy of ICI in GBM patients. We analyze GBM patients with recurrent disease treated with ICI and bevacizumab. METHODS We retrospectively review records of patients diagnosed with recurrent GBM treated at our institution with Pembrolizumab or Nivolumab and bevacizumab and evaluate for tolerance and outcomes. RESULTS Twenty-one patients, 12 men and 9 women with median age 62 (range 36–78) and KPS 70 (range 60–90) were treated with a median of 10 ICI cycles (range 4–29) and 5 of bevacizumab (range 0–21). A total of 8 patients (38%) had immune-related adverse events (IRAE): 3 grade 1, 3 grade 2 and 2 grade 3. A patient with pneumonitis required cessation of ICI. Median OS for the 21 patients was 22 months (range 6–41). The 7 patients that had MGMT detected in their tumors had a median OS of 27 months (range 23–41) compared to a survival of 21 months (range 6–24) for the 13 patients that had MGMT undetected. One had undetermined MGMT and her OS was 21 months. The median survival for all the patients from onset of ICI was 10 months (range 1–25) and 10 of them (47.6%) survived > 12 months. DISCUSSION The development of IRAE was common but self-limiting, allowing continuation of the treatment in all but one patient. The combination of ICI and bevacizumab increased survival. Our data needs to be interpreted with caution, as it is a retrospective analysis of a small group of patients. However, these results warrant prospective studies using the combination of ICI and bevacizumab to treat recurrent GBM.

A Phase II Trial of Doxil, Vincristine and Reduced Schedule Dexamethasone (DVd) for Patients with Relapsed or Refractory Multiple Myeloma.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2415-2415 ◽  
Author(s):  
Paul Masci ◽  
Mary A. Karam ◽  
Luba Platt ◽  
Steven Andresen ◽  
Alan Lichtin ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Phase Ii ◽  
Liposomal Doxorubicin ◽  
Phase Ii Trial ◽  
Pegylated Liposomal Doxorubicin ◽  
Progression Free Survival ◽  
Response Rates ◽  
Free Survival ◽  
Median Progression Free Survival ◽  
Grade 3

Abstract Patients with newly diagnosed multiple myeloma (MM) typically have responses to initial cytotoxic or steroid based therapy. Disease relapse occurs in all patients. As high as 90% of patients with relapsed or refractory disease will have over-expression of the multi-drug resistance (MDR) gene. Pharmacokinetic data suggest that prolonged exposure to high concentrations of doxorubicin can overcome MDR. Pegylated liposomal doxorubicin can theoretically achieve this goal as the angiogenic activity of the MM bone marrow is significantly increased. We proceeded with a phase II trial to evaluate the response rate of patients with relapsed or refractory MM (R/R-MM) to the DVd regimen. Eligible patients had clinically active R/R-MM following at least one prior cytotoxic based treatment regimen. Patients received intravenous (IV) pegylated liposomal doxorubicin 40 mg/m2 day 1, vincristine 2 mg day 1 and oral or IV dexamethasone 40 mg daily days 1–4. Cycles were repeated every 28 days for a minimum of 6 cycles and 2 cycles after best response. Myeloma parameters were measured at the start of each cycle. SWOG criteria were used to determine response. Thirty-five patients (21 male and 14 female) with R/R-MM clinically active disease were enrolled. Median age was 59 years (range 43–87). Patients received a median of 2 (range 1–4) prior cytotoxic based treatments. All patients received at least one cycle of treatment (median=5; range 1–12) and were evaluable for response. Ten (29%) patients responded to therapy; 5 partial responses (PR &gt; 50%) and 5 responses (R &gt; 75%) were observed after a median of 2 cycles (range 1–9). Median progression free survival of responding patients (PR + R) was 4.5 mos. (range 0.67–44.8). Patients achieving R had a median progression free survival of 32.5 mos. (3.0–44.8). Thirteen (37%) patients had stable disease (SD) for a median of 1.4 mos. (range 0.8–9.9). Twelve (34%) patients had progressive disease after a median of 1 cycle (range 1–5). The most common toxicities were hematologic; there were four occurrences of febrile neutropenia. Three patients experienced grade 3 constipation and one grade 3 palmar-plantar erythrodysethesia was observed. This study suggests that in patients with R/R-MM, DVd alone yields response rates similar to bortezomib with patients achieving an R experiencing a durable plateau phase. Ongoing studies of DVd in combination with thalidomide or CC-5013 in patients with R/R-MM have resulted in higher and better quality response rates (comparable to autologous SCT) translating to a durable progression free survival. We would not recommend the DVd regimen in patients with R/R-MM without the addition of an immune modulator such as thalidomide.

An Open-Label Study of Pegylated Liposomal Doxorubicin, Vincristine and Reduced-Dose Dexamethasone Combination Therapy in Newly Diagnosed Multiple Myeloma Patients in Chinese Population.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4816-4816
Author(s):  
Yang Shen ◽  
Zhixiang Shen ◽  
Bin Jiang ◽  
Jian Hou ◽  
Rong Zhan ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Chinese Population ◽  
Liposomal Doxorubicin ◽  
Pegylated Liposomal Doxorubicin ◽  
Progression Free Survival ◽  
Combination Regimen ◽  
Newly Diagnosed ◽  
Open Label ◽  
Open Label Study ◽  
Reduced Dose

Abstract BACKGROUND: Pegylated liposomal doxorubicin (CAELYX®) is a liposomal formulation of doxorubicin sterically stabilized by the grafting of segments of polyethylene glycol (PEG) onto the liposomal surface. Given the demonstrated efficacy of VAD (vincristine and doxorubicin and oral dexamethasone) in Multiple Myeloma (MM) patients and the potential for CAELYX® to extend the duration of bone marrow exposure to therapeutic levels of doxorubicin, a combination regimen of CAELYX®, vincristine, and reduced-dose dexamethasone (DVD) has been actively investigated in MM patients. Studies showed that substituting CAELYX® for doxorubicin in the VAD regimen and reducing the dose of dexamethasone in MM patients improves the safety profile and convenience of the treatment regimen without compromising efficacy. Due to potential differences in metabolism of these patients, safety and efficacy results may vary. Thus, we carried out this study in 82 newly diagnosed MM patients in China, in order to demonstrate the efficacy and safety profiles of DVD. METHODS: Patients (n=82) from 15 sites were recruited in this study. CAELYX® (40mg/m2) was infused intravenously over 60-minutes, administered every 28 days. Vincristine (2.0mg) was administered intravenously on Day 1 of each cycle. Dexamethasone (40 mg) was administered from Day 1- Day 4 of each cycle orally or intravenously. The treatment was repeated every 28 days for 4 cycles. RESULTS: Upon ITT analysis, the overall response rate was approximately 68% (56/82); 11% of the patients achieved complete remission (CR), 40% achieved partial response (PR), 17% achieved minimal response; 15% had stable disease (SD), and 12% o had progressive disease (PD) after the treatment. The cumulative 4-month progression-free survival (PFS) was 88%. The incidence of all the adverse events was 46%. The most common non-hematological toxicities were palmar-plantar erythrodysesthesia (13.4%) and stomatitis (6.1%), respectively. CONCLUSION: Pegylated liposomal doxorubicin, vincristine and reduced dose dexamethasone combination (DVD) regimen is an effective and safe regimen in newly diagnosed multiple myeloma patients in Chinese population.

Lenalidomide with Low or Intermediate Dose Dexamethasone in Patients with Relapsed or Refractory Myeloma

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4028-4028 ◽  
Author(s):  
Meletios A Dimopoulos ◽  
Maria Roussou ◽  
Maria Gavriatopoulou ◽  
Magdalini Migkou ◽  
Maria Gkotzamanidou ◽  
...  
Keyword(s):  
Low Dose ◽  
Progression Free Survival ◽  
Similar Frequency ◽  
Significant Efficacy ◽  
Heavily Pretreated ◽  
Mdrd Formula ◽  
Receive Treatment ◽  
Grade 3 ◽  
Line Of Therapy ◽  
Intermediate Dose

Abstract Abstract 4028 Lenalidomide is an immunomodulatory drug with significant efficacy in relapsed and refractory multiple myeloma (MM) in combination with high or intermediate dose dexamethasone (RD). Previous studies in newly diagnosed patients (pts) showed that the combination of lenalidomide plus low dose dexamethasone (Rd) is associated with better overall survival (OS) and lower toxicity. However, there are no data comparing different dose of dexamethasone with lenalidomide in pts with relapsed or refractory myeloma. To address this issue we analyzed, retrospectively, 102 consecutive pts with relapsed or refractory MM, treated in a single center (Department of Clinical Therapeutics, University of Athens, Greece), who received lenalidomide with dexamethasone: 70 patients received lenalidomide and dexamethasone at a dose 40 mg PO, on days 1–4 and 15–18 for the first 4 cycles and only on days 1–4 thereafter (intermediate dose; group RD) and 32 pts who received lenalidomide and low dose dexamethasone (40 mg PO weekly; group Rd). Lenalidomide was administered on days 1–21 according to creatinine clearance (CrCl): 25mg/day for CrCl >50 ml/min, 10 mg/day for CrCl 30–50 ml/min, 15 mg every other day for CrCl 15–29 ml/min and for pts on dialysis 5 mg, once daily. RD and Rd were repeated every 28 days till disease progression or unacceptable toxicity. All pts received DVT prophylaxis with aspirin 100 mg/day except 18 pts (18%) who were already on coumadin or LMWH for other indications (atrial fibrillation, previous DVT, etc). The median age of the pts was 67 years for RD and 69 years for Rd (p=0.36). There were no significant differences regarding the presence of specific cytogenetic abnormalities or high risk cytogenetics (p>0.3 for all comparisons). Patients in group RD were more heavily pretreated and had more often exposed to thalidomide (69% vs. 43%, p=0.013) or bortezomib (76% vs. 63%, p=0.1) and had more often thalidomide resistance (43% vs. 10%, p=0.001) or bortezomib resistance (46% vs. 20%, p=0.014). The number of prior therapies in group RD was 2 (range: 1–6) vs. 1 (range: 1–3) in group Rd (p=0.007), while 60% in RD vs. 30% in Rd were refractory to last line of therapy (p=0.006). Pts in RD have received a median of 10 cycles (range: 1–44 cycles) and only 2 pts are still receiving therapy, while pts in Rd have received a median of 5 (range: 1–17) cycles but 21 (70%) continue to receive treatment. The median follow-up was 18 months (range: 1–58 months) for RD and 7.6 months (range: 1.9–23.6 months) for Rd. Responses, according to IMWG criteria, were not different among the two groups: in RD, CR (26%), PR (36%), SD (26%), PD (12%) and in Rd, CR (13%), PR (53%), SD (27%) and PD (7%). At least PR was observed in 32% of pts in RD and in 66% in Rd (p=0.45) of thalidomide-refractory pts, and in 45% in RD and 33% in group Rd (p=0.72) of bortezomib-refractory pts. The median progression-free survival (PFS) was 10 months (range: 1–55 months) for RD and has not been reached for Rd, but the 6-month PFS rate was 84% (p=0.003). The median time to next treatment was 11 months (range: 0.9–53 months) for RD and has not been reached for Rd. The OS was 18 months (range: 0.9–58 months) for RD and has not been reached for Rd, but the 1-year probability for OS was 81% (p=0.27). After adjustment for prior thalidomide and/or bortezomib resistance, disease refractory to last line of therapy and number of prior therapies, there was no difference for RD vs. Rd for OS (HR: 1.7, 95% CI 0.572–5, p=0.338) but Rd was associated with better PFS than RD (HR: 0.36, 95% CI 0.14–0.95, p=0.038). We also evaluated the effect of treatment on renal impairment reversal. Twenty nine pts (40%) in group RD and 7 pts (23%) in group Rd had an eGFR, calculated by the MDRD formula, of <60 ml/min. Seven patients (25%) from group RD and none from group Rd achieved renal response (p=0.199), according to the IMWG criteria. More patients treated with RD developed grade ≥3 neutropenia (23% vs. 3%) and fatigue ≥grade 3 (15% vs. 3%); 3 pts from group RD developed thrombosis (2 patients DVT and one pulmonary embolism) vs. none with Rd. Other toxicities occurred with similar frequency between RD and Rd. This is the first analysis, which compared the role of intermediate and low dose dexamethasone with lenalidomide in pts with relapsed or refractory myeloma. Our data indicate that Rd is probably as effective as RD, while it may be better tolerated. Updated results regarding OS and PFS as well as renal recovery will be presented at the meeting. Disclosures: Dimopoulos: Celgene: Honoraria. Terpos:Celgene: Honoraria.

Sign in / Sign up

Export Citation Format

Share Document