Clinical Results in Patients with Primary and Secondary Myelofibrosis Treated with Monthly Cycles of Oral Melphalan.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4985-4985
Author(s):  
Ida Carmosino ◽  
Roberto Latagliata ◽  
Massimo Breccia ◽  
Laura Cannella ◽  
Federico Vozella ◽  
...  
Keyword(s):  
Response Rate ◽  
Conflicts Of Interest ◽  
Previous History ◽  
Clinical Results ◽  
Median Number ◽  
Hematological Toxicity ◽  
Costal Margin ◽  
Best Response ◽  
Number Of Treatment ◽  
Spleen Enlargement

Abstract Abstract 4985 Prolonged continuous oral Melphalan treatment was successfully employed in patients with Idiopathic Myelofibrosis (IM); however, a high incidence of evolution into blastic phase (BP) was observed. In order to reduce the incidence of BP and other side effects, a different Melphalan schedule with intermittent monthly cycles was tested at our Institution. From 1/2003 to 2/2009, 24 patients (16 males and 8 females, median age 66.2 years, range 41.7 – 76.2) were enrolled into the study; 19/24 had primary IM while in 5 there was a previous history of Polycythemia Vera/Essential Thrombocythemia. Six patients (25%) had been pretreated with Hydroxyurea. A symptomatic splenomegaly was present in all patients, with median spleen enlargement below costal margin of 12 cm (range 7 – 22). Median WBC level was 11.6 × 109/l (range 3.6 – 63.6), with 11/24 patients having WBC > 12.0 × 109/l; in addition, 3 patients had PLT level > 500 × 109/l, 11 patients Hb level < 10 g/dl and 3 patients had transfusional requirement. Melphalan was administered orally at the dose of 8 mg/day for 5 consecutive days every month. Twelve patients (50%) had a reduction of spleen enlargement > 75%, 2 patients > 50% and 1 patient > 25%, with a global response rate of 15/24 patients (62.5%): the remaining 9 patients had no variation in spleen volume. Elevated WBC values reduced to normal in all but one patient, elevated PLT values reduced to normal in 2 out of 3 patients, transfusional requirement disappeared in 1 out of 3 patients. Median number of cycles to best response was 10 (range 2 – 30). As concerns hematological toxicity, 4 patients had Hb decrease < 8 g/dl, with 3/4 requiring transient transfusional support, and 1 patient had PLT decrease to < 50 × 109/l. One patient resistant to treatment died from broncopneumonia and 1 patient with normal PLT values died from cerebral hemorrhage; two patients had a grade 3 – 4 gastro-intestinal hemorrhage. Interestingly, only 2/24 patients (8.3%) had a BP evolution after 8 and 16 months from start of Melphalan, respectively. After a median number of treatment cycles of 18 (range 2 – 68), 12 patients are still in therapy and 12 discontinued Melphalan due to toxicity (4), resistance (3), relapse (3) or evolution to BP (2). In conclusion, the intermittent cyclic schedule of oral Melphalan seems capable to maintain a good response rate with reduction of symptomatic spleen enlargement in more than 50% of patients without excessive toxicity and with a lower rate of BP evolution, as compared to continuous Melphalan administration. Disclosures No relevant conflicts of interest to declare.

AZA In the Treatment of Therapy Related MDS and AML (tMDS/AML): a Report on 60 Patients by the Groupe Francophone Des Syndromes Myelodysplasiques (GFM)

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2911-2911
Author(s):  
Jehane Fadlallah ◽  
Cecile Bally ◽  
Bruno Quesnel ◽  
Norbert Vey ◽  
Francois Dreyfus ◽  
...  
Keyword(s):  
Response Rate ◽  
De Novo ◽  
Early Death ◽  
Poor Response ◽  
Female Gender ◽  
Median Number ◽  
Hematological Toxicity ◽  
Similar Response ◽  
Best Response ◽  
Wbc Count

Abstract Abstract 2911 Background: AZA gives 50–60% responses and improves OS in higher-risk MDS but its role in t MDS/AML, characterized by a high frequency of unfavorable karyotypes and poor response to available treatments, remains unknown. Methods: An AZA compassionate program (ATU) was opened in France between Dec 2004 and Jan 2009 for higher risk MDS, and for AML not candidates to or refractory to intensive chemotherapy (IC). We analyzed t MDS/AML included in this program and having received at least 1 cycle of AZA, excluding patients (pts) previously treated with chemotherapy (CT) for their tMDS/AML. Results: 60 tMDS/AML were included: M/F:24/36, median age 69 (range 20–87). Primary disease was Breast Carcinoma (n=17), CLL (n=6), Hodgkin's disease (n=4), NHL (n=7), ALL (n=2), ovarian (n=2), liver(n=2), prostate carcinoma (n=2), other cancers (n=16), immunosuppressive therapy for lupus or Lung transplant in the last 2 pts. Treatment of primary neoplasm consisted in C×T in 86% and R×T in 61%. Diagnosis (WHO) was RCMD+/− RS in 4 pts, RAEB-1 in 10 pts, RAEB-2 in 28 pts MDS with myelofibrosis in 1 pt, and AML in 17 pts (including 12 FAB RAEBt). IPSS cytogenetics were fav in 4 (6.7%), int in 11 (18.3%), and unfav in 45 (75%, including 71% Complex karyotypes). Patients received a median of 4 cycles (range 1–24) of AZA, at FDA/EMEA-approved schedule (75 mg/m2/d ×7d/4 week) in 73% patients and a less intensive schedule (5d/4w, or <75mg/m2/d) in 27% patients. 25 (41.6%) pts received < 4 cycles, mainly due to early death (32%), failure (28%) or hematological toxicity (16%). Best response according to IWG 2006 criteria was CR in 9 pts (15%), marrow CR (mCR) in 8 (13%), PR in 1, stable disease (SD) with HI in 5 (8%) ie an overall response rate (ORR) of 38%. In pts who received >4 cycles, ORR was 21/35 (60%). Age, WBC count, baseline platelet count, % marrow blasts, karyotype (whatever the categorization) and ECOG status had no impact on ORR. 1, 2 and 3 year survival was 35%, 15% and 7%. Female gender (p=0.02), achievement of response (p=0.003) and ECOG status (0-1 vs 2–4) (p=0.04) had significant impact on OS while karyotype and % marrow blasts had no impact. However, there was a trend for lower OS in patients with chrom 5 abn (2y 0S 7.7% vs 23 %, p=0.08). 9 (15%) patients, all females, median age 55 (range 35–66) were allografted after a median number of 6 AZA cycles (range 2–17), including 3 pts, 4 pts and 2 pts who had achieved CR, mCR and no response to AZA, respectively. 4 (44%) of them were alive after 5+,17+,32+ and 42+ months. By comparison to the 232 pts with de novo MDS/AML included in the same program, tMDS/AML had a higher frequency of complex karyotype (71 vs 29.5, p<0.01), received fewer cycles of AZA (4 vs 6, p=0.0014) due to more frequent discontinuation of AZA before 4 cycles (41.6% vs 25%, p=0.025) mainly related to a higher incidence of early deaths. tMDS/AML had a similar response rate (38% vs 45% in de novo MDS/AML, p=0.67), but significantly shorter OS (2yOS 15% vs 33.3, p=0.003, figure 1). Conclusion: In this cohort of tMDS/AML, survival with AZA was shorter than in de novo MDS/AML, probably largely due to their more severe baseline characteristics. Only 15% of tMDS/AML could be allografted, half of them with so far a favorable outcome. Disclosures: Fenaux: CELGENE, JANSSEN CILAG, AMGEN, ROCHE, GSK, NOVARTIS, MERCK, CEPHALON: Honoraria, Research Funding.

Activity and safety of cabozantinib (cabo) in brain metastases (BM) from metastatic renal cell carcinoma (mRCC): An international multicenter study.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 310-310
Author(s):  
Laure Hirsch ◽  
Nieves Martinez Chanza ◽  
Subrina Farah ◽  
Ronan Flippot ◽  
Nityam Rathi ◽  
...  
Keyword(s):  
Response Rate ◽  
Local Therapy ◽  
Median Number ◽  
Clinical Activity ◽  
Recist 1.1 ◽  
Kaplan Meier ◽  
Best Response ◽  
Radiological Response ◽  
Modified Recist ◽  
International Multicenter Study

310 Background: Cabo shows robust clinical activity in mRCC. Patients (pts) with BM have been underrepresented in clinical trials and effective systemic therapy is lacking. We retrospectively characterized the clinical activity and toxicity of cabo in pts with BM from RCC. Methods: Consecutive medical records from mRCC pts with BM treated with cabo monotherapy across 15 institutions were reviewed. Pts were grouped by radiologic presence (cohort 1) or absence (cohort 2) of progressing intracranial metastases. Brain-directed local therapy was allowed but radiological confirmation of intracranial progression at cabo start was required in cohort 1. Radiological response rate was investigator-assessed by modified RECIST 1.1 for intracranial and RECIST 1.1 for extracranial responses. Time to treatment failure (TTF) and overall survival (OS) were estimated by Kaplan-Meier. Results: We identified 69 pts with BM from RCC, 25 (36%) in cohort 1 and 44 (64%) in cohort 2. Majority were IMDC intermediate/poor (87%) and received cabo as ≥2nd line (75%). Median time from mRCC diagnosis to BM was 19.1 months (mos) (IQR 4.4-39.5). Overall, median number of BM was 3 (range 1-27) and median size of largest lesion was 1.2 cm (range 0.2-6.6) with frontal (62%) and parietal (48%) as the most frequent localizations. Prior brain directed therapy was used in 65% and 93% of pts in cohort 1 and 2 respectively. Median follow-up after cabo initiation was 11 mos (range 4-72). Twenty three percent of pts remained on therapy while 52% discontinued for progression and 9% for toxicity. Intracranial response rate was 61% (95%CI 39%-80%), with 3 complete responses, for cohort 1 and 57% (95%CI 41%-72%) for cohort 2. Only 10% (n = 7) had intracranial progression as best response. For cohort 1, extracranial response was 52% (95%CI 31%-72%), median TTF was 9.9 mos (95%CI 5.9-14.0) and OS was 14.7 mos (95%CI 7.7-23.0). For cohort 2, extracranial response was 41% (95%CI 26%-57%), TTF was 9.0 mos (95%CI 4.6-11.4) and OS was 14.1 mos (95%CI 11.0-22.0). Most common adverse events were fatigue (77%) and diarrhea (46%). Eight pts received concomitant brain-directed treatment during cabo therapy without neurological toxicities. Conclusions: Cabo shows significant intracranial activity and acceptable safety profile in pts with BM from RCC. [Table: see text]

A Phase II Study of Decitabine In Advanced Chronic Myelomonocytic Leukemia (CMML)

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1873-1873
Author(s):  
Thorsten Braun ◽  
Nathalie Droin ◽  
Benoit de Renzis ◽  
Francois Dreyfus ◽  
Kamel Laribi ◽  
...  
Keyword(s):  
Phase Ii ◽  
Conflicts Of Interest ◽  
Cytogenetic Response ◽  
Median Number ◽  
Costal Margin ◽  
Monocyte Count ◽  
Blood Monocytes ◽  
Grade 3 ◽  
Wbc Count

Abstract Abstract 1873 Background: CMML, now classified among MDS/MPN, is prognostically heterogeneous. We (JCO 1988 6:1417, Blood 1996 88:2480) and others found prognosis in CMML to depend on both “MDS factors” (% marrow blasts, cytopenias, karyotype) and “MPN” factors, ie splenomegaly (SMG), WBC count, extramedullary disease (EMD). Treatment of advanced CMML is difficult. The hypomethylating agents Azacitidine and Decitabine (DAC) have shown efficacy in CMML, but in prognostically heterogeneous cohorts. We conducted a phase II trial of DAC in a well defined cohort of advanced CMML. Methods: To be included, CMML (according to WHO) should have: if WBC<13G/l an IPSS≥1.5; if WBC≥13G/l, two of the following criteria: marrow blasts≥5%, Hb<10g/dl, plts<100G/l, abnormal cytogenetics, SMG >5cm below costal margin, (SMG>5cm), EMD, based on our previous prognostic factors. Pts received DAC 20mg/m2/d IV for 5 days every 28 days for at least 3 cycles. Response criteria were based on IWG 2006 for pts with WBC <13G/L and for pts with WBC > 13 G/L also included evolution of WBC, SMG and EMD (Blood 1996 88:2480). Results: Between Nov 2008 and June 2009, 41 pts were included in 16 centers, of whom 39 completed at least one cycle and were considered evaluable for response (the 2 other pts died from septic shock before and during the first cycle respectively). Median number of cycles was 9 (range 1–17). Median age was 71 years (range 54–88), M/F:30/9. Seventeen pts had CMML 1 and 22 had CMML 2 (including pts with up to 29% marrow blasts). Median WBC count was 29.5G/l (range 4.1–147.3), median blood monocytes 3G/l (range 1.05–95.7), and median BM blasts 10% (1-29). Nine pts had WBC<13G/l and 30 WBC≥13G/l. Abnormal karyotype was found in 18 (46.2%) pts, including +8 and -7 in 7 and 1 case, respectively. 15 pts (38.6%) had SMG>5cm and 8 (20.5%) EMD involving skin (n=5) and lymph nodes (n=3). Overall Response Rate (ORR,) was 38.6% with 4 (10.3%) CR, 8 (20.5%) marrow CR and 3 (7.7%) Stable Disease (SD) with HI. 1 CR pt received allo SCT. 18 (46%) pts had SD without HI and 6 (15.4%) pts progressed to AML. 8 (36.4%) of the 22 RBC transfused pts became RBC transfusion independent. 3/10 (30%) pts with plt<50G/l reached plt>100G/l. Four pts had cytogenetic response (3 CR and 1 PR) exclusively among pts with +8. Median peripheral monocyte count decreased from 4.8G/l to 0.3G/l after 3 cycles of DAC among responders. SMG disappeared in 6/15 (40%) pts and EMD in 6/8 (75%) pts. 16 pts were receiving Hydroxyurea (HY) at inclusion which could be stopped in 12 of them. With a median follow up of 10 months (1-18), 7 pts had died from progression (n=3), sepsis (n=3) and unrelated cause (n=1). Overall Survival (OS) estimate was 60% at 2 years (median not reached). By comparison, in our previous trial of HY in CMML where inclusion criteria were the same, 2 year survival was 43% (median OS 20 months; Blood 1996 88:2480), for a median follow up of 11 months (range1-43). The only factor associated with response to DAC was WHO subtype, CMML 2 pts showing significantly better ORR (30.8% vs 7.7% in CMML 1; p=0.041).There was no difference in survival between CMML 1 and 2 pts. Treatment with DAC was generally well tolerated with, except for usual grade 3/4 cytopenias, and grade 3 fatigue (n=1). Conclusion: DAC is active in advanced CMML and safe in these elderly pts. A possibly better survival than with HY will have to be confirmed in randomized trials. Correlative genetic studies identifying markers potentially predicting response and survival for DAC are currently underway in our lab. Disclosures: No relevant conflicts of interest to declare.

Phase I-II Trial of Oral Cyclophosphamide, Prednisone and Lenalidomide (Revlimid®) (CPR) for the Treatment of Patients with Relapsed and Refractory Multiple Myeloma

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3055-3055
Author(s):  
Donna E. Reece ◽  
Esther Masih-Khan ◽  
Arooj Khan ◽  
Saima Dean ◽  
Sharon Fung ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Dose Level ◽  
Research Funding ◽  
Response Rate ◽  
Objective Response ◽  
Median Number ◽  
Prior Therapy ◽  
Best Response ◽  
Level 3 ◽  
Grade 3

Abstract Abstract 3055 Lenalidomide (Revlimid®) and dexamethasone is an effective regimen for relapsed/refractory (rel/ref) multiple myeloma (MM) patients (pts) with an overall response rate of 60% and median time to progression of 13.4 months (Dimopoulos ME, et al. Leukemia 2009; 23: 2147-52). We combined lenalidomide with the alkylating agent combination of cyclophosphamide and prednisone—an older regimen with minimal cumulative myelosuppression and good activity as second or third line therapy (Trieu Y, et al, Mayo Clin Proc 2005; 80: 1582). The CPR regimen consisted of cyclophosphamide (CY) on days 1, 8, and 15, lenalidomide on days 1–21 and prednisone 100 mg q 2 days in a 28-day cycle. ASA 81 mg/day was given as DVT prophylaxis. Three dose levels were evaluated using a 3 × 3 dose escalation design. Thirty-two pts were entered between 11/2007-06/2009; median age was 64 (42-80) yrs, 60% were male, and immunoglobulin isotype was IgG in 19 (62%), IgA in 8 (25%) and light chain in 4 (13%) pts. Median β2-microglobulin level was 257 (92-767) nm/L, albumin 39 (34-48) g/L, creatinine 83 (50-126) μmol/L, platelet count 355 (75-479) × 109/L and ANC 2.5 (1.1-6.1) × 109/L. The median number of prior regimens was 2 (1-5). Prior therapy included: ASCT (single in 91%; double in 19%), thalidomide (28%) and bortezomib (50%). FISH cytogenetics were available in 13 pts; 1 had del 13q but none had t(4;14) or del p53. Table 1 summarizes protocol treatment delivered. Table 1. Dose level N Cyclophosphamide dose (mg/m2) Lenalidomide dose (mg) Prednisone dose (mg) Median # cycles given 1 3 150 15 100 12 (12–34+) 2 3 150 25 100 10 (9–23) 3 26 300 25 100 17 (5–28+) 1–3 (All) 32 150–300 15–25 100 19 (5–34+) Dose limiting toxicity was not observed during cycle 1 at any dose level. Grade 3–4 toxicities during the trial included: thrombocytopenia in 7 (22%) and neutropenia in 9 (29%), managed with dose reduction and/or growth factors; five episodes of febrile neutropenia occurred, all at dose level 3. In cohort 3, other grade 3–4 non-hematologic toxicities included 1 episode each of abdominal pain/bacteremia, hypokalemia, fatigue, sick sinus syndrome, cardiac amyloidosis, perforated diverticulum and 2 episodes of DVT. Two heavily pretreated pts developed 2° MDS, including 1 previously treated for lymphoma, 43 and 190 mos after the diagnosis of MM. The best response using modified EBMT criteria was documented at a median of 7 (1-26) cycles and included the following: dose level 1 (1 CR, 2 PR); dose level 2 (1 VGPR, 2 PR); dose level 3 (4 CR, 14 VGPR, 11 PR, 1 MR and 1 stable disease). At a median F/U of 16 (5-34) months, 13 pts remain on study and 18 have progressed at a median of 10 (2-23) mos; 1 was lost to F/U and 9 have died of progressive MM. The 1-year actuarial OS and PFS rates are 93% (95% CI 76–98%) and 78% (95% CI 60–89%), respectively. We conclude: 1) the combination of full doses of the agents in CPR can be given in a 28 day cycle with an acceptable safety profile; 2) the objective response rate (CR + PR + MR) in all 32 pts to date is 94%; 3) the 1-year OS of 93% and PFS of 78% compare favorably with other 3-drug combinations in rel/ref MM pts; 4) further evaluation of this regimen in newly diagnosed pts would be of interest. Disclosures: Reece: Celgene: Honoraria, Research Funding. Off Label Use: Combination of lenalidomide and cyclophosphamide and prednisone in relapsed and refractory myeloma patients. Chen:Celgene Corporation: Consultancy, Honoraria, Research Funding. Kukreti:Celgene: Honoraria.

Influence of Stem Cell Mobilization After Cyclophosphamide, Thalidomide and Dexamethasone (CTD) Regimen in Patients with Newly Diagnosed Multiple Myeloma

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1927-1927
Author(s):  
Jae-Sook Ahn ◽  
Deok-Hwan Yang ◽  
Sung-Hoon Jung ◽  
Soo-Young Bae ◽  
Yeo-Kyeoung Kim ◽  
...  
Keyword(s):  
Stem Cell ◽  
Induction Therapy ◽  
Response Rate ◽  
Conflicts Of Interest ◽  
Median Number ◽  
High Response Rate ◽  
Cell Yield ◽  
Newly Diagnosed ◽  
Cd34 Cells ◽  
Cell Mobilization

Abstract Abstract 1927 Backgrounds: CTD regimen has been known as an effective induction therapy in patients with newly diagnosed MM. But, there were inconsistent results for the autologous stem cell yield for transplantation. The aim of present study was to identify the influence of CTD therapy on outcome of peripheral blood stem cell (PBSC) collection. Methods: Forty-eight patients received 4 cycles of CTD therapy. Stem cells were mobilized with cyclophosphamide (3.0 g/m2) and G-CSF (10 ƒÝg/kg, daily) or G-CSF alone. Patients failing to collect ≤ 4.0 × 106 CD34+ cells /kg received a second mobilization courses. Results: The median age at diagnosis was 56 years (range, 39–69). Median duration from start of CTD therapy to first collection was 4.6 months (range, 3.3–8.7). Forty-four patients were mobilized with cyclophosphamide following with G-CSF and 4 patients with G-CSF alone. The median day of apheresis was 3 days (range, 2–7). The response rate for CTD regimen at mobilization was 10% (5/48) of CR, 25% (12/48) of VGPR and 63% (30/48) of PR. A median number of harvested CD34+ cells was 8.6 × 106 cells/kg. At the first mobilization, 83% (40/48) of patients had been reached the minimal PBSC collection target of ≥ 2.0 × 106 CD34+ cells/kg and 71% (34/48) of patients achieved the collection ≥ 4.0 × 106 CD34+ cells/kg. At the end of second mobilization, 90%(43/48) of patients had yields of at least ≥ 2.0 × 106 CD34+ cells/kg and 77% (37/48) of patients had yields of ≥ 4.0 × 106 CD34+ cells/kg. During mobilization period, three patients were developed grade 3/4 non-hematologic adverse events. Conclusion: CTD regimen is an effective induction therapy in patients with newly diagnosed MM showing high response rate and acceptable rate of autologuos stem cell yield without any detrimental effect for the following stem cell collection. Disclosures: No relevant conflicts of interest to declare.

Low Toxicity Profile of the Combination of Bendamustine Plus Rituximab (BR) in Elderly FRAIL Patients with Newly Diagnosed DLBCL

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4429-4429
Author(s):  
Michele Spina ◽  
Stefano Luminari ◽  
Flavia Salvi ◽  
Francesco Passamonti ◽  
Alberto Fabbri ◽  
...  
Keyword(s):  
Elderly Patients ◽  
Response Rate ◽  
Conflicts Of Interest ◽  
Hematological Toxicity ◽  
High Risk Population ◽  
Toxicity Profile ◽  
Newly Diagnosed ◽  
Frail Patients ◽  
Low Toxicity ◽  
Grade 3

Abstract Introduction: R-CHOP is the gold standard for the treatment of elderly patients with DLBCL. However, unfit and frail patients frequently do not qualify for CHOP-based chemotherapy. Alternatives are an urgent medical need. Bendamustine plus rituximab (BR) has been established as a standard treatment of indolent lymphomas and preliminary data have shown a promising activity in DLBCL, both in the relapsing and upfront setting. Methods: Within the Fondazione Italiana Linfomi (FIL), we started a phase II study (R-BENDA frail study, EUDRACT2011-001421-24) in elderly patients (>70 years) with a newly diagnosed DLBCL not suitable for R-CHOP-based chemotherapy. All patients were evaluated according to ADL, IADL and CIRS-G and were considered FRAIL if the following criteria were meet: in patients aged 70-80 ADL<4 or IADL<5 or one grade 3 comorbidity or >8 grade 2 comorbidities; in patients older than 80 years ADL>5 or IADL>6 or 5-8 grade 2 comorbidities. Patients received bendamustine at a dose of 90 mg/m2 daily on days 1 and 2 of each 28-day cycle along with rituximab on day 1 for up to 6 cycles. Results: From February 2012 to February 2014, 49 patients were enrolled in 24 Italian centers. The majority (57%) were male and 57% had stage III-IV with 41% elevated LDH. The median age was 82. Overall, 83% of the planned cycles were delivered without dose reduction or delay; grade 3/4 neutropenia was reported in 25% of cycles followed by anemia 21%, and thrombocytopenia 20%. One case of febrile neutropenia was observed. Grade 3-4 non-hematological toxicity was mild and reported in 6% of cycles including 3 episodes of cardiovascular events and 7 other cases of different toxicities (one creatinine increase, one fatigue, one bleeding, one peripheral neurotoxicity, one hyponatriemia, one hyperglycemia and one liver toxicity). Two deaths during treatment have been observed (cardiac failure and sudden death). At the interim analysis (23 patients) the overall response rate was 56% with a complete response rate of 39%. Conclusions: Combination therapy with BR demonstrates low toxicity profile in this high risk population. The promising results on activity can encourage clinicians to considered BR for the treatment of FRAIL elderly patients with DLBCL not eligible for R-CHOP. Disclosures No relevant conflicts of interest to declare.

Gemcitabine in Combination with Oxaliplatin (GEMOX) As a Salvage Regimen in Patients with Relapsed/Refractory Hodgkin's Lymphoma

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1517-1517 ◽  
Author(s):  
Evren Ozdemir ◽  
Alma Aslan ◽  
Alev Turker ◽  
Ibrahim Barista ◽  
Ayse Kars
Keyword(s):  
Hodgkin’S Lymphoma ◽  
Overall Response Rate ◽  
Response Rate ◽  
Median Number ◽  
Hodgkin's Lymphoma ◽  
Hematological Toxicity ◽  
Hematologic Toxicity ◽  
Refractory Disease ◽  
Salvage Regimen ◽  
Overall Response

Abstract This study's objective was to evaluate the efficacy and safety of gemcitabine in combination with oxaliplatin (GEMOX) as a salvage regimen in patients with relapsed or refractory Hodgkin's lymphoma. Twenty-five patients were enrolled. All patients had received ≥ 2 prior chemotherapy regimens, had an ECOG performance status ≤ 2 and had adequate organ function. Patients received intravenous gemcitabine (1000 mg/m2) and oxaliplatin (100 mg/m2) on days 1 and 15, every 4 weeks. The median age was 29 years (range, 18-64) and 16 (68%) were male. Twenty-one (84%) had primary refractory disease (n=13) or relapsed within 12 months after initial therapy (n=8). All had previous platinum-based salvage chemotherapy (ICE, 23; DHAP, 2). Ten patients (40%) had relapsed/refractory disease following autologous stem cell transplantation (SCT). None had previous brentuximab vedotin treatment. Twenty-one (84%) patients were refractory or progressive on the last treatment. Median number of previous lines of chemotherapy was 2 (range, 2-4). Median number of GEMOX cycles administered to the patients was 3 (range, 2-6). Treatment response was evaluated with PET-CT before and 2-3 cycles after treatment, and those patients who demonstrated a response continued to receive a maximum of 6 courses of GEMOX or bridged to SCT. Of 25 patients, 2 (8%) had complete response, 9 (36%) had partial response and the remaining patients had refractory/progressive disease with an overall response rate of 44%. Seven of the 10 patients who had relapsed/refractory disease after autologous SCT achieved a response (CR, 2; PR, 5). The median time to progression for responding patients was 3 months (range, 1-40 months). One patient is disease free for 40 months. Three patients were successfully bridged to SCT (autologous, 2; allogeneic, 1). Main toxicity was hematological. Grade ≥ 3 hematologic toxicity occurred in 10 patients: thrombocytopenia (36%), neutropenia (16%) and anemia (8%). Among these, 7 had previous autologous SCT. One patient had grade 4 neutropenia and thrombocytopenia. Treatment cycle postponed in 6 patients without dose reduction because of hematological toxicity. Seven patients (28%) needed G-CSF support. One patient developed febrile neutropenia. No treatment-related deaths occurred. GEMOX was shown to be an effective salvage regimen in patients with relapsed/refractory Hodgkin's lymphoma, producing an overall response rate of 44%. It is an active regimen in patients who had relapsed/refractory disease after autologous SCT. Although, the median PFS time was short, some patients can be bridged to SCT and some can get long-term PFS. Hematological toxicity was common, especially in patients with previous autologous SCT. Disclosures Off Label Use: Gemcitabine in Hodgkin's Lymphoma Oxaliplatin in Hodgkin's Lymphoma.

A Phase I-II Study of the Efficacy and Safety of Lenalidomide (LEN) Combined to Azacitidine (AZA) in Higher Risk MDS and AML with Del 5q - a Study By the Groupe Francophone Des Myelodysplasies (GFM)

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2892-2892 ◽  
Author(s):  
Lionel Ades ◽  
Christian Récher ◽  
Julie Lejeune ◽  
Aspasia Stamatoullas ◽  
Marie Sebert ◽  
...  
Keyword(s):  
Phase I ◽  
Primary Endpoint ◽  
Research Funding ◽  
Response Rate ◽  
Early Death ◽  
Complete Response ◽  
Cytogenetic Response ◽  
Median Number ◽  
Intensive Chemotherapy ◽  
Best Response

Abstract Background: Higher risk MDS and AML with del(5q) carry very poor prognosis, but show some response to AZA and LEN as single agents (Adès Blood 2009, Itzykson, Blood 2010). The combination of LEN and AZA has been tested in non-del 5q MDS patients with encouraging results and limited toxicity (Sekeres, Blood 2012). Sequential combination of AZA and LEN has also shown to be feasible and potentially effective in 20 patients with higher-risk MDS with del(5q) in a phase I study (Platzbecker, Leukemia 2013). In this phase I-II trial, we combined escalating doses of LEN to AZA in higher risk MDS and AML with del(5q). Methods: Patients with IPSS int-2 or high MDS, CMML with WBC < 13,000/mm3 and marrow blasts > 10% and AML (20-30% marrow blasts) with 5q deletion with or without additional cytogenetic abnormalities could be included provided they had not previously received LEN or AZA. Patients should also have contra indication to intensive chemotherapy (IC), precluding inclusion in a GFM competing trial combining IC and LEN in higher risk MDS and AML with del 5q. In the present trial, patients received AZA (75 mg/m2 x5 d, every 28 days) combined with escalating doses of LEN (5 mg/d x14 d in cohort 1, 5 mg/d x21 d in cohort 2 and 10 mg/d x21 d in cohort 3). For patients in hematological CR, PR, HI or marrow CR (MDS) and CR or PR (AML) after cycle 2 or 4, treatment was to be continued at the same schedule unless unacceptable toxicity or overt progression occurred. The primary endpoint was response assessed according to IWG 2006 criteria. Secondary endpoints were best response over the 4 cycles and survival. Medians [IQR] are reported unless specified. Intent-to-treat analyses were made. Results: 49 patients were enrolled, including 15, 10 and 24 patients in cohort 1 (LEN 5 mg/d x14d), 2 (LEN 5 mg/d x21d) and 3 (LEN 10 mg/d x21d). 24 were males and the median age was 69 (63-74). According to WHO classification, 1 patient had CMML, 9 RAEB1, 22 RAEB2 and 17 AML. PS was 0, 1 and 2, in 30.8%, 43.6% and 25.6% patients, respectively. However, as said above, patients included in this trial were considered unfit for IC due to their age and/or comorbidities (cardiovascular in 30 patients, pulmonary e in 10, and neurological in 6 pts). Del(5q) was isolated in only 8.3% pts, while 85.4% had del (5q) and at least 2 additional abnormalities (i.e., complex).. IPSS was int-2 in 33% patients and high in 66% patients. Overall, 143 cycles were administered (median 2/patient, including 9 patients who received 6 or more cycles). In the three cohorts, the median number of cycles received was 2 (1-2), 2 (1-4.75) and 4 (2-5.5) respectively. Fifteen (30.6%) patients discontinued treatment before the second cycle, due to early death (n=9), adverse events (n=3), progression (n=2), or CNS hemorrhage (n=1). They were all considered as non responders (primary endpoint). After 2 cycles, 4 (8.2%) achieved CR, 4 (8.2%) marrow CR and 4 (8.2%) stable disease with hematological improvement (ORR= 24%). The best response rate over the 4 courses was 2/15 (13.3%) in cohort 1, 1/10 (10%) in cohort 2, and 9/24 (37.5%) in cohort 3 (ORR=24%). The response rate was 37.5% in patients receiving 10 mg/d, versus 12% in those receiving 5 mg (p=0.051) while other baseline parameters had no impact on response: IPSS (p=0.073), marrow blasts >10% (p=0.16), sex (p=0.74), cytogenetic complexity (p=0.26) or PS (p=0.419). 2/6 CR patients achieved cytogenetic complete response: 0/2 in cohort 1, 0/0 in cohort 2, and 2/4 in cohort 3. One year OS was estimated at 22.9% [95% IC: 12.3-42.5]. We failed to identified any prognostic factor associated with OS (IPSS (p=0.52), marrow blasts >10% (p=0.28), sex (p=0.99), isolated del(5q) (p=0.68), cohort (p=0.2) and PS (p=0.33)). Regarding toxicity, 58 SAEs (grade 3-4) were reported in 38 patients, including 35 infectious events, 7 bleding events, 3 deep venous thrombosis. Conclusion: In this elderly population of higher risk MDS or AML considered unfit for intensive chemotherapy, and with del 5q that was part of a complex karyotype in almost all cases, the combination of AZA with escalated doses of LEN was associated with early discontinuation (<4 cycles) in 30/49 (61.2%) of the patients, mostly due to progression or toxicity, and only 12/49 (24.5%) response. The fact that some responders also achieved cytogenetic response may however be encouraging. Disclosures Vey: Janssen: Honoraria; Celgene: Honoraria; Roche: Honoraria. Park:Hospira: Research Funding; Celgene: Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding. Fenaux:Amgen: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Celgene Corporation: Honoraria, Research Funding; Janssen: Honoraria, Research Funding.

Pemetrexed and carboplatin plus bevacizumab for advanced non-squamous non-small cell lung cancer (NSCLC): Preliminary results

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7601-7601 ◽  
Author(s):  
J. D. Patel ◽  
T. A. Hensing ◽  
V. Villafor ◽  
E. Hart ◽  
P. Bonomi
Keyword(s):  
Bowel Perforation ◽  
Previous History ◽  
Median Number ◽  
Hematological Toxicity ◽  
Prior History ◽  
Toxicity Profile ◽  
Common Grade ◽  
History Of ◽  
Grade 3 ◽  
Number Of Cycles

7601 Background: Pemetrexed in combination with carboplatin has been shown to have promising activity and favorable toxicity profile in NSCLC. Bevacizumab has been shown to improve response rates and survival in pts with advanced non-squamous NSCLC when combined with carboplatin and paclitaxel. This study of pemetrexed and carboplatin plus bevacizumab was designed to evaluate the toxicity profile and to estimate the activity of the regimen in this pt population. Methods: Eligibility required that pts were chemotherapy-naive, had stage IIIB (effusion)/IV non-squamous NSCLC, PS 0–1, with no evidence of CNS metastases. Pts received pemetrexed 500 mg/m2 over 10 minutes, carboplatin AUC 6 over 30 minutes, and bevacizumab 15 mg/kg over 30–90 minutes on a 21-day cycle for 6 cycles. Pts with SD or PR received pemetrexed 500 mg/m2 and bevacizumab 15 mg/kg every 21 days until disease progression or toxicity. All pts received folic acid, vitamin B12 and steroid prophylaxis. Results: From 8/05 to 9/06, 39 pts (of planned 50) were enrolled: 20 M/19 F; median age 64 (range 41 - 80). One pt enrolled and subsequently refused treatment. Median number of cycles was 6 (range 1–22), and 25/38 (66%) completed at least 6 cycles of therapy. There was no grade 4 hematological toxicity. Grade 3 hematological toxicities were anemia (5%, N=2) and thrombocytopenia (3%, N=1). The most common grade 3/4 non-hematological toxicities included proteinuria (3%, N=1, gr 3), venous thrombosis (3%, N=1, gr 3), infection (3%, N=1, gr 4), and diverticulitis (11%: 8%, N=3, gr 3/3%, N=1, gr 4). 1 pt with diverticulitis experienced bowel perforation that required surgical intervention. The trial was temporally suspended and the group of pts with diverticulitis was analyzed separately. The only risk factor identified was previous history of diverticulitis. One CR, 20 PRs were observed for an overall response rate of 55% (95%, CI 43–75%). Conclusions: Treatment with pemetrexed and carboplatin plus bevacizumab in pts with advanced non-squamous NSCLC is feasible with an acceptable toxicity profile. The encouraging activity justifies further development of this regimen. However, pts with a prior history of diverticulitis should be excluded until this observation can be investigated further. No significant financial relationships to disclose.

Doxil (D), Vincristine (V), Reduced Frequency Dexamethasone (d) and Revlimid(R) (DVd-R) Results in a High Response Rate in Patients with Refractory Multiple Myeloma (RMM).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2559-2559 ◽  
Author(s):  
Rachid Baz ◽  
Toni K. Choueiri ◽  
Rony Abou Jawde ◽  
Bridget McGowan ◽  
Yvette Ellis ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Median Time ◽  
Progressive Disease ◽  
Response Rate ◽  
Median Number ◽  
High Response Rate ◽  
High Response ◽  
Chemotherapeutic Regimen ◽  
Best Response ◽  
Grade 3

Abstract Background: The combination of DVd with Thalidomide (T) results in a high response rate (greater than 80% with about 50% of patients achieving a CR or NCR) in multiple myeloma. Revlimid, an immunomodulatory drug (IMiD) is active in patients with MM. We previously reported on a phase I trial of DVd-R in patients with MM, in which the maximum tolerated dose of R was 10mg daily. Methods: The DVd-R regimen was given as follows: on day 1 D was given at 40 mg/m2 IVPB; V at 2 mg IVP; d at 40 mg PO daily for 4 days, R was started at 10mg daily. R was given for 21 days consecutively. For the first cycle R was started 7 days prior to chemotherapy, while it was started on day 1 on subsequent cycles (cycle 1 was 35 days). DVd was planned every 28 days for 2 cycles after best response or a minimum of 4 cycles. Maintenance therapy consisted of R +/− Prednisone 50 mg Qod. All patients received amoxicillin, acyclovir and aspirin 81mg prophylactically. Responses were assessed based on the criteria set forth by SWOG. Patients: The study accrued 58 patients to date (36 refractory and 22 relapsed patients), 45 are evaluable for response. The median patient age at the start of the study is 62 years and 74% are males. The median number of prior chemotherapeutic regimen is 3 (range 1–7), 67% of patients had progressed after a Thalidomide containing regimen, 70% had received a VAD like regimen and 17% had received a prior autologous stem cell transplant. The median time from diagnosis to study entry is 39 month (range 5–182). Eighty six percent had Durie Salomon stage III. The mean serum B2microglobin was 6.6mg/dL (s.d.4.2). Results: The median number of cycles of DVd-R delivered was 4. Of evaluable patients, 6 patients had a CR (13%), 5 had a NCR (11%), 16 had a PR (35%), 11 had stable disease (24%), and 7 had progressive disease (15%) as their best response. The median time to best response was 38 days. After a median follow up of 7.3 month (range 0–24 months), 23 patients had progressive disease and 16 patients had died. Fifty two percent of refractory patients (19/36) had a response on DVd-R. Grade 3 and 4 leukopenia occurred in 24% and 15% respectively, however febrile neutropenia occurred in only 1 patient. Grade 3 and 4 infections occurred in 26% and 3% respectively (all but one were pneumonia). Grade 3 thrombocytopenia occurred in 20%. Venous thromboembolic events occurred in 5 patients (9%) (2 patients with pulmonary embolus and 4 with deep venous thrombosis). Grade 3 neuropathy occurred in 3 patients (no patients had grade 4 neuropathy). Two patients developed grade 3 tumor lysis syndrome. Conclusion: DVd-R is an effective chemotherapeutic regimen in patients with RMM who progressed or did not respond to VAD like regimens or to Thalidomide containing regimens, produces a high response rate among chemotherapy resistant patients, and has a manageable toxicity profile. The results will be updated at the time of the meeting.

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