Plasmablastic Lymphoma Is Curable The HAART Era. A 10 Year Retrospective By The AIDS Malignancy Consortium (AMC)

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1801-1801 ◽  
Author(s):  
Ariela Noy ◽  
Amy Chadburn ◽  
Shelly Y. Lensing ◽  
Page Moore
Keyword(s):  
Initial Diagnosis ◽  
Stage I ◽  
Plasmablastic Lymphoma ◽  
High Dose ◽  
Refractory Disease ◽  
Newly Diagnosed ◽  
Grade 3 ◽  
One Year ◽  
Experienced Grade

Abstract Background The highly aggressive plasmablastic lymphoma (PBL), originally described almost exclusively in HIV+ patients, was nearly uniformly fatal in the pre-HAART era. We hypothesized that aggressive chemotherapy and HAART could result in cures. Methods We retrospectively analyzed baseline characteristics, treatment patterns and outcomes of patients (pts) with PBL treated at multiple centers within the AIDS Malignancy Consortium (AMC). HIV positivity was not required. 19 confirmed PBLs from 9 national AMC sites diagnosed between 1999 and 2008 were evaluated. Results 17/19 patients (pts) with confirmed PBL were HIV+. Data was captured at initial diagnosis on 12 pts (all HIV+) and 7 with relapsed/refractory disease (5 HIV+). HAART status at PBL initial diagnosis was 33% on, 58% off, and unknown 8%. Median CD4 count 110 (range 4-658). First line chemotherapy was given to 10/12 (83%) newly diagnosed patients with stage I/II (6) vs III/IV(6) disease. This was CHOP(4), CDE (1), EPOCH (2) and EPOCH with high dose methotrexate and zidovudine (2). Second line therapy was given to 5/7 relapsed/refractory patients with stage I (1) vs Stage III/IV (5) disease and a median CD4 83 (range 10-202): EPOCH alternate HD Mtx+AZT (n=1); Hyper-CVAD (n=2); High dose Mtx + AZT (n=1); VACOP-B(n=1). One pt underwent BEAM based autologous stem cell transplant. For both groups combined, 6 patients experienced grade 3/4 toxicity. Febrile neutropenia was the most common grade 3/4 toxicity (4 patients) followed by thrombocytopenia (3 patients). One patient with refractory disease experienced grade 5 toxicity. For the 12 newly diagnosed patients, 8 patients were alive at last follow-up and 4 had died. Median follow-up for survivors was 73 (range, 40-165) weeks. One-year survival was 66.7% (SE, 13.6). See Figure 1. For the 7 relapsed/refractory patients, 2 patients were alive at 24 and 54 weeks, and 1 was lost to follow-up. One-year survival was 53.6% (SE, 20.1%). Conclusions In the HAART era, aggressive treatment of PBL can result in significant survival times. However, determination of the superior treatment regimen could not be determined from this small patient sample. CTSU 9177 is prospectively studying PBL with EPOCH. Disclosures: No relevant conflicts of interest to declare.

Phase II study of low dose (LD) and high dose (HD) premarin in androgen independent prostate cancer (AIPC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 4560-4560 ◽  
Author(s):  
M. Pomerantz ◽  
J. Manola ◽  
M. Taplin ◽  
G. Bubley ◽  
M. Inman ◽  
...  
Keyword(s):  
Warfarin Dose ◽  
High Dose ◽  
Clinical Predictors ◽  
Predictors Of Response ◽  
Psa Response ◽  
Transdermal Estradiol ◽  
Gi Toxicity ◽  
Grade 3 ◽  
Experienced Grade

4560 Background: Estrogens, including DES, transdermal estradiol, estramustine and PC-SPES, have shown antitumor activity in AIPC. We tested two doses of Premarin to determine efficacy and safety of this commonly available estrogen. Methods: Patients with progressive AIPC were eligible. Prior estrogen use, significant cardiac or thromboembolic disease, and concurrent steroids were not allowed. Patients were randomized to Premarin 1.25 mg once (LD) or 3 times (HD) daily. Prophylactic breast irradiation was encouraged and warfarin 1 mg daily was required, unless contraindicated. After the first stage of accrual, the LD arm was closed because of limited activity, while the HD arm continued to the 2nd stage. Results: 46 patients were enrolled; 17 patients were randomized to LD Premarin, 29 patients assigned to HD Premarin by randomization or direct assignment. One patient withdrew consent prior to therapy. Median follow up is 5.3 months. Median age was 69 years (range 52–86) and median PSA 84.6 ng/ml (range 2.5–794.1). 19 patients (41%) had measurable disease. PSA declines ≥ 50% were seen in 0% (95% C.I., 0–19.5) and 32.1% (95% C.I., 15.9–52.4) of patients treated with LD and HD premarin. 1 patient treated with HD Premarin had a partial measurable response (8.3%; 95% C.I., 0.2–38.5). Median time to progression was 3.3 and 3.2 months in the LD and HD arms, respectively. Premarin was well tolerated in 45 evaluable patients. One grade 4 toxicity was noted, a stroke in the LD arm. Grade 3 toxicity was rare with 1 allergic reaction, 2 DVTs and 3 episodes of GI toxicity in one patient. Two patients experienced grade 3 elevations in PT requiring modification of warfarin dose. No significant gynecomastia was reported. Analysis of serially drawn hormone levels and molecular correlates of treatment response is pending. Conclusions: HD Premarin is associated with a 32.1% PSA response rate, while no responses were seen with LD Premarin. A measurable response was noted in 1 of 12 patients treated with HD Premarin. Toxicity was modest, though thromboembolism was seen even with prophylactic warfarin. Ongoing studies are evaluating molecular and clinical predictors of response. No significant financial relationships to disclose.

scholarly journals Bortezomib Maintenance Therapy after Induction with R-CHOP, ARA-C and Autologous Stem Cell Transplantation in Newly Diagnosed MCL Patients, Results of a Multicenter Phase II HOVON Study

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 339-339 ◽  
Author(s):  
Jeanette K Doorduijn ◽  
Monique C. Minnema ◽  
Marie Jose Kersten ◽  
Pieternella J Lugtenburg ◽  
Martin R. Schipperus ◽  
...  
Keyword(s):  
Stem Cell ◽  
Maintenance Therapy ◽  
Phase Ii ◽  
Research Funding ◽  
Progressive Disease ◽  
Induction Treatment ◽  
High Dose ◽  
Newly Diagnosed ◽  
Grade 3

Abstract Introduction. The standard first-line treatment of young and fit mantle cell lymphoma (MCL) patients consists of a rituximab containing induction of CHOP and high dose ARA-C, followed by high dose consolidation and autologous stem cell transplant (ASCT). Thus far, almost all patients relapse after ASCT. Bortezomib is a proteasome inhibitor with activity in MCL. We investigated in a randomized phase II study whether there was any indication that maintenance therapy with bortezomib after ASCT could improve the outcome of treatment, measured as event free survival (EFS). Methods. Patients 18-65 years with newly diagnosed MCL were treated with 3 cycles of R-CHOP and 2 cycles of ARA-C (2 x 2 g/m2 iv d1-4) and rituximab (375 mg/m2, iv d11). Patients in PR or CR continued with ASCT after BEAM conditioning. Patients with a PR or CR after ASCT, with a neutrophil count > 0.5 x 109/l and platelets > 80 x 109/l were randomized between bortezomib and no further treatment. Bortezomib 1.3 mg/m2 iv was given once every two weeks, for 2 years, starting between 6 - 12 weeks after transplantation. Results . Between October 2007 and February 2012, 140 patients aged 34-66 years (median 57) were registered. Five patients were not eligible. The MIPI score was low, intermediate, high or unknown in 57%, 32%, 10% and 1% respectively. All eligible patients started induction treatment with R-CHOP. Two patients did not receive the first ARA-C cycle, because of progressive disease and physician decision. Hundred-fifteen patients (85%) received the BEAM and ASCT. Reasons to stop protocol treatment before ASCT were: progressive disease (PD) (n=6), inadequate stem cell harvest (n=3), excessive toxicity (n=3), other reasons (n=8). The response after ASCT was CR/CRu in 99 patients (86%), PR in 15 (13%), unknown in 1 (1%). Only 62 patients (45%), aged 34-65 years (median 56) were randomized between bortezomib maintenance and no further treatment. Two patients were randomized, but not eligible. Reasons for no randomization were: not eligible (n=30), patient refusal (n=14), excessive toxicity (n=2, and other reasons (n=7). In each treatment arm 30 patients were included. The patient characteristics were well balanced, except the MIPI score. In the no maintenance arm 21 patients (70%) had a low MIPI, compared to 15 patients (50%) in the bortezomib arm, and 6 (20%) versus 11 (37%) patients had an intermediate MIPI score. In both arms 3 patients (10%) had a high MIPI. Fifteen patients (50%) in the maintenance group continued bortezomib for 2 years. Reasons to stop earlier were excessive toxicity (n=6), PD/relapse (n=4), patients refusal (n=3) and other (n=2). The main adverse events during maintenance therapy were neurologic (CTC grade 2: 14%, grade 3: 4%), and infectious (grade 2: 11%, grade 3: 7%). Three patients developed a secondary malignancy: a basal cell carcinoma in the no maintenance group, a melanoma and a prostate carcinoma in the bortezomib group. With a median follow-up of the patients still alive of 50.9 months EFS at 4 years for all patients is 61%, and the overall survival (OS) 78%. The median follow-up of the randomized patients still alive is 42.9 months. The EFS at 4 years is 72% without maintenance versus 71% in the patients randomized for bortezomib maintenance. The OS at 4 years also shows no significant difference between the groups, 90% versus 93% respectively. Conclusion. There is no indication that bortezomib iv maintenance in a frequency of once every 2 weeks does improve the EFS of newly diagnosed MCL patients after intensive induction treatment with R-CHOP, double ARA-C and BEAM followed by ASCT. Figure 1. Figure 1. Figure 2. Figure 2. Disclosures Doorduijn: Celgene: Consultancy; Janssen: Consultancy; Roche: Consultancy. Off Label Use: bortezomib maintenance in MCL. Minnema:Celgene: Consultancy; Jansen Cilag: Consultancy; Amgen: Consultancy. Kersten:janssen: Honoraria, Research Funding; takeda millennium: Research Funding; roche: Honoraria, Research Funding. Lugtenburg:Mundipharma: Consultancy; Servier: Consultancy; Janssen-Cilag: Consultancy; Celgene: Consultancy; Roche: Consultancy. Schipperus:Novartis: Consultancy. Zijlstra:Celgene: Consultancy; Roche: Consultancy.

Interim Analysis of a Multicenter Trial of High Dose (HD) Imatinib in Newly Diagnosed Early Chronic Phase (CP) Patients (pt) with Chronic Myeloid Leukemia (CML).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1085-1085 ◽  
Author(s):  
Jorge Cortes ◽  
Francis Giles ◽  
August J. Salvado ◽  
Karen McDougall ◽  
Jerald Radich ◽  
...  
Keyword(s):  
Interim Analysis ◽  
Mutational Analysis ◽  
Dose Intensity ◽  
High Dose ◽  
Molecular Response ◽  
Newly Diagnosed ◽  
Entire Treatment Period ◽  
Log Reduction ◽  
One Year

Abstract While imatinib (400 mg daily) results in 12 mo complete cytogenetic responses (CCyR) in 76% of pt, complete molecular responses (CMR) at this time are in the range of 4–6%. A single center study recently showed higher 12 mo CMR when newly diagnosed CP pt were given 800 mg daily. We report here an interim analysis of similar patients treated in a Phase II single arm multicenter setting with 800 mg imatinib daily. Eligible pt. were ≥18y, had normal organ function and were newly diagnosed. Prior hydroxyurea or imatinib was allowed for ≤ 1 mo. Treatment dose was adjusted for ≥Gr3 toxicity. Peripheral blood (PB) PCR and FISH were measured every 3 mo in a central laboratory (Quest, Northridge, CA) and marrow cytogenetics and PCR was done at 1 yr in the same laboratory. The primary endpoint was molecular response at one year. Secondary endpoints included hematologic response, marrow cytogenetic response at 1 yr, progression/loss of response and safety. Accrual of 115 pt in 29 institutions was completed in April 2005 and the current report is based on 20 pt reaching 12 mo follow up by May 2005. Median follow up is 5 mo (0.2–16 mo). Median age is 51 (19–81). Sokal classification was predominantly low (73.1%) or intermediate (17.3%). To date, 11/115 patients have gone off study (4 withdrew, 4 AEs, 2 progression, 1 protocol violation). The 2 early progressing patients were withdrawn following 10 and 11 mo of treatment respectively. PB PCR showed an initial decline in both patients with a subsequent rise after 3 and 6 months respectively. Mutational analysis in these patients showed wild type (wt) bcr/abl in one and an E255V mutation identified at 6 mo in the second. Median Dose Intensity for the entire population is 98% (29–100%). By 6 mo, 24/52 pt (46%) already had a BCR-ABL/ABL ratio <0.045% (>3 log reduction from baseline). Sixteen of twenty pt (80%) have CCyR at one year with 11/20 (55%) showing non detectable levels of transcripts. The 5 pt with CCyR still showing detectable BCR-ABL/ABL ratios have a mean reduction of 3.21 (2.54–4.47) log from baseline. Two pt with MCyR have 3–15% Ph+ cells in marrow with PB FISH that is either negative or marginally positive (1.2%). PCR in these patients at 12 mo shows a 3.28 and 2.24 log reduction below the median baseline respectively. Two additional pt at 12 mo continue to have 40 and 95% PH+ metaphases in their marrow and 7% FISH positive cells in PB of both. PCR at 12 mo for these pt shows a < 2 log reduction of BCR-ABL/ABL ratio from baseline for both. Additional mutational analysis is being performed. We conclude that 800 mg daily of imatinib results in a high rate of CMR for newly diagnosed pt by 12 mo of treatment. The treatment was relatively well tolerated and could be delivered in a multicenter setting with sustained dose intensity over the entire treatment period.

Initial Results of US Intergroup Trial of Response-Adapted Chemotherapy or Chemotherapy/Radiation Therapy Based on PET for Non-Bulky Stage I and II Hodgkin Lymphoma (HL) (CALGB/Alliance 50604)

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 578-578 ◽  
Author(s):  
David J. Straus ◽  
Brandelyn Pitcher ◽  
Lale Kostakoglu ◽  
John C Grecula ◽  
Eric D. Hsi ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Research Funding ◽  
Stage I ◽  
Newly Diagnosed ◽  
Oncology Group ◽  
Interim Pet ◽  
Clinical Interest ◽  
Grade 3 ◽  
Relapse Rates

Abstract Introduction Interim positron-emission tomography (PET) following 1-3 cycles of doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) in newly-diagnosed, non-bulky stage I and II HL patients (pts) is a useful biomarker that predicts relapse rates of ≤10% for PET- pts. Relapse rates are higher in pts who are PET+ (J Clin Oncol 2014 32: 2705-11; N Engl J Med 2015 372: 1598-607). Interim PET thus provides an opportunity to minimize treatment for the majority of pts who are interim PET - and only intensify treatment for those who are PET+. This strategy could reduce short and long term treatment toxicity for the majority of pts. To test this hypothesis, the US Intergroup conducted a phase II clinical trial, CALGB/Alliance 50604, for newly-diagnosed non-bulky stage I and II HL pts. Methods Between 5/15/10 and 5/4/12, 164 previously untreated pts with non-bulky stages I/II HL were enrolled. Pts received 2 cycles of ABVD followed by PET. Deauville scores 1-3 were negative (≤ liver uptake), while scores of 4-5 were positive, based on central review. PET- pts received 2 more cycles of ABVD, and PET+ pts received 2 cycles of dose-intense bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine and prednisone (escalated BEACOPP) + 3060 cGy involved-field radiation therapy (IF RT). Prophylactic growth factor use was permitted only after grade 3/4 febrile neutropenic events, with or without infection. Results Median age was 31 years (18-58). There were 88 males and 76 females. Pt. stages were IA (16), IB (4), IIA (90), IIB (35), IIAE 4, and IIBE (3). All pts were PET+ prior to treatment. 144/164 patients had cycle 2 PET and adequate follow-up for assessment: 131 (91%) were PET- and 13 (9%) PET+. Of 20 not analyzed, 13 were excluded (6 never treated and 2 treated with < 2 cycles) and 7 had insufficient follow up. At a median follow-up time of 2 years, 8/131 (6%) PET- pts relapsed or progressed with an estimated 3-year progression-free-survival (PFS) of 92%. 4/13 (31%) PET+ pts. failed (3 relapsed, 1 suicide) with an estimated 3-year PFS of 66%. By Cox model, observed hazard ratio comparing PET- and PET+ PFS for pts is 6.04 (1.82, 20.08). It is likely that the trial will meet the primary objective of 3-year PFS of at least 85% (79%, 92%) for PET- pts treated with 2 additional cycles of ABVD. It is unlikely that the results will meet secondary objective of improving the 3-year PFS of PET+ pts treated with 2 cycles of escalated BEACOPP + IF RT to the pre-set level considered to be of clinical interest in comparison with PET- pts treated with 2 additional cycles of ABVD (HR< 3.84). There was 1 death (suicide). Toxicity for all pts was minimal: Neutropenia: 29% grade 3 and 42% grade 4; Febrile neutropenia: 5% grade 3; Decreased CO diffusing capacity: 1% grade 3; Decreased left ventricular ejection fraction: 1% grade 3; Sensory neuropathy: 2% grade 3 and 1% grade 4; Motor neuropathy: 1% grade 4. Conclusions These early results confirm interim PET as a potential biomarker for prediction of relapse with ABVD in patients with non-bulky, stages I/II HL. Importantly, this study demonstrates that defining PET- as Deauville scores of 1-3 results in only 9% of pts. remaining PET+ after 2 ABVD cycles and excellent PFS for the PET-majority. More intensive treatment with 2 cycles of escalated BEACOPP and IF RT for the 9% of pts who are interim PET+ will be unlikely to improve 3-year PFS to the level considered to be of clinical interest in this trial. Interpretation may be limited by small numbers and lack of randomized control comparison. Fortunately, exciting new treatment approaches may provide an opportunity to improve outcomes for the minority of interim PET+ pts in the future. Kaplan Meier Plot of PFS for PET-negative and PET-positive patients For Alliance for Clinical Trials in Oncology, Eastern Cooperative Oncology Group, and Southwest Oncology Group; Supported in part by U10CA180821, U10CA180820, and U10CA180888 Figure 1. Figure 1. Disclosures Straus: Millenium Pharmaceuticals: Research Funding. Hsi:Abbvie: Research Funding; Cellerent Therapeutics: Research Funding; Eli Lilly: Research Funding; Onyx: Honoraria; Seattle Genetics: Honoraria. Kahl:Roche/Genentech: Consultancy; Seattle Genetics: Consultancy; Millennium: Consultancy; Cell Therapeutics: Consultancy; Celgene: Consultancy; Infinity: Consultancy; Pharmacyclics: Consultancy; Juno: Consultancy. Cheson:Gilead: Consultancy, Research Funding; Teva: Research Funding; Celgene: Consultancy, Research Funding; Ascenta: Research Funding; Astellas: Consultancy; Pharmacyclics: Consultancy, Research Funding; Spectrum: Consultancy; AstraZeneca: Consultancy; Roche/Genentech: Consultancy, Research Funding; MedImmune: Research Funding. Bartlett:Janssen: Research Funding; Pharmacyclics: Research Funding; Astra Zeneca: Research Funding; ImaginAB: Research Funding; Genentech: Research Funding; Pfizer: Research Funding; Novartis: Research Funding; Medimmune: Research Funding; Millenium: Research Funding; Celgene: Research Funding; Gilead: Consultancy; Seattle Genetics: Consultancy, Research Funding.

Evaluation of Single Agent Lenalidomide in Patients with Newly Diagnosed Multiple Myeloma (NDMM).

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3868-3868
Author(s):  
Rachid Baz ◽  
Mohamad Hussein ◽  
Daniel J. Lebovic ◽  
Elizabeth Finley-Oliver ◽  
Mehul P Patel ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Median Time ◽  
Light Chain ◽  
Single Agent ◽  
Immunomodulatory Activity ◽  
High Dose ◽  
Newly Diagnosed ◽  
Antitumor Effects ◽  
Grade 3

Abstract Abstract 3868 Poster Board III-804 Introduction Lenalidomide (Len) is an immunomodulatory drug with antitumor effects mediated through activation of T and NK cells as well as modulation of tumor cytokine environment. Currently Len is approved in combination with dexamethasone (dex) for treatment of patients with relapsed myeloma. Interestingly, in NDMM, higher 1 and 2 year survival rates were observed when the dose of dex was reduced compared to standard high dose dexamethasone and Len (Rajkumar et al. 2008). The immune suppressive effects of dex can antagonize Len immunomodulatory activity and may explain this observation. To our knowledge, Len has not been evaluated as a single agent in NDMM. Patients and methods Records of patients with newly diagnosed symptomatic multiple myeloma treated with single agent Len at H. Lee Moffitt Cancer Center and Roswell Park Cancer Institute were reviewed (after IRB approval at both institutions). Data was collected on disease characteristics, demographics and treatment outcomes. Responses assessed as per the IMWG criteria. Results From March 2007 to July of 2009, 18 patients with NDMM have been treated with Len alone. The median age was 70 years (range 46-84), and 12/18 were males. Heavy chain was IgG in 12 and IgA in 4 patients with 2 patients with light chain myeloma. The involved light chain was kappa in half the patients. Clinical stage of patients included stage IIIA (n=13), IIA (n=4) and IA (n=1) using the DS system whereas as per the ISS system 10, 6 and 2 has stages I, II and III respectively. Cytogenetics were not available on most patients (11); and 4 of 7 patients with available cytogenetics had deletion 13q identified by FISH. The median b2m was 2.8 mg/L (range 2.1-10.7) with >3.5mg/L in 7/18 patients. All except one patient (with a creatinine clearance of 49 ml/min) were started on Len 25 mg daily for 21 days of a 28 days cycle. As of August 1st 2009, 3 patients are inevaluable for response due to short follow up. Among the remainder 15 patients, 3 achieved a CR (1 stringent CR), 2 VGPR, 3 PR, 4 had MR with SD in additional 3 patients. Thus MR or better response was noted in 80% of patients. The median time to first response was 55 days (range 28-98) and median time to best response was 73 days (range 31-591). After a median follow up of 7 months (range 1-26), 1 patient died of progressive disease (despite the addition of dexamethasone and subsequent bortezomib therapy), 4 patients required the addition of dexamethasone. Len was generally well tolerated and no grade 4 hematologic toxicity were noted, 1 patient had grade 3 neutropenia, 1 patients grade 3 anemia and 2 patient grade 3 thrombocytopenia. Four patients had Len dose reduced. Conclusion Single agent Len appears to be an effective therapy in newly diagnosed myeloma patients (MR and better in 80% of patients) and should be evaluated in a prospective fashion in an attempt to decrease corticosteroid toxicity in a group of vulnerable patients and potentially enhance the immunomodulatory activity of Len. Our experience suggests that single agent Len can be effectively employed as an initial step in sequencing anti-myeloma regimen(s) for treatment of NDMM. Disclosures: Baz: celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding. Off Label Use: lenalidomide as a single agent in newly diagnosed myeloma. Hussein:Celgene: Employment.

Safety and disease control achieved with the addition of nivolumab (Nivo) to chemoradiotherapy (CRT) for intermediate (IR) and high-risk (HR) local-regionally advanced head and neck squamous cell carcinoma (HNSCC): RTOG Foundation 3504.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 6073-6073 ◽  
Author(s):  
Maura L. Gillison ◽  
Robert L. Ferris ◽  
Jonathan Harris ◽  
A. Dimitrios Colevas ◽  
Loren K. Mell ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Performance Status ◽  
High Dose ◽  
Newly Diagnosed ◽  
Programmed Death ◽  
Platinum Refractory ◽  
Programmed Death 1 ◽  
Grade 3 ◽  
Clinical Trial Information

6073 Background: Nivo, which inhibits the programmed death-1 (PD-1) receptor, improved survival for pts with platinum-refractory recurrent/metastatic HNSCC. A clinical trial evaluated the safety of adding nivo to 4 standard intensity modulated (chemo) radiotherapy (RT) regimens (see table) for pts with newly diagnosed IR/HR HNSCC. Primary endpoint was safety and feasibility. Methods: Eligibility included IR (p16+ oropharynx [op], T1-2N2b-N3/T3-4N0-3, >10 pack-years [pys], or T4N0-N3/T1-3N3, ≤10 pys) & HR HNSCC (oral cavity, larynx, hypopharynx, p16- op, T1-2N2a-N3/T3-4N0-3). 10 pts/arm (8 evaluable; 0-2/8 DLTs acceptable). Nivo (dose & schedule varied per arm) started 2 wks pre-RT & continued 3 months post-RT. Feasibility of adjuvant nivo months 3-12 post-RT defined as ≥4 of 8 pts/arm received 7 doses. Arm 4 limited to age ≥70, Zubrod performance status (PS) 2, CrCl <50 ml/min, grade ≥2 hearing loss or ≥ grade 3 neuropathy. Results: Characteristics of 39/40 treated pts: median age 62, 79% male, 49% PS0, 38% HR, 67% >10 pys, 62% p16+ op, 72% T3-4, 85% N2-3. Grade ≥3 nivo-related AEs: adrenal insufficiency, diarrhea-3, anemia, fatigue-2, mucositis-3, nausea, vomiting, lipase increase-6, amylase increase-2, lymphocyte/neutrophil/WBC decrease-4, hyponatremia-3, anorexia, maculo-papular rash. SAE in 4/10, 4/9, 5/10 & 4/10. DLTs, adjuvant chemo feasibility, median follow-up (mo), progression or death events per arm shown in table. Conclusions: Nivo concomitant with all (chemo)RT regimens was safe for patients with newly diagnosed IR/HR HNSCC but adjuvant nivo was infeasible after high-dose cisplatin or in cisplatin-ineligible patients ( NCT02764593 ). Preliminary data on progression/death is provided. Acknowledgements: Support for this study was provided by Bristol-Myers Squibb Company. Clinical trial information: NCT02764593. [Table: see text]

Retrospective Evaluation of Rituximab, Methotrexate, Procabazine, Vincristine and Etoposide Followed By Consolidation with Rituximab, Aracytine and Ifosfamide for Elderly Patients with Newly Diagnosed Primary CNS Lymphoma

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 6-7
Author(s):  
Gabriel Antherieu ◽  
Edith Julia ◽  
Emmanuelle Nicolas-Virelizier ◽  
Marie-Charlotte Laude ◽  
Violaine Safar ◽  
...  
Keyword(s):  
Board Of Directors ◽  
B Cell Lymphoma ◽  
Hematological Toxicity ◽  
High Dose ◽  
Toxicity Profile ◽  
Newly Diagnosed ◽  
Advisory Committees ◽  
Grade 3 ◽  
Favorable Toxicity Profile

Introduction Primary cerebral lymphoma (PCNSL) is an uncommon subtype of diffused large B-cell lymphoma (DLBCL) with a particular poor outcome as compared to systemic DLBCL, especially in elderly. For patients older than 60 years, standard treatment consists of high-dose methotrexate (HD-MTX) chemotherapy without consolidation brain radiotherapy to reduce the risk of leukoencephalopathy. Rituximab in combination with HD-MTX, procarbazine, vincristine followed by HD-cytarabine consolidation is one of standard of treatments for PCNSL patients with a 2-year PFS rate of 47% for patients aged of 60 or older in prospective trial (Morris JCO 2013). Etoposide and Ifosfamide are two drugs that can diffuse across blood-brain barrier and commonly used for relapsed/refractory PCNSL. To improve efficacy of R-MPVA protocol, we developed a new regimen which consisted in adding etoposide and ifosfamide for patients with a newly diagnosed PCNSL aged between 60 and 75 years old. Patients & Methods The protocol consisted of 3 cycles every 28 days of rituximab (375mg/m2, J1 and J15), MTX (3.5 g/m2, J1 and J15), vincristine (1.4 mg/m2, J1 and J15), vepeside (100mg/m2, J2) and procarbazine (100mg/m2, J1-7). Consolidation therapy consisted of 2 cycles every 21 days rituximab (375mg/m2, J1) in combination with cytarabine (3g/m2, J1-2) with ifosfamide (1.5 g/m2, J1-3). Response evaluations were planned after the 3 cycles of induction (R-MPV-VP16) and after consolidation (R-AraC-Ifo). We retrospectively reviewed treatment modalities, toxicities, response and outcome with this protocol and compared results with a matched group of patients with the same range age (60 - 75 years) treated with R-MPVA. Results Between 2013 and 2018, 28 PCNSL patients were treated with this protocol. The median age was 67.5 years old (range, 61-74). Poor performance status (PS 3-4) was presented in 9 patients (32%). As compared to 31 patients treated between 2007 and 2018 with R-MPVA, patients treated with intensive protocol were younger (66 vs. 69 years, P=0.01) and had less frequently a poor PS 3-4 (32% vs. 61%, P=0.04). In intent-to-treat analysis, 27 patients received 3 cycles of R-MPV-VP16 but one received only 2. Among them, five patients achieved PR and then received 1 to 2 additional cycles of R-MPV-VP16. Following this induction, 25 patients underwent 2 cycles R-AraC-ifo consolidation, 3 of them did not received ifosfamide for the second cycle because of hematological toxicity and poor PS. One patient in complete response (CR) after whole treatment received high-dose therapy followed by autologous stem cell transplantation. After R-MPV-VP16, 10 patients (36%) achieved CR and 14 partial responses (50%) (PR) as compared to 12 CR (39%) and 12 PR (39%) for patients treated with R-MPVA. After consolidation phase, 23 patients (82%) achieved CR after R-AraC-Ifo as compared to 21 CR (68%) after R-AraC in the historical arm. Differences were not statistically significant. R-MPV-VP16 regimen was associated with favorable toxicity profile with 13 (46%) grade 4 hematological toxicity, 8 (28%) grade 3 and one grade 4 (3%) renal toxicity, 3 (10%) grade 3 and one grade 4 (3%) hepatic toxicity, 6 (21%) grade 3 and 4 grade 4 (14%) and infectious toxicity. With a median follow-up of 46.5 months, patients treated with R-MPV-VP16 followed by R-AraC-ifo had a median event-free survival (EFS) of 33.2 months (95%CI, 17.6 - not reached [NR]) with a 2-year EFS rate of 52%; the median overall survival (OS) was not reached (95%CI, 58.6-NR) with a 2-year OS rate of 70%. With a median follow-up of 94.2 months, patients treated with R-MPVA had a median EFS of 18.3 months with a 2-year EFS rate of 39% (P=0.14, Fig 1); the median OS was 65.9 months with 2-year OS rate of 64% (P=0.33, Fig 1). Conclusions In this retrospective analysis of two HD-MTX and HD-AraC based regimens for PCNSL patients aged between 60 and 75 years performed in real-life setting, R-MPVA was more frequently proposed for older patients with a poorer PS. Combination of vepeside to R-MPV and ifosfamide to R-AraC was feasible with a favorable toxicity profile. Despite not statistically different, we observed a trend for an improvement of response rate at the end of treatment (82% vs. 68% of CR) and reduced rate of relapses (2-year EFS rates: 52% vs. 39%) with the intensified protocol. These first results deserve a confirmative larger prospective study of R-MPV-VP16 followed by R-AraC-ifosfamide for elderly PCNSL patients. Disclosures Ferrant: AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees. Karlin:Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, personal fees; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, personal fees; Celgene: Other: Personal fees; Sanofi: Honoraria; GlaxoSmithKline: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, personal fees; Celgene/Bristol-Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support. Bachy:Beigene: Membership on an entity's Board of Directors or advisory committees; Roche, Celgene, Amgen, Janssen, Gilead, Novartis, Sanofi: Honoraria; Amgen: Research Funding; Roche, Gilead: Consultancy.

Dose-intensive chemotherapy with ifosfamide, epirubicin, and filgrastim for adult patients with metastatic or locally advanced soft tissue sarcoma: a phase II study.

1998 ◽  
Vol 16 (4) ◽  
pp. 1438-1443 ◽  
Author(s):  
P Reichardt ◽  
J Tilgner ◽  
P Hohenberger ◽  
B Dörken
Keyword(s):  
Soft Tissue ◽  
Continuous Infusion ◽  
Locally Advanced ◽  
Soft Tissue Sarcomas ◽  
High Dose ◽  
Impact On Survival ◽  
Grade 3 ◽  
Stimulating Factor ◽  
Experienced Grade

PURPOSE To evaluate the feasibility and toxicity of the combination of full-dose epirubicin (EPI) and high-dose ifosfamide (IFO) with granulocyte colony-stimulating factor (G-CSF) support and to determine the clinical efficacy in terms of response and impact on survival. PATIENTS AND METHODS Forty-six consecutive, previously untreated patients with locally advanced or metastatic high-grade soft tissue sarcomas were treated with IFO 2.5 g/m2/d as a continuous infusion on days 1 to 5 and EPI 45 mg/m2/d as a continuous infusion on days 2 and 3 every 3 weeks. G-CSF 5 microg/kg/d subcutaneously (s.c.) was given on days 6 to 15 or until recovery of leukocytes after all cycles. Response evaluation was performed every two cycles and responding patients were treated with up to six cycles. All patients were evaluated for resectability of residual local or metastatic disease and underwent surgery if possible. RESULTS All patients experienced grade 3 or 4 myelosuppression. Other toxicities were mild. The overall response rate was 52%, with a complete remission (CR) rate of 22% after chemotherapy alone. Eight additional patients were rendered free of tumor (no evidence of disease [NED]) by surgical procedures. The median overall survival of all patients is 24 months. The CR/NED patients (39%) have a significantly superior survival time compared with all other patients. Thirteen of these 18 patients (72%) are alive, nine free of tumor, with a median follow-up time of 33 months. CONCLUSION This dose-intensive combination chemotherapy is toxic but feasible and produced a high number of partial remissions (PRs) and especially CRs, which resulted in prolonged survival.

A Randomized Trial of Lenalidomide Plus High-Dose Dexamethasone (RD) Versus Lenalidomide Plus Low-Dose Dexamethasone (Rd) in Newly Diagnosed Multiple Myeloma (E4A03): A Trial Coordinated by the Eastern Cooperative Oncology Group.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 74-74 ◽  
Author(s):  
S. Vincent Rajkumar ◽  
Susanna Jacobus ◽  
Natalie Callander ◽  
Rafael Fonseca ◽  
David Vesole ◽  
...  
Keyword(s):  
Disease Progression ◽  
Low Dose ◽  
Response Rate ◽  
Phase Iii ◽  
High Dose ◽  
Type I ◽  
Newly Diagnosed ◽  
High Dose Dexamethasone ◽  
Grade 3 ◽  
One Year

Abstract Aim: A phase III trial of lenalidomide plus high (standard) dose dex (RD) versus lenalidomide plus low dose dex (Rd) in newly diagnosed myeloma (MM). Methods: Pts with untreated, symptomatic MM were eligible. Pts in the RD arm (Arm A) received lenalidomide 25 mg/day PO days 1–21 every 28 days plus dex 40 mg days 1–4, 9–12, and 17–20 PO every 28 days; pts in the Rd arm (Arm B) received lenalidomide at the same dose plus dex 40 mg days 1, 8, 15, and 22 PO every 28 days. The primary endpoint was response rate at 4 months, with the null hypothesis being that the response rates in the two 2 arms are equivalent. Planned sample size was 196 eligible pts per arm with one-sided 0.10 Type I and 0.05 Type II error rate. All analysis were performed on an intent to treat basis. An independent DMC recommended release of study results. Results: 445 pts (median age, 65 yrs) were accrued; 223 randomized to RD, 222 to Rd. Median follow-up time is 17 months. Arms were well balanced for age, gender, stage, bone lesions, hemoglobin, beta-2 microglobulin, performance status, bone marrow plasma cells, and M protein levels at baseline. Major grade 3 or higher toxicities, including DVT/PE and infections, were significantly higher in the high dose dex arm (see Table). Overall survival (OS) at the second pre-planned interim analysis was significantly superior with lenalidomide plus low dose dex, P<0.001; one year survival 96% (Rd) versus 87% (RD). The 18 month survival rate is 91% versus 80%, respectively. OS differences in favor of the low dose dex arm were seen in pts <65 (P=0.022; one year rate 97% vs 92%) as well as pts 65 and older (P=0.002; one year rate 94% vs 83%), respectively. Sixty-one patients have died; 42 in the RD arm and 16 in Rd arm. The cause of death has been verified by detailed chart review in 38 patients. Of 29 verified deaths in the RD arm, 13 were due to disease progression, 6 thrombosis/embolism, 3 infection, 3 cardiac ischemia, 1 stroke, and 1 respiratory failure. Of 9 verified deaths in the Rd arm, 5 were due to disease progression, 2 infection, 1 thrombosis/embolism, and 1 cardiac arrest. Response rate data are expected to be available at the time of the meeting. Conclusions: Lenalidomide plus low-dose dexamethasone (Rd) is associated with superior OS compared to lenalidomide plus high-dose dexamethasone (RD) in newly diagnosed MM. The increased mortality in Arm A is due to disease progression (myeloma deaths) as well as increased toxicity. This study has major implications for the use of high-dose dexamethasone in the treatment of newly diagnosed MM. Major Grade 3 or Higher Adverse Events Toxicity Arm A % Arm B % P value Neutropenia 10 19 0.01 DVT/PE 25 9 <0.001 Infections 16 6 <0.001 Any grade 3 or higher non-hematologic 49 32 <0.001 Any grade 4 or higher non-hematologic 20 9 <0.001 Deaths in first 4 months 5 0.5 0.006

Early Optimization of Imatinib Therapy in Patients Newly Diagnosed with Chronic-Phase Chronic Myeloid Leukemia (CP-CML). A Study of the Spanish PETHEMA Group.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1113-1113
Author(s):  
Francisco Cervantes ◽  
Pilar López-Garrido ◽  
María-Isabel Montero ◽  
Fermín Jonte ◽  
Jesus Martinez ◽  
...  
Keyword(s):  
Chronic Phase ◽  
Cytogenetic Response ◽  
Hematological Toxicity ◽  
Molecular Response ◽  
Newly Diagnosed ◽  
Intention To Treat ◽  
Number Of Patients ◽  
Grade 3 ◽  
One Year

Abstract Abstract 1113 Poster Board I-135 Currently, imatinib (IM) 400 mg daily is the frontline therapy for patients with CP-CML. In an attempt to improve the therapeutic response to IM, the Spanish collaborative PETHEMA group undertook a study of early optimization of therapy, in which 210 adult patients newly diagnosed with CP-CML (< 3 months from diagnosis) were included. Median age was 44 (range: 18-71) years and distribution by Sokal groups: low risk 56%, intermediate risk 28%, and high risk 16%. Hydroxyurea was permitted before IM. Patients initially received IM 400 mg daily for 3 months and then those failing to achieve a complete hematologic response (CHR) had the dose increased (to 600 and then 800 mg daily), while the remainder were maintained on 400 mg daily for three more months. At 6 months, depending on cytogenetic response, patients were kept on IM 400, if they had achieved a complete cytogenetic response (CCyR), or randomized to receive higher IM doses (600 and then 800 mg) or IM 400 plus low dose interferon (IFN, 3 million units 3 times a week) in case that a CCyR had not been attained by that time. In patients already in CCyR at 6 months, the IM dose was increased if a major molecular response (MMolR) according to the international scale had not been achieved at 18 months, whereas in patients not in CCyR and randomized at 6 months, a switch to a second generation TKI (dasatinib or nilotinib) was permitted if a CCyR was not achieved at one year of randomization. At standard intervals, cytogenetic response was assessed in bone marrow by chromosome banding analysis and molecular response determined in peripheral blood by RT-Q-PCR performed in three reference laboratories. At the time of the analysis, median follow-up was 48.3 (range: 1.2-73) months. Median time from diagnosis to IM start was 0.5 (range: 0-2.8) months; 72% of patients started IM within one month from diagnosis. At 3 months of treatment, 4 patients had not achieved a CHR; two of them failed to achieve a favorable response following the increase in the IM dose. At 6 months, a CCyR was obtained in 79% of patients; of the 41 patients not in CCyR, 9 could not be randomized because of toxicity (n= 3) or withdrawal of consent (n=6), 17 were assigned to higher IM dose, and 15 to IM 400 + IFN, but only 9 of the latter actually started IFN. Due to the scarce number of patients randomized, no comparison could be established between the two arms. Overall, cumulative incidence of response at 3 years was: CHR 98.6%, CCyR 90%, and MMolR 82%. Based on an intention-to-treat analysis, CCyR was 70% at 18 months. With current follow-up, only 5 patients have died and 9 have progressed to the accelerated or blastic phases (AP/BP). At 5 years, overall survival rate is 97.5%, survival free from AP/BP 95.5%, survival free from failure (including death, progression to AP/BP and the lack of achievement or the loss of a previously obtained CHR and CCyR) 82%, and event-free survival (including the above plus the permanent IM discontinuation for any reason) 80%. Twenty-seven patients (12.8% of the overall group) had grade 3-4 hematological toxicity and 26 (12.4%) grade 3-4 nonhematological side effects, in most cases during the first year of treatment. The presentresults show the benefit of prompt institution and early optimization of IM therapy in patients with newly diagnosed CP-CML. Disclosures Cervantes: Novartis: Consultancy, Speakers Bureau; Bristol-Myers Squibb: Consultancy, Speakers Bureau.

Sign in / Sign up

Export Citation Format

Share Document