scholarly journals Delivering HDAC over 3 or 5 days as consolidation in AML impacts health care resource consumption but not outcome

2020 ◽  
Vol 4 (16) ◽  
pp. 3840-3849 ◽  
Author(s):  
Pierre-Yves Dumas ◽  
Sarah Bertoli ◽  
Emilie Bérard ◽  
Thibaut Leguay ◽  
Suzanne Tavitian ◽  
...  
Keyword(s):  
Health Care ◽  
Residual Disease ◽  
Total Duration ◽  
Length Of Hospital Stay ◽  
Standard Of Care ◽  
Complete Response ◽  
Health Care Resource ◽  
Resource Consumption ◽  
High Dose ◽  
Treatment Regimens

Abstract Postremission treatment is crucial to prevent relapse in acute myeloid leukemia (AML). High-dose cytarabine delivered every 12 hours on days 1, 3, and 5 (HDAC-135) is the standard of care for younger adult patients with AML. Although this standard has been unsuccessfully challenged by other treatment regimens, including multiagent chemotherapy, the timing of HDAC administration has attracted little attention. Here, we retrospectively compared the safety, efficacy, and health care resource consumption associated with HDAC-135 and another standard, condensed HDAC-123 regimen, as consolidation treatment in younger AML patients in first complete response. This study included 221 patients (median age, 46.6 years; range, 18-60 years). HDAC-123 and HDAC-135 were used in 92 and 129 patients, respectively. Both regimens were associated with similar rates of relapse-free survival, cumulative incidence of relapse, nonrelapse mortality, and overall survival, including in core binding factor AML subgroup in which levels of minimal residual disease reduction were similar in both schedules. Hematological recovery times regarding neutrophils and platelets were significantly shorter in patients receiving HDAC-123, with an average difference of 3 to 4 days for each consolidation cycle. The total duration of hospitalization for the whole postremission program was shorter with HDAC-123 (32 days; interquartile ratio [IQR], 22.0,36.5) compared with HDAC-135 (41 days; IQR, 30.5, 50.0) (P < .0001). In conclusion, the condensed HDAC-123 regimen induced faster hematological recovery and therefore significantly reduced the length of hospital stay without affecting treatment response or outcome in younger AML patients.

Stem cell (SC) yield and transplantation results from transplant-eligible newly diagnosed multiple myeloma (TE NDMM) patients (pts) receiving daratumumab (DARA) + bortezomib/thalidomide/dexamethasone (D-VTd) in the phase 3 CASSIOPEIA study.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 8042-8042 ◽  
Author(s):  
Cyrille Hulin ◽  
Philippe Moreau ◽  
Michel Attal ◽  
Karim Belhadj ◽  
Lotfi Benboubker ◽  
...  
Keyword(s):  
Stem Cell ◽  
Residual Disease ◽  
Standard Of Care ◽  
Complete Response ◽  
Median Number ◽  
High Dose ◽  
Phase 3 ◽  
Hematopoietic Reconstitution ◽  
Risk Of Progression ◽  
Successful Transplantation

8042 Background: High-dose therapy (HDT) followed by autologous stem-cell transplantation (ASCT) is the standard of care in TE NDMM. In the phase 3 CASSIOPEIA study, D-VTd significantly improved stringent complete response (sCR), ≥CR, and minimal residual disease (MRD)-negative rates and reduced the risk of progression/death vs VTd in TE NDMM pts. We assessed SC yield and transplantation results among pts receiving D-VTd vs VTd induction prior to HDT/ASCT in Part 1 of CASSIOPEIA. Methods: In Part 1, TE NDMM pts ages 18-65 y were randomized 1:1 to 4 pre-transplant induction and 2 post-transplant consolidation cycles of DARA + VTd or VTd alone. After induction, pts underwent SC mobilization with cyclophosphamide 3 g/m2 (recommended dose) and GCSF. Peripheral blood SCs were harvested based on response to mobilization. Plerixafor was given if SC collection failed at first attempt and in accordance with institutional practice. Melphalan 200 mg/m2 IV was given as HDT prior to ASCT. Results: A total of 1085 pts were randomized (D-VTd, 543; VTd, 542). Among pts who completed mobilization (D-VTd, 506; VTd, 492), more pts receiving D-VTd vs VTd received plerixafor during mobilization (21.7% vs 7.9%). Pts underwent a median (range) of 2 (1-6) vs 1 (1-4) days of apheresis for D-VTd vs VTd. The median number of CD34+ cells collected was lower for D-VTd vs VTd (6.3×106/kg vs 8.9×106/kg). Nevertheless, a similar percentage of ITT pts receiving D-VTd vs VTd underwent ASCT (90.1% vs 89.3%). The median number of CD34+ cells transplanted for D-VTd vs VTd was 3.3×106/kg vs 4.3×106/kg. Hematopoietic reconstitution rates were high and similar for transplanted pts receiving D-VTd vs VTd (99.8% vs 99.6%). For D-VTd vs VTd, a median (range) of 13.0 (6-54) vs 13.0 (4-43) days was required to achieve sustained ANC > 500 cells/mm3, and a median (range) of 14.0 (2-56) vs 12.0 (1-47) days was required to achieve sustained platelets > 20,000 cells/mm3 without transfusion. Conclusions: SC mobilization and collection was feasible with D-VTd induction. Adding DARA to VTd allowed successful transplantation in pts with TE NDMM. Clinical trial information: NCT02541383.

A Pilot Study of Acalabrutinib with Bendamustine/Rituximab Followed By Cytarabine/Rituximab (R-ABC) for Untreated Mantle Cell Lymphoma

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 8-9
Author(s):  
Daniel Guy ◽  
Marcus Watkins ◽  
Fei Wan ◽  
Nancy L. Bartlett ◽  
Amanda F Cashen ◽  
...  
Keyword(s):  
Stem Cell ◽  
Board Of Directors ◽  
Research Funding ◽  
Residual Disease ◽  
Complete Response ◽  
High Dose ◽  
Advisory Committees ◽  
Mantle Cell ◽  
Grade 3 ◽  
Stem Cell Collection

Introduction The management of younger fit patients with mantle cell lymphoma (MCL) varies widely with no consensus on an optimal induction therapy. To date, the treatments with the longest progression-free survival incorporate a chemotherapy backbone that includes high dose cytarabine, followed by consolidation with an autologous stem-cell transplantation (ASCT) (Hermine et al. Lancet 2016, Eskelund et al. Br J Haematol 2016). Recent data showed that a regimen of bendamustine/rituximab followed by cytarabine/rituximab achieved high complete response rates with high minimal residual disease (MRD) negativity (Merryman RW et al. Blood Adv 2020). We hypothesized that adding the Bruton tyrosine kinase inhibitor acalabrutinib to the same chemotherapeutic backbone would be safe and increase complete response rates as well as minimal residual disease (MRD) negativity pre-transplant, and potentially improve clinical outcomes. Methods We conducted a single arm, single institution pilot study registered at clinicaltrials.gov (NCT03623373). Patients with untreated MCL, who were between ages 18-70 and were candidates for ASCT, were eligible. Patients received six 28-day cycles of treatment. Cycles 1-3 consisted of bendamustine 90 mg/m2 on days 1 and 2, rituximab 375 mg/m2 on day 1 and acalabrutinib 100mg BID on days 1 through 28. Cycles 4-6 consisted of rituximab 375 mg/m2 on day 1, cytarabine 2 g/m2 (1.5 g/m2 if age>60) q12 hours on days 1 and 2, and acalabrutinib 100mg BID on days 1 through 7 and 22 through 28. Restaging PET/CT and response assessment based on the Lugano classification were obtained following cycles 3 and 6. After cycle 6 patients underwent leukapheresis and stem-cell collection as preparation for ASCT. Blood for MRD status was collected after cycles 2, 4 and 6 and will be evaluated using the ClonoSeq assay (Adaptive Biotechnologies). The primary objective was to determine the stem cell mobilization success rate. Secondary objectives included safety and tolerability, overall response rate (ORR), pre-transplant complete response rate (CR), and the MRD negativity rate during and after completion of therapy. Results The trial enrolled 14 patients from December 2018 to February 2020. One patient withdrew consent prior to start of treatment and another was found to have an undiagnosed adenocarcinoma shortly after starting MCL treatment. Both are excluded from the analysis. The median age was 57 years (range 52-66). 11 patients were males (92%), all patients had an ECOG performance status of 0-1. 11 patients (92%) presented with stage IV disease. The mean MCL International Prognostic Index (MIPI) score was 6.3 (25% high-risk, 42% intermediate-risk and 33% low-risk). Of the 12 patients who began treatment, 9 completed all 6 cycles. Three patients did not complete therapy due to: insurance issues (n = 1), and thrombocytopenia (n = 2) following cycle 5 and 4. The side effect profile showed expected hematologic toxicities with grade 3-4 cytopenias in all patients, mostly during cytarabine cycles. In total, 100% of patients developed grade 3-4 thrombocytopenia and 83% of patients developed grade 3-4 neutropenia. Three episodes of febrile neutropenia were observed. One patient had a grade 3 transaminase increase, and one patient had grade 3 diarrhea. No bleeding events or treatment related deaths occurred. The remainder of the side effects were low grade and the treatment was generally well tolerated. Of the 12 evaluable patients, 10 responded (ORR 83%) with 9 achieving CR (75%). One patient achieved PR prior to being removed from the study due to thrombocytopenia and then achieved CR off study. Two patients experienced PD during induction. With a median follow up of 9 months, no responding patients have relapsed. The median CD34+ stem cell collection was 3.84x106 cells/kg (range 2.77 - 5.9). MRD results will be presented at the meeting. Conclusions This is the first study attempting to combine BTK inhibition with a high dose cytarabine containing regimen. The addition of acalabrutinib to a regimen of bendamustine/rituximab followed by cytarabine/rituximab appears to be safe. The R-ABC combination will be further tested in the recently activated intergroup trial EA4181. Disclosures Bartlett: Autolus: Research Funding; BMS/Celgene: Research Funding; Forty Seven: Research Funding; Immune Design: Research Funding; Janssen: Research Funding; Kite, a Gilead Company: Research Funding; Merck: Research Funding; Millennium: Research Funding; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmacyclics: Research Funding; Seattle Genetics: Consultancy, Research Funding; Roche/Genentech: Consultancy, Research Funding; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees, Research Funding; BTG: Consultancy; Acerta: Consultancy; Affimed Therapeutics: Research Funding; ADC Therapeutics: Consultancy. Fehniger:ImmunityBio: Research Funding; HCW Biologics: Research Funding; Kiadis: Consultancy; Nkarta: Consultancy; Indapta: Consultancy; Wugen: Consultancy; Orca Biosystems: Consultancy; Compass Therapeutics: Research Funding. Ghobadi:Amgen: Consultancy, Research Funding; Kite: Consultancy, Research Funding; Bristol Myers Squibb: Consultancy; EUSA: Consultancy; WuGen: Consultancy. Mehta-Shah:Bristol Myers-Squibb: Research Funding; C4 Therapeutics: Consultancy; Celgene: Research Funding; Genetech/Roche: Research Funding; Innate Pharmaceuticals: Research Funding; Kyowa Hakko Kirin: Consultancy; Verastem: Research Funding; Karyopharm Therapeutics: Consultancy; Corvus: Research Funding. Kahl:Celgene Corporation: Consultancy; AstraZeneca Pharmaceuticals LP: Consultancy, Membership on an entity's Board of Directors or advisory committees; Genentech: Consultancy; Pharmacyclics LLC: Consultancy; Roche Laboratories Inc: Consultancy; BeiGene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Acerta: Consultancy, Research Funding; ADC Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Consultancy.

Immunoglobulin Heavy/Light Chain Measurements During Monitoring Provide Prognostic Information of Relapse After Therapy in Myeloma Patients

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3964-3964 ◽  
Author(s):  
Mark T Drayson ◽  
Oscar Berlanga ◽  
Tim Plant ◽  
Nicola J Newnham ◽  
Philip Young ◽  
...  
Keyword(s):  
Partial Response ◽  
Light Chain ◽  
Progressive Disease ◽  
Residual Disease ◽  
Complete Response ◽  
Maximum Response ◽  
High Dose ◽  
Cell Transplant ◽  
Normal Ranges ◽  
Normal Ratio

Abstract Abstract 3964 Introduction: Monitoring multiple myeloma (MM) patients is required to help guide therapy and assess response. Currently the most commonly employed tests to monitor MM patients include serum protein electrophoresis (SPEP), immunofixation (IFE), 24hr urine and serum free light chain (FLC) analysis. Whilst electrophoretic tests are adequate for IgG MM, they may be inadequate for IgA MM where the monoclonal immunoglobulin co-migrates with other serum proteins (∼60% of cases). Recently the inclusion of FLC testing to identify patients in stringent complete response (sCR) has been recommended. Novel nephelometric reagents have become available that can quantify IgA kappa and IgA lambda immunoglobulins (HLC) in serum. Here we assess the use of these tests at maximum response to detect residual disease and comment on the prognostic value of sCR. Patients, materials and methods:196 IgA MM patient samples recruited from the MRC IX trial were assessed at maximum response. Briefly, patients were randomised on to intensive (I: induction therapy with CVAD or CTD followed by high-dose melphalan and ASCT) and non-intensive (NI: clodronate or zoledronic with MP or CTDa) arms. Median age was 59 years (range: 37–71) and 74 years (range: 65–89) for patients in the I and NI arms, respectively. 31% patients in the I arm and 39% in the NI arm presented with stage III disease. Samples were taken 3 months after autologous stem cell transplant or maximum response and analysed nephelometrically using serum FLC and HLC immunoassays. Ratios for both FLC and HLC were compared to normal ranges (FLC normal ratio= 0.256–1.65, IgAkappa/IgAlambda normal ratio=0.8–2.04). Additionally, isotype-matched immunoparesis was described as <0.48 g/L IgAkappa and <0.36g/L IgAlambda. Results were compared to SPEP, IFE and total immunoglobulin assays (where immunoparesis was described as <6g/L IgG and <0.4g/L IgM). 2-year progression free survival (PFS) was determined using Kaplan Meier analysis (SPSS v 19.0). Results: 3 months post-therapy, patient responses were: I arm: progressive disease (PD): n=1(<1%); minimal response (MR): n=1(<1%); partial response (PR): n=10(8%); very good partial response (VGPR): n=35(29%); complete response (CR): n=13(11%); sCR: n=58(48%); for two patients no data was available; NI arm: progressive disease (PD): n=3(4%); stable disease (SD): n=5(7%); MR: n=10(13%); PR: n=31(41%); VGPR: n=16(21%); CR: n=11(15%). Within the 2-year follow up, 41% patients in the I arm and 46% in the NI arm relapsed. Median PFS was not significantly different between the two arms (not reached v 7 months, p=0.65). Response (3VGPR) was not associated with PFS in either arm (I, p=0.717; NI, p=0.236). By contrast, achievement of a sCR (p=0.013) was significantly associated with longer PFS in the I arm and tended towards significance in the NI arm (p=0.063). An abnormal HLC ratio was associated with shorter PFS in both arms (I, p=0.002; NI, p=0.032). In all patients achieving a 3VGPR, an abnormal HLC ratio was associated with shorter PFS (p>0.0001). Similarly, in patients achieving a 3CR an abnormal HLC ratio was also associated with shorter PFS (p=0.04). Furthermore, patients achieving a CR where both FLC and HLC ratios were normal had a significantly longer PFS than those with an abnormal FLC or HLC ratio (median PFS not reached v 18 months, p=0.007). Isotype-matched immunoparesis was associated with shorter PFS in all patients achieving a CR (p=0.061). By contrast, systemic immunoparesis of either IgG or IgM immunoglobulins were not associated with PFS (p=0.525 and p=0.964, respectively). Discussion: Novel therapies have dramatically improved MM patient outcomes, however improvements in the assessment of those outcomes has not followed a similar trajectory. Here we present data suggesting immunoglobulin HLC ratios may be better markers of residual disease than electrophoretic methods. In addition a response category based on normalisation of both FLC and HLC ratios may be more valuable than sCR. Finally, the identification of isotype matched immune reconstitution as a marker of outcome suggests a preferential suppression of immunoglobulin production not previously reported. Conclusion: Normalisation of the FLC and HLC ratio at maximum response is a better assessment of disease than IFE. Further work is required to validate these results and to assess FLC and HLC ratios against multi-parametric flow cytometry. Disclosures: Young: Binding Site: Employment.

Paradigm towards Tailored Therapies and Complete Responses in the Treatment of Metastatic Renal Cell Carcinoma

2012 ◽  
Vol 08 (01) ◽  
pp. 30
Author(s):  
Mayer Fishman ◽  
Thomas Hutson ◽  
Neeraj Agarwal ◽  
Eric Jonasch ◽  
◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Kinase Inhibitors ◽  
Mammalian Target Of Rapamycin ◽  
Interleukin 2 ◽  
Standard Of Care ◽  
Complete Response ◽  
High Dose

In recent years, the management of metastatic renal cell carcinoma (mRCC) has been revolutionized by the advent of targeted therapies. Multitargeted kinase inhibitors (such as sunitinib, sorafenib, pazopanib, and axitinib), the vascular endothelial growth factor inhibitor bevacizumab, and mammalian target of rapamycin inhibitors (such as everolimus and temsirolimus) have become the standard of care for the palliation of metastatic disease. Unfortunately, cumulative toxicities and the lack of marked benefits have prevented the combined use of most molecularly targeted agents. Selected patients with mRCC benefit from immunotherapy, as subsets of patients can experience long-term disease remission or complete response with high-dose interleukin-2. In order to optimize the value of immunotherapy, improvements in the selection of drugs and combinations with novel immunomodulatory agents must be pursued.

Health care resource utilization in patients with advanced melanoma receiving immunotherapies in the real world.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 9532-9532
Author(s):  
Richard Wayne Joseph ◽  
Alicia C. Shillington ◽  
Todd Lee ◽  
Cynthia Macahilig ◽  
Scott J. Diede ◽  
...  
Keyword(s):  
Health Care ◽  
Resource Utilization ◽  
Real World ◽  
Health Care Resource ◽  
Advanced Melanoma ◽  
The Real ◽  
Health Care Resource Utilization ◽  
Treatment Regimens ◽  
Ed Visits

9532 Background: Both pembrolizumab (PEMBRO) and combination ipilimumab + nivolumab (IPI+NIVO) are FDA-approved immunotherapies for advanced melanoma (AM). These two treatment regimens have different toxicity profiles which may impact health care resource utilization (HCRU). Our aim was to compare real-world risk of hospitalization and emergency department (ED) visits within 12 months of starting the two treatment regimens. Methods: A retrospective cohort study was conducted in patients ≥18 years old with AM initiating PEMBRO or IPI+NIVO between Jan 1, 2016 – Dec 30, 2017. Patients were identified from 12 US academic medical centers and affiliated satellite clinics. Data were abstracted through chart review. All-cause hospitalizations or ED visits and the rates per patient per month (PPPM) through 12 months of follow-up were calculated. Utilization was compared between PEMRBO and IPI+NIVO using multivariate logistic regression analysis. Results: 400 patients were included, 200 each PEMBRO and IPI+NIVO with mean (SD) follow-up time of 10 (3) and 10 (4) months, respectively. The PEMBRO cohort had poorer Eastern Cooperative Group (ECOG) performance status at treatment start, 71% ECOG 0 or 1 vs 88% (p < .001); more diabetes, 21% vs 13% (p = .045); a trend towards more heart disease, 18% vs 12% (p = .067); were more likely to be PD-L1 expression positive, 77% vs 63% (p = .011); and less likely to harbor a BRAF mutation, 35% vs 50% (p = .003). The proportion with at least one hospitalization through 12 months was 17% PEMBRO vs 24% IPI+NIVO. Less than 2% of patients had more than one admission and none had more than two, regardless of cohort. Unadjusted mean (SD) PPPM hospitalizations were .016 (.037) for PEMBRO and .020 (.038) for IPI+NIVO. The adjusted odds ratio for any hospitalization with PEMBRO was 0.55 (95% CI .31, .97; p = .039) vs. IPI+NIVO. ED visits occurred in 18% vs 21% in PEMBRO and IPI+NIVO respectively, with no difference in covariate-adjusted analysis (p = .147). Conclusions: Patients receiving PEMBRO had a significantly lower probability of hospitalization and similar probability of ER visits compared with IPI+NIVO in the real world through 12 months.

DREAMM-9: Phase III study of belantamab mafodotin plus VRd versus VRd alone in transplant-ineligible newly diagnosed multiple myeloma (TI NDMM).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. TPS8556-TPS8556 ◽  
Author(s):  
Saad Zafar Usmani ◽  
Evangelos Terpos ◽  
Wojt Janowski ◽  
Hang Quach ◽  
Sarah West ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Residual Disease ◽  
Single Agent ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Complete Response ◽  
Phase Iii ◽  
Clinical Activity ◽  
Efficacy And Safety ◽  
Open Label

TPS8556 Background: Bortezomib, lenalidomide, and dexamethasone (VRd) is the standard of care for transplant-eligible and TI NDMM, but relapse is usually inevitable. The median progression-free survival (PFS) is ~3 years for patients with TI NDMM, and with each relapse, the duration of response (DoR) diminishes, highlighting the need for novel, effective, targeted agents. Single-agent belantamab mafodotin is a first-in-class B-cell maturation antigen–binding, humanized, afucosylated, monoclonal immunoconjugate, showing deep and durable responses in heavily pretreated patients with relapsed/refractory multiple myeloma ( Lancet Oncol2020). Preclinical work suggests belantamab mafodotin plus bortezomib or lenalidomide enhances anti-myeloma activity. Therefore, studying clinical activity of belantamab mafodotin in combination with these agents is warranted. Methods: DREAMM-9 (NCT04091126) is a two-part, open-label study to determine efficacy and safety of single-agent belantamab mafodotin with VRd vs. VRd alone in patients with TI NDMM. Patients aged ≥18 years with ECOG status 0–2 and adequate organ system functions will be eligible. Part 1 (dose selection) will evaluate safety/tolerability of belantamab mafodotin with VRd administered by single (Day 1) or split dosing (Days 1 and 8) in ≤5 cohorts (n = 12/cohort): 1.9 mg/kg, 2.5 mg/kg split and single, and 3.4 mg/kg split and single. Six more patients may be added to cohort(s) most likely to be selected as recommended Phase III dose (RP3D). Dose-limiting toxicities and adverse events (AEs) will be assessed, and belantamab mafodotin RP3D determined through modified toxicity probability interval criteria. Part 2 (randomized Phase III) will determine efficacy and safety of belantamab mafodotin at RP3D with VRd vs. VRd alone (n = 750) in two arms randomized 1:1. Dual primary endpoints will be rate of minimal residual disease (MRD) negativity and PFS. Secondary endpoints will be response rates (overall response, complete response, very good partial response or better, sustained MRD negativity), DoR, time to progression, and overall survival. Safety assessment will include AEs, serious AEs and ocular findings. In both parts, belantamab mafodotin will be given with VRd for eight induction cycles and then with Rd for maintenance until disease progression or unacceptable toxicity. Funding: GlaxoSmithKline (209664). Drug linker technology licensed from Seattle Genetics; monoclonal antibody produced using POTELLIGENT Technology licensed from BioWa. Clinical trial information: NCT04091126 .

scholarly journals Prospective study of Burkitt lymphoma treatment in adolescents and adults in Malawi

2019 ◽  
Vol 3 (4) ◽  
pp. 612-620 ◽  
Author(s):  
Matthew S. Painschab ◽  
Kate D. Westmoreland ◽  
Edwards Kasonkanji ◽  
Takondwa Zuze ◽  
Bongani Kaimila ◽  
...  
Keyword(s):  
Burkitt Lymphoma ◽  
Group Performance ◽  
Performance Status ◽  
Intensive Therapy ◽  
Eastern Cooperative Oncology Group ◽  
Standard Of Care ◽  
Complete Response ◽  
Sub Saharan Africa ◽  
High Dose ◽  
Hiv Viral Load

Abstract Burkitt lymphoma (BL) is common in sub-Saharan Africa (SSA). In high-income countries, BL is highly curable with chemotherapy. However, there are few prospective studies from SSA describing nonpediatric BL and no regional standard of care. Thirty-five participants age 15 years or older with newly diagnosed BL were enrolled in Malawi from 2013 to 2018. Chemotherapy was administered according to institutional guidelines, with concurrent antiretroviral therapy if HIV infected. Median age was 21 years (range, 15-61) and 15 participants (43%) were HIV infected. Twenty-seven participants (77%) had stage III to IV disease, and 19 (54%) had Eastern Cooperative Oncology Group performance status &gt;1. Among HIV-infected participants, median CD4 count was 130 (range, 29-605) and 10 (67%) had suppressed HIV viral load. Four participants (11%) died before receiving chemotherapy. First-line chemotherapy consisted of: cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) (n = 22 [71%]); infusional etoposide, prednisolone, vincristine, cyclophosphamide, and doxorubicin (n = 4 [13%]); high-dose methotrexate-based chemotherapy (n = 4 [13%]); and rituximab plus CHOP (n = 1 [3%]). Among 28 evaluable participants, 14 (50%) achieved a complete response. Median overall survival (OS) was 7 months; 1-year OS was 40% (95% confidence interval [CI], 24%-56%). Sixteen (73%) of 22 deaths were a result of disease progression. Compared with CHOP, more intensive chemotherapy was associated with decreased mortality (hazard ratio, 0.24; 95% CI, 0.05-1.02; P = .05). This is among the best characterized prospective cohorts of nonpediatric BL in SSA. Most deaths resulted from progressive BL. Patients who received more intensive therapy seemed to have better outcomes. Defining optimal approaches is an urgent priority in SSA.

Paclitaxel (P) and cisplatin (C) concurrent with radiotherapy (RT) for larynx preservation (LP) in advanced resectable laryngeal (L) and hypopharyngeal (HP) squamous cell carcinoma (SCC): Final results of a prospective phase II trial.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e16046-e16046
Author(s):  
Ulisses Ribaldo Nicolau ◽  
Thiago Bueno Oliveira ◽  
Andre Lopes Carvalho ◽  
Rosane O Santana ◽  
Adriana D Valadares ◽  
...  
Keyword(s):  
Phase Ii ◽  
Salvage Surgery ◽  
Comparative Trial ◽  
Standard Of Care ◽  
Residual Tumor ◽  
Complete Response ◽  
High Dose ◽  
Standard Regimen ◽  
Term Survival ◽  
Larynx Preservation

e16046 Background: Since the results of the RTOG 9111 trial, cisplatin based chemoradiation (CRT) has been the standard of care for LP in advanced laryngeal SCC. Recently, the role of taxanes in managing head and neck SCC has been studied. In 2002 we reported the interim results of a phase II clinical study designed to test the efficacy of P and C concurrent with RT for organ preservation in advanced L and HP SCC. Here we report the long term survival and LP rates. Methods: Eligible patients had untreated advanced L and HP SCC, stage T3N0 or higher and suitable for radical total laryngectomy. Treatment consisted of weekly P (30 mg/m2) and C (20 mg/m2) concurrent to RT up to 7040 cGy in 180 cGy/day fractions. Response evaluation was performed at 5040 cGy and at 4 weeks after completing RT. Salvage surgery was planned for patients not responding at 5040 cGy, residual tumor at the end of RT or at the time of local recurrence. Neck dissection was planned for clinically positive neck (cN1-3). Results: Between 06/1999 and 10/2001, 48 patients were enrolled in a single institution (35 L; 13 HP), 40 male and 8 female with a 58-year median age (39-74). The majority had T3 (64%) N1-3 (52%) disease and 38% needed tracheostomy prior to treatment. Grade (G) 3 and 4 mucositis was noted in 27% of patients, G 3-4 odynophagia in 50%, G 3-4 radiodermatitis in 35% and G 3-4 leucopenia in 13%, with no treatment related death. Two patients needed salvage surgery, one after 5040 cGy and one after 7040 cGy. The complete response rate to treatment was 95%. At a median follow up of 66 months the LP rate at 2 and 5 years were 88% and 54%, respectively. Recurrence free survival (RFS) was 51% at 2 and 47% at 5 years and overall survival (OS) was 81% and 52% at 2 and 5 years, respectively. Conclusions: The finding of similar LP rate and survival compared to the recent reports of high dose cisplatin CRT and neoadjuvant 3 drug CT followed by CRT in an advanced disease population suggests a role for platinum plus taxane as a radiosensitizer regimen in this scenario with acceptable toxicity, but further evaluation in a direct comparative trial with the standard regimen is needed.

Modified cisplatin, etoposide, and ifosfamide (PEI) salvage therapy for male germ-cell tumors (GCT): Long-term efficacy and safety outcomes.

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 328-328
Author(s):  
Andrea Necchi ◽  
Luigi Mariani ◽  
Nicola Nicolai ◽  
Daniele Raggi ◽  
Elena Farè ◽  
...  
Keyword(s):  
Multivariable Analysis ◽  
Germ Cell Tumors ◽  
Standard Of Care ◽  
Complete Response ◽  
High Dose ◽  
Conventional Dose ◽  
Unselected Patient ◽  
Major Response ◽  
Grade 3

328 Background: Second-line chemotherapy (CT) of advanced GCT is vividly debated and no standard of care has been established. Since 1985 we introduced the modified PEI combination with the aim to reduce toxicity while maintaining efficacy over the original regimen. Methods: We retrieved data of pts who received ifosfamide at 2.5 gr/m2 (with mesna) on days 1-2, etoposide and cisplatin at 100 mg/m2 and 33 mg/m2, respectively, on days 3-5 every 21 days for a maximum of 4 cycles, followed by surgery of residuals. Multivariable analysis (MVA) was undertaken for pre-specified variables and IGCCCG-2 score was analysed as a continuous covariate. ITT analysis was applied. Results: From 02/85 to 01/12, 189 pts failing cisplatin, bleomycin, and vinblastine (PVB, N=25) or etoposide (PEB, N=164) were treated. 87% had a gonadal primary, 50.3% were MSKCC poor risk, 74.7% were IGCCCG-2 intermediate-to-very high risk, 21.8% had liver, bone or brain (LBB) mets, 16.7% were late relapses. 35 pts (18.5%) had a complete response (CR), 68 (35.9%) a marker normalization (PRm-) (major response-rate: 54.4%). 41/68 PRm- were rendered disease-free (total NED-rate: 40.2%). After a median follow-up of 122.1 mos (IQR 71.4-232), median (95%CI) PFS was 7.2 mos (6.2-9.5) and median OS was 21.7 mos (16.7-69.5). 2yr PFS was 34.3% (28.1-41.9) and 5yr OS was 42.1% (35.3-50.2). Mediastinal primary (HR 3.06, 95%CI, 1.68-5.58), LBB mets (HR 2.02, 95%CI, 1.30-3.16), and AFP>1000 ng/mL (HR 2.78, 95%CI, 1.51-5.14) were negative prognostic factors for OS at MVA while no effect was seen according to IGCCCG-2 category. 70.3% of grade 3-4 neutropenia (25% febrile neutropenia), 48.1% thrombocytopenia, 21.1% anemia, 3% neurotoxicity, and no severe renal toxicity were recored. 81 pts (78% before 2000) had a dose reduction of ≥1 drug for ≥1 cycle. No discontinuations for toxicity occurred. Conclusions: Dose-modified Italian PEI showed activity comparable with the best ones achievable by conventional-dose CT (CDCT) in an unselected patient population, and a favorable toxicity profile. Results are among the most robust available for a CDCT, and should be considered as an appropriate benchmark to be compared with high-dose CT.

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