Post Transplant Brentuximab Maintenance Appears More Effective Than Post Transplant Salvage Brentuximab for Relapsed/Refractory Hogkin's Lymphoma

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5357-5357 ◽  
Author(s):  
Amanda Chidiac ◽  
Radwan Massoud ◽  
Mohamad Haidar ◽  
Elie Fares ◽  
Ali Bazarbachi ◽  
...  
Keyword(s):  
High Risk ◽  
Maintenance Therapy ◽  
Hodgkin Lymphoma ◽  
Salvage Therapy ◽  
Medical Center ◽  
American University ◽  
Post Transplant ◽  
American University Of Beirut ◽  
Risk Patients

Abstract POST TRANSPLANT BRENTUXIMAB MAINTENANCE APPEARS MORE EFFECTIVE THAN POST TRANSPLANT SALVAGE BRENTUXIMAB FOR RELAPSED /REFRACTORY HODGKIN LYMPHOMA Amanda Chidiac1, Radwan Massoud 1, Mohamad Haidar1, Elie Fares1, Ali Bazarbachi1 and Jean El Cheikh1 1Bone Marrow Transplantation Program, American University of Beirut Medical Center, Beirut, Lebanon Keywords: Hodgkin Lymphoma, Relapsed/Refractory, Brentuximab. Context: Brentuximab Vedotin (BV) is a chimeric anti CD30 IgG1 antibody, conjugated to synthetic antitubulin momomethyl auristatin. BV is approved for the treatment of classical HL in relapse either after autologous stem cell transplantation (ASCT) or after two lines of combination chemotherapy in transplant ineligible patients. The AETHERA trial revealed increased PFS when BV is used as maintenance therapy after ASCT. Objective: Compare the effectiveness of BV as maintenance or salvage therapy after ASCT for relapsed/refractory (R/R) HL. Design: A retrospective analysis conducted on patients with R/R HL treated with BV after ASCT either as maintenance or salvage therapy. Analysis after a median follow up of 12 months is reported. Setting: The study was conducted in a single institution; American University of Beirut Medical Center (AUBMC) after IRB approval. Patients: The study included 15 adult patients with R/R HL treated with BV with the following indications: á Maintenance therapy after ASCT in high risk patients á Salvage therapy for relapse after ASCT or allo-SCT Intervention: BV at 1.8mg/kg IV every 4 weeks for the above indications. Main outcome measures: response rate (RR), overall survival (OS) and progression free survival (PFS). Results: Nine high-risk patients (60%) received 4 cycles of BV as maintenance therapy post ASCT. Six additional patients (40%) in relapse after ASCT (n=5) or after allo-SCT (n=1) received BV as salvage therapy for an average of 4 cycles (range 3-21). Patients characteristics are listed on Table 1. RR was 33% in 6 patients who received BV as salvage post SCT. Two patients proceeded with allo-SCT in the salvage group. After a median follow up of 9 months, only 2 patients (22%) in the maintenance group progressed and all patients are still alive. Conversely, in the salvage group, 4 patients (67%) progressed and 1 patient developed secondary AML and died. Conclusion: BV therapy showed an efficacy only as maintenance treatment after auto-SCT but was less successful when used as post-transplant salvage in R/R HL. Four cycles of maintenance may suffice. Prospective trials with larger samples are warranted to support these findings. Disclosures No relevant conflicts of interest to declare.

Impact of proteasome inhibitor vs. IMiD maintenance therapy on outcomes of patients with high-risk multiple myeloma (HRMM).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e20557-e20557
Author(s):  
Eric Leon Tam ◽  
David Joseph Iberri ◽  
Michaela Liedtke ◽  
Lori S. Muffly ◽  
Parveen Shiraz ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
High Risk ◽  
Maintenance Therapy ◽  
Proteasome Inhibitor ◽  
Post Transplant ◽  
Risk Patients ◽  
To Receive ◽  
Standard Risk

e20557 Background: The ideal choice of maintenance therapy in patients with HRMM high-risk multiple myeloma remains unknown. We analyzed the outcomes of patients with HRMM undergoing transplant receiving different maintenance approaches. Methods: Patients with MM undergoing their first ASCT from 2012-19 within 1 year of diagnosis were identified from the prospectively maintained database of patients undergoing ASCT. HRMM was defined as having t(4;14), t(14;16), t(14;20), del17p13, or gain 1q detected on fluorescent in situ hybridization (FISH). Results: Of the 412 patients undergoing ASCT within 1 year of diagnosis, 333 had FISH data available and of these, 37% (124/333) patients had high-risk cytogenetics. Distribution of HR cytogenetics was as follows: deletion 17p: 37% (n = 46), t(4;14): 27% (n = 34), t(14;16) or t(14;20): 12% (n = 26), gain1q: 31% (n = 41). 9% (n = 12) had more than one HR abnormality. In patients with HRMM, median age at transplant was 59 years (range: 39 to 73), and 61% (n = 103) were males. 64% (n = 107) of high-risk patients received post-transplant maintenance therapy. Maintenance therapy in this group included a proteasome inhibitor (PI) in 34% (n = 29), immunomodulatory drug (IMiD) in 59% (n = 51), or both in 7% (n = 6). There was no difference in baseline characteristics of HRMM patients receiving PI vs. IMiD maintenance, except that patients with del17p were more likely to receive PI maintenance therapy (55% vs 28%, p = 0.01). (Table) After a median follow-up of 3.1 years from diagnosis, patients with HRMM had inferior PFS compared to patients with standard risk disease, with median PFS of 3 vs. 4.8 years, p < 0.001. Amongst the 86 HRMM patients receiving maintenance therapy, median PFS in patients receiving PI vs. IMiD vs. both PI + IMiD maintenance was 3 vs. 3.2 vs. 2.2 years, respectively, log-rank p = 0.7. In the sub-group of patients with 17p deletion, median PFS in the three groups was 3 vs. 2.9 vs. 2.2 years, respectively, log-rank p = 0.7. Conclusions: Patients with HRMM have inferior PFS compared to patients with standard risk disease. We observed similar outcomes in HRMM patients post-transplant regardless of the choice of maintenance therapy. [Table: see text]

scholarly journals SUMMIT (Serially Unified Multicenter Multiple Sclerosis Investigation): creating a repository of deeply phenotyped contemporary multiple sclerosis cohorts

2017 ◽  
Vol 24 (11) ◽  
pp. 1485-1498 ◽  
Author(s):  
Riley Bove ◽  
Tanuja Chitnis ◽  
Bruce AC Cree ◽  
Mar Tintoré ◽  
Yvonne Naegelin ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
San Francisco ◽  
Medical Center ◽  
Clinically Isolated Syndrome ◽  
American University ◽  
American University Of Beirut ◽  
Longitudinal Investigation ◽  
American Academic

Background: There is a pressing need for robust longitudinal cohort studies in the modern treatment era of multiple sclerosis. Objective: Build a multiple sclerosis (MS) cohort repository to capture the variability of disability accumulation, as well as provide the depth of characterization (clinical, radiologic, genetic, biospecimens) required to adequately model and ultimately predict a patient’s course. Methods: Serially Unified Multicenter Multiple Sclerosis Investigation (SUMMIT) is an international multi-center, prospectively enrolled cohort with over a decade of comprehensive follow-up on more than 1000 patients from two large North American academic MS Centers (Brigham and Women’s Hospital (Comprehensive Longitudinal Investigation of Multiple Sclerosis at the Brigham and Women’s Hospital (CLIMB; BWH)) and University of California, San Francisco (Expression/genomics, Proteomics, Imaging, and Clinical (EPIC))). It is bringing online more than 2500 patients from additional international MS Centers (Basel (Universitätsspital Basel (UHB)), VU University Medical Center MS Center Amsterdam (MSCA), Multiple Sclerosis Center of Catalonia-Vall d’Hebron Hospital (Barcelona clinically isolated syndrome (CIS) cohort), and American University of Beirut Medical Center (AUBMC-Multiple Sclerosis Interdisciplinary Research (AMIR)). Results and conclusion: We provide evidence for harmonization of two of the initial cohorts in terms of the characterization of demographics, disease, and treatment-related variables; demonstrate several proof-of-principle analyses examining genetic and radiologic predictors of disease progression; and discuss the steps involved in expanding SUMMIT into a repository accessible to the broader scientific community.

Functional Imaging in Children and Adolescents with Relapsed or Refractory Hodgkin Lymphoma and Outcome after Autologous Transplantation

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2264-2264
Author(s):  
Nmazuo Ozuah ◽  
Hisham Dahmoush ◽  
Frederick Grant ◽  
Leslie Lehmann ◽  
Amy Billett ◽  
...  
Keyword(s):  
Stem Cell ◽  
Complete Remission ◽  
Children And Adolescents ◽  
Hodgkin Lymphoma ◽  
Functional Imaging ◽  
Salvage Therapy ◽  
Salvage Chemotherapy ◽  
Refractory Disease ◽  
Post Transplant

Abstract Introduction Children and adolescents with Hodgkin lymphoma (HL) have excellent long-term outcomes after combined modality treatment, however ~15-20% will either relapse or have primary refractory disease. (Shankar A, BJH 2014) Salvage chemotherapy followed by autologous stem cell transplantation (ASCT) is the standard of care for many pediatric patients with relapsed HL. In adults, achieving a complete remission by functional imaging (FI), particularly positron emission tomography (PET), after salvage chemotherapy is a strong predictor of outcome after ASCT. The majority of published data in pediatric cohorts has employed computed tomography (CT) measurements to assess pre-transplant disease status. We report pre-ASCT FI and clinical outcomes of 49 consecutive children/adolescents, who underwent ASCT for relapsed/refractory HL at our institution. Patients and Methods Following IRB approval, the records of 49 patients with relapsed/refractory HL who received ASCT from January 1, 2001 to December 31, 2014 were reviewed. All had PET (43) or gallium (6) at time of relapse and subsequent time points in disease evaluation pre-ASCT. Available PET scans were reviewed by 2 nuclear medicine physicians, blinded to the clinical data, and assigned Deauville scores. 12 patients who did not have available PET images had outside reports documenting negative PET upon completion of initial salvage therapy. Negative FI was defined as interval resolution of previous gallium avid disease, documented negative PET, or Deauville score ≤ 3. Relapse therapy regimens varied. Patients received standard conditioning regimen with carmustine, etoposide, cytarabine and melphalan(BEAM) followed by stem cell infusion. Post-transplant radiation therapy (RT) was given if no prior RT to the site(s) of relapse. Overall survival (OS) was measured from the date of transplant to death from any cause, progression free survival (PFS) defined as a relapse of HL, with non-HL-related deaths censored. (Lieskovsky JCO, 2004) OS and PFS distributions were examined using Kaplan-Meier curves and the differences between groups were analyzed using the log-rank test and a significant P value < 0·05. Results Median age at time of transplant was 16.4 years; 55% of patients were males. Eighteen (37%) had refractory disease, 22 (45%) relapsed early (3-12 months from completion of primary therapy) and 9 (18%) relapsed late (>12 months).Thirty-one (63%) relapsed within initial RT field. First-line and salvage therapy regimens are detailed in Table 1. Fourteen (27%) received ≥2 salvage therapies; 3 had a 3rd line agent. Nine of the 14 (64%) later achieved negative FI. Three patients with positive PET after initial salvage therapy did not receive a 2nd line regimen. Pre-ASCT,41 patients (84%) had negative FI vs 8 (16%) with positive FI. Eighteen patients (37%) received post-transplant RT; including 5 (64%) in the positive FI group and 13 (32%) in the negative FI group. Median duration of follow up post-transplant was 45.6 months (1-180 months). Forty-five patients were alive and disease-free at last follow up. Post-transplant events included 2 early deaths from transplant-related complications, 1 motor vehicle accident and 1 relapse 6 months post-transplant (pre-transplant Deauville score of 5, death at 12 months). No patient developed a second malignancy. 3-year OS for entire cohort was 92% (95% CI 78-97) with PFS of 98% (95% CI 86-99). 3-year PFS was 100% vs 86% (95% CI 33-98) in negative and positive FI groups respectively (p=0.02). 3-year OS for negative and positive FI patients was 95% (95% CI 82-99) vs 75% (95% CI 31-93) respectively (p=0.06). Complete remission by FI after initial salvage therapy was associated with a trend in OS (97% vs 82% in those with persistent disease) (p=0.08) but not PFS. Extra-nodal disease at relapse, refractory disease and radiation-field relapse had no significant impact on either OS or PFS in a univariate analysis. Cox proportional hazard ratios could not be performed on multivariate analysis given rarity of events. Conclusion Our analysis revealed outstanding outcomes for children/adolescents with relapsed/refractory HL. Negative pre-ASCT PET or gallium was associated with excellent PFS and OS but there were too few relapses to identify the predictive value of pre-transplant FI. Patients who do not achieve complete metabolic response to second line salvage therapy may be candidates for novel approaches. Disclosures No relevant conflicts of interest to declare.

Risk-adapted therapy utilizing upfront brentuximab vedotin (Bv) and rituximab (R) with reduced toxicity chemotherapy in children, adolescents, and young adults with Hodgkin lymphoma.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 10532-10532
Author(s):  
Jessica Hochberg ◽  
Liana Klejmont ◽  
Lauren Harrison ◽  
Allyson Flower ◽  
Quihu Shi ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
High Risk ◽  
Hodgkin Lymphoma ◽  
Combination Chemotherapy ◽  
Early Response ◽  
Brentuximab Vedotin ◽  
Response To Therapy ◽  
Newly Diagnosed ◽  
Risk Patients

10532 Background: Cure rates for CAYA patients with Hodgkin Lymphoma remain high, however are limited by significant toxicity of chemoradiotherapy. Brentuximab Vedotin and Rituximab have shown efficacy in relapsed HL. We hypothesize that the addition of both to combination chemotherapy will be safe in newly diagnosed HL preserving current EFS with elimination of more toxic chemoradiotherapy. Objective: To evaluate the safety and overall response and EFS of Brentuximab and Rituximab in combination with risk adapted chemotherapy in CAYA with newly diagnosed HL. Methods: Age 1-30 yrs with newly diagnosed classical HL given 3 to 6 cycles of chemoimmunotherapy: Brentuximab vedotin with Doxorubicin, Vincristine, Prednisone and Darcarbazine (Bv-AVPD) for Low risk patients or Doxorubicin, Vinblastine, Darcarbazine and Rituximab (Bv-AVD-R) for Intermediate/High risk. Early response measured by PET/CT scan following 2 cycles. Slow responders received an additional 2 cycles of Bv-AVD-R for Intermediate Risk or Ifosfamide/Vinorelbine for High Risk patients. Radiation therapy was given ONLY to those patients not in CR. Results: Total = 19 patients. Median age = 15yr (range 4-23yr). Risk = 2 low, 13 intermediate, 4 high. Toxcity = 1 episode of GrIII mucositis, 1 episode of GrIII infusion reaction to Brentuximab. 17 patients have completed therapy. All 17 patients achieved a complete response to therapy for a CR = 100%. Eleven (58%) have achieved a rapid early response. No patient has required radiation therapy. For 17 patients who have completed therapy, the EFS and OS is 100% with a median follow up time of 915 days (30 months). Conclusions: The addition of Brentuximab vedotin and Rituximab to combination chemotherapy for newly diagnosed Hodgkin Lymphoma appears to be safe. Our early results show significant promise with a CR rate of 100% and 58% rapid early response. We have successfully deleted toxic alkylator, topoisomerase inhibitor, bleomycin and radiation from this treatment regimen. The EFS/OS to date is 100% with a median follow up time of 2.5 years. Further follow up and a larger cohort is needed to determine long term outcomes of this approach. Clinical trial information: NCT02398240.

scholarly journals Reducing the Burden of Chemoradiotherapy with the Combination of Brentuximab Vedotin and Rituximab with Reduced Toxicity Chemotherapy in Children, Adolescents and Young Adults with Newly Diagnosed Hodgkin Lymphoma

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 127-127
Author(s):  
Jessica C. Hochberg ◽  
Jaclyn Basso ◽  
Liana Klejmont ◽  
Lauren Harrison ◽  
Allyson M. Flower ◽  
...  
Keyword(s):  
Young Adults ◽  
High Risk ◽  
Hodgkin Lymphoma ◽  
Early Response ◽  
Brentuximab Vedotin ◽  
Adolescents And Young Adults ◽  
Newly Diagnosed ◽  
Risk Patients ◽  
Stage Ia

Background: Cure rates for newly diagnosed Hodgkin Lymphoma remain high through the combined use of chemoradiotherapy. (Hochberg/Cairo Cancer Journal 2018) However, this has resulted in significant adverse physical and psychosocial function that significantly impacts the quality of life among survivors, including cardiotoxicity, neurocognitive deficits, poor quality of life, and secondary malignancies. Pediatric cancer survivor studies have shown significant increases adverse health events following therapy throughout adulthood. Major risk factors for late effects include significant exposure to radiation, anthracyclines, cyclophosphamide, etoposide and bleomycin. (Bhakta et al Lancet 2017, Oeffinger et al NEJM 2006, Gibson et al Lancet Oncol 2018) Immunotherapy targeting the Reed Sternberg cell and tumor microenvironment, including regulatory B-cells, has potential to reduce the burden of traditional treatment. Brentuximab Vedotin, an anti-CD30 antibody-drug conjugate, and Rituximab, a chimeric anti-CD20 monoclonal antibody, have both shown efficacy in relapsed Hodgkin Lymphoma and Brentuximab has gained FDA approval in up front adult HL in combination with standard chemotherapy. (Younes et al JCO 2012, Younes et al Blood 2012, Connors et al NEJM 2018) We hypothesized that the addition of Brentuximab vedotin (Bv) and Rituximab (R) combined with risk adapted chemotherapy will be well tolerated and effective in children, adolescents and young adults with all stages of newly diagnosed Hodgkin lymphoma and will allow for the elimination of more toxic chemotherapies as well as need for radiation. Objectives: To evaluate the safety, tolerability and overall response rate of Brentuximab vedotin and Rituximab in combination with risk adapted chemotherapy in children, adolescents and young adults with newly diagnosed Hodgkin Lymphoma. Methods: Eligible patients 1-30 yrs with all stages of newly diagnosed classical Hodgkin Lymphoma. Patients were risk assigned as either Low (Stage IA, IIA, no bulk), Intermediate (Stage IA bulk/E, IB, IIA bulk, IIB or IIIA) and High Risk (Stage IB bulk/E, II bulk, IIIA bulk, IIIB, IV). Low risk patients were given 3 cycles of Brentuximab vedotin (1.2mg/kg) with Doxorubicin (25mg/m2), Vincristine (1.5mg/m2), Prednisone and Dacarbazine (375mg/m2) on Days 1 and 15. Intermediate and High Risk patients received 4 or 6 cycles of Brentuximab vedotin, Doxorubicin, Vinblastine, Dacarbazine and Rituximab (375mg/m2) on Days 1,2 and 15, 16. (Figure 1) Early response was measured by PET/CT scan. Slow responders, defined by lack of a complete metabolic response or &lt;80% size reduction, received an additional 2 cycles of Bv-AVD-R for Intermediate Risk or Ifosfamide/Vinorelbine for High Risk. Involved Field RT was restricted to only patients with bulk disease with SER and those not in a CR at the end of therapy. Humoral and cellular immunity was measured upon completion of therapy. Results: Total enrolled = 33 patients. Median age = 15yr (range 4-23yr). Total 12 males, 21 females. Risk Assignment = 4 low, 17 intermediate, 12 high. Toxicity = 1 episode of Gr III mucositis, 1 episode of Gr III infusion reaction to Brentuximab vedotin, 2 episode Gr III peripheral neuropathy. All 33 patients achieved a complete response for a CR = 100%. Eighteen patients (58%) achieved a rapid early response. Four patients (only 12%) have required radiation therapy to date due to the presentation of bulky disease with a slow early response. Each of these patients was in CR prior to the start of radiation therapy. At a median follow-up of 18 months, the mean±SEM IgG level, CD19 and CD3 levels were 1097±63, 325±105, and 1273±290, respectively, all within normal range. Furthermore, none of the patients developed agammaglobulinemia or required hospitalization for systemic infection during or following treatment. The EFS and OS is 100% with a mean follow up time of 1320 days (= 44 months, range 3-80). (Figure 2) Conclusions: The addition of Brentuximab vedotin and Rituximab to combination risk adapted chemotherapy (without cyclophosphamide, etoposide or bleomycin) for newly diagnosed Hodgkin Lymphoma appears to be safe in children, adolescents and young adults. Our results show significant promise with a CR rate of 100%, 58% rapid early response and significant reduction in the use of toxic chemotherapy and radiation. The EFS/OS to date is 100% with a median follow up time of greater than 3.5 years. Disclosures Cairo: Osuka: Research Funding; Miltenyi: Other: MTA; Jazz Pharmaceuticals: Other: Advisory Board, Research Funding, Speakers Bureau.

Total Therapy 2 (No Thalidomide Arm, TT2-) Is Superior to Total Therapy 1 (TT1) for Newly Diagnosed Multiple Myeloma (MM): Doubling 4-Yr Survival among Patients with Cytogenetic Abnormalities (CA) Due to Consolidation Chemotherapy (CCT) and DEX Maintenance.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1152-1152
Author(s):  
Bart Barlogie ◽  
Guido Tricot ◽  
Erik Rasmussen ◽  
Elias Anaissie ◽  
Frits van Rhee ◽  
...  
Keyword(s):  
High Risk ◽  
Phase Iii ◽  
Completion Rates ◽  
Phase Iii Trial ◽  
Post Transplant ◽  
Historical Comparison ◽  
Risk Patients ◽  
Total Therapy ◽  
Intent To Treat

Abstract Background: TT2 introduced T into the frontline therapy for MM in a randomized phase III trial design (ASCO 2005). In comparison to TT1, TT2 applied: (1) more intensive chemotherapy for induction prior to and introduced CCT after melphalan 200mg/sqm-based tandem autotransplants, designed to improve survival in high-risk patients with CA; (2) DEX pulsing was added during the 1st year of interferon (IFN) maintenance therapy. We now report on the outcome of patients treated on the “no thalidomide” arm of TT2 (TT2-) in comparison to TT1, in order to evaluate the effect of dose-intensification during induction and post-transplant therapy. Patients and Methods: 231 patients were enrolled in TT1 (median follow-up, 11yr) and 345 in TT2- (median follow-up, 3.5yr). Completion rates of 1st/2nd transplants were 195/165 (84%/71%) with TT1 and 292/235 (85%/68%) with TT2-. In TT2-, 64% started CCT and 36% received DEX consolidation (when platelets failed to recover or no benefit was documented from induction DCEP). TT2- and TT1 were compared in terms of pre-transplant-1 and final CR rates (intent-to treat), EFS/OS from treatment start, 1st transplant and from last (2nd or 1st) transplant. EFS and OS were examined in the context of baseline prognostic variables including CA. Results: Compared to TT1, TT2- induced similar pre-Tx1 CR rates (11% vs 12%, p=0.8) and final CR rates (41.3% vs 40.7%, p=0.9). The median onset of CR was 8.9mo for TT2 vs 8.4mo for TT1 (p=0.4). 5-year EFS/OS were 45%/63% with TT2- vs 28%/57% with TT1 (p&lt;0.001/p=0.06). 4-yr post-transplant-1 EFS/OS were 48%/65% with TT2- vs 28%/56% with TT1 (p&lt;0.001/p=0.02); 4-yr post-transplant-2 EFS/OS were 46%/64% with TT2- and 31%/50% with TT1 (both p=0.01). Pre-study CA, high LDH (&gt;=190U/L), and low Hb (&lt;10g/dL) were independently, significantly associated with poorer post-transplant-2 EFS and OS (p&lt;0.05); independent of these factors, TT2- improved post-transplant-2 EFS and OS compared to TT1 (p&lt;0.001/p=0.033). In the presence of CA, TT2- with CCT vs TT2- with DEX improved 4-yr OS (measured from a 6-mo landmark post-transplant-2) from 37% (similar to 39% with TT1 [no DEX or CCT]) to 78%, which is comparable to the 65% for TT1 without CA. Conclusion: In this historical comparison of TT1 with TT2-, the more intensive induction chemotherapy with TT2- did not improve CR. However, post-transplant CCT benefited the 1/3 of patients with CA, doubling 4-yr post-transplant OS in comparison with TT1 in this high-risk subgroup. A phase 3 randomized trial addressing the CCT concept is warranted. Figure Figure

For Standard and High-Risk Patients with Hodgkin Lymphoma Six Cycles of Tailored BEACOPP, Based On Interim Scintigraphy, Are Effective and Female Fertility Is Preserved.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1552-1552 ◽  
Author(s):  
Eldad Dann ◽  
Rachel Bar-Shalom ◽  
Ada Tamir ◽  
Menachem Ben-Shachar ◽  
Irit Avivi ◽  
...  
Keyword(s):  
High Risk ◽  
Hodgkin Lymphoma ◽  
Young Female ◽  
Prognostic Features ◽  
High Risk Patients ◽  
Female Patients ◽  
Interim Pet ◽  
Pet Ct ◽  
Risk Patients

Abstract Abstract 1552 Poster Board I-575 This prospective study (124 patients) evaluated the outcome of patients with Hodgkin lymphoma (HL) whose therapy was tailored based on results of scans performed after 2 cycles of chemotherapy, thus reducing the dose for early responders and maximizing the dose for those with subptimal early response or progression. The study was initiated in 1999 for patients with HL aged 18-60 years. Eligibility criteria were: unfavorable HL stages I, II and stage III or IV. Disease was defined according to the International Prognostic Score (IPS). Standard risk patients were treated with 2 cycles of standard BEACOPP (SB) and those with IPS of 3 3 got 2 cycles of escalated BEACOPP (EB): Ga67(on 57 patients prior to 2001) or hybrid PET/CT scan (on all 67 since 2001) were performed at diagnosis and after the 1st or 2nd cycle for all 124 patients. If early interim scan remained positive, additional 4 cycles of EB were used; otherwise, SB was given. Data for 108 patients were previously reported (Blood, 2007); albeit with a median follow-up of only 4 years. Herein is an updated 6- year median follow-up for all previously reported patients who had Ga67 or PET/CT as well as 16 additional patients who underwent interim PET/CT. Furthermore, importantly, the fertility of all young female patients is herein reported. For all 124 patients on study, the 7-year event-free survival (EFS) for patients with IPS 0-2 is 89% and for those with IPS of 3 3 87%. Seven year overall survival (OS) is 90%. Sixty seven patients (39 males and 28 females aged 18-55 [median 33]) were treated after 2001 when hybrid FDG-PET/CT became available. Forty one patients had IPS of 0-2 and 26 ≥3. Complete remission (CR) rate was 96%, 5-y FFS and OS were 92% and 97%, respectively at a median follow-up of 56 months (8-90). 5-y EFS and OS were similar for standard and high risk patients. HL progressed in 2/12 patients with interim positive PET/CT versus 3/55 with negative PET (p<0.02) (Table 1). Ninety four percent of patients with negative interim PET/CT had no disease progression during the follow-up, while 17% of patients with interim positive PET/CT progressed. One patient died from breast cancer. Thirty-eight females < 40 years old who had been treated with tailored BEACOPP since 1998 were assessed for fertility status. This is described in Table 2. Twenty six were co-treated with the GnRH agonist triptorelin, concomitantly with chemotherapy. Nineteen conceived during follow-up. Thirteen delivered 17 healthy babies, 6 terminated their pregnancy. Conclusion PET/CT is useful for making an early interim decision about chemotherapy dose on an individual basis, thus reducing unnecessary toxicity and escalating therapy where appropriate based on poor interim prognostic features. The results of 6 cycles of risk-adapted BEACOPP compare favorably with the reported data following 8 cycles of EB. Use of tailored therapy enables reduction of cumulative chemotherapy and preservation of fertility in the majority of young female patients. Disclosures Rowe: Teva Pharmaceuticals: Consultancy; EpiCept Corporation: Consultancy.

scholarly journals Allogeneic Stem Cell Transplantation As Salvage Therapy for First Relapse after Autografting in Multiple Myeloma Patients

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4619-4619
Author(s):  
Evgeny Klyuchnikov ◽  
Christine Wolschke ◽  
Anita Badbaran ◽  
Maximilian Christopeit ◽  
Ute-Marie von Pein ◽  
...  
Keyword(s):  
High Risk ◽  
Maintenance Therapy ◽  
Salvage Therapy ◽  
Research Funding ◽  
Univariate Analysis ◽  
Landmark Analysis ◽  
Post Transplant ◽  
Remission Duration ◽  
First Relapse ◽  
Grade Ii

Abstract Despite the significant improvement in outcomes for myeloma patients (pts) in the more recent years (yrs), the disease remains incurable. Because of high morbidity and mortality the role of allo-SCT in treatment of myeloma remains controversial. Registry data from the European Society of Blood and Marrow Transplantation (EBMT) suggest an increasing use of allo-SCT as salvage therapy after failure to auto-SCT. In present single center study we provide data on the use of allo-SCT focusing on pts with first relapse/progressive disease after autografting. A total of 89 pts (males, 62%) with median age of 53y (24-73) relapsed after an autograft (single, 64%; tandem, 36%) and received an allo-SCT during 2000 - 2015 yrs at University of Hamburg were included. The majority of the pts experienced advanced disease (stage III, 80%) and short remission duration after auto-SCT (≤24 mo, 81%) with median of 15 mo (2-91). A total of 76% of pts received a reinduction therapy prior to allo-SCT, whereas 24% did not. Twelve pts (14%) had high risk cytogenetics (defined as detection of del17p and/or t(4;14) by FISH). Twelve pts experienced extramedullary relapses. At time of transplantation pts were in CR (10%), vgPR (22%), PR (27%), SD (16%) or PD (25%). Allo-SCTs were performed mostly with peripheral stem cell (92%) and from unrelated (matched, 40%; mismatched, 32%) donors. Myeloablative conditioning was used in 70% of pts (busulfan-based, 61%; treosulfan-based, 9%). A total of 28 pts (31%) received a maintenance therapy (lenalidomide, 79%) starting at median 6 mo (4-8) post-transplant. Furthermore, 19 pts (24%) received DLIs (positive immunofixation, n=15; prophylaxis, n=4) within a median of 10 mo (4-27). The cumulative incidence (CI) of acute GvHD (grade II-IV) at d100 was 43% (32-55%). The CI of chronic GvHD at 5y post-transplant was 51% (39-63%; mild, n=19, moderate, n=12, severe, n=5). Of the 19 pts receiving DLIs, 5 (26%) developed GvHD (grade II-IV). Six (40%) of 15 pts responded (CR). The CI of TRM at d100 and at 5y were 8% (4-16%) and 19% (12-28%), respectively. We observed improved TRM in pts who didn't receive radiation before allo-SCT (p=0,03). The CI of relapses at 5y was 61% (49-72%). We observed a trend to lower relapse rate of 29% in pts with longer remission duration (>24 mo, p=0,07). The 5y probability of EFS was 28% (19-39%). The median EFS was 29 mo (22-36). In univariate analysis, we observed decreased survival probability for pts with high risk cytogenetics (p=0,026), remission duration ≤24 mo (p=0,008) and non-responders to salvage therapy (p=0,037). In multivariate analysis the negative impact of remission duration ≤24 mo (HR 6,9; 1,8-25,6; p=0,004) and failure to salvage therapy (HR 3,3; 1,2-9,0; p=0,021) were confirmed. In landmark analysis at d100 we observed improved survival for responding pts (p<0,001), pts in CR (p=0,028), those in "stringent" CR compared to CR (p=0,014) and those with negative MRD (minimal residual disease, FACS, p=0,037). Intriguingly, the median EFS for pts in "stringent" CR was not reached. In landmark analysis at 6 mo we observed improved survival for pts receiving preemptive/prophylactic DLIs (p=0,045). After a median follow up of 48 mo (6-170), the 5y probability of OS was 57% (46-78%). The median OS was 76 mo (42-110). In univariate analysis, we observed decreased survival probability for pts with extramedullary relapse (p=0,039), high risk cytogenetics (p=0,001), remission duration ≤6 mo (p=0,044) and those who received reduced intensity conditioning (p=0,022). In multivariate analysis the negative impacts of extramedullary relapses (HR 7,3; 2,7-20; p<0,001), reduced intensity conditioning (HR 3,5; 1,4-8,5; p=0,006) and short remission duration (HR 2,6; 1,1 - 6,2; p=0,038) were confirmed. In landmark analysis at d100 we observed improved survival for responding pts (p<0,001), pts in CR (p=0,028) and those in "stringent" CR compared to CR (p=0,014). In landmark analysis at 6 mo we observed improved survival for pts receiving DLIs (p<0,001) and maintenance therapy (p=0,002). Allo-SCT being performed as salvage therapy after autograft failure resulted in around 30% 5y EFS. The response on d100 post-transplant, augmented by the MRD detection, seems to be prognostic important and might be used for planning further therapeutic strategies post-transplant. The use of DLIs and maintenance therapy post-transplant represent a possible approach to further improve survival. Disclosures Kröger: Sanofi: Honoraria, Research Funding; Neovii: Honoraria, Research Funding; Riemser: Honoraria, Research Funding; Novartis: Honoraria, Research Funding.

Risk Stratification in Acute Promyelocytic Leukemia Based on Elevated White Cell Count and Reduced Platelet Count Does Not Identify Subsequent Relapses: A Retrospective Review of 60 Patients.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4522-4522
Author(s):  
Richard T. Doocey ◽  
Stephen H. Nantel ◽  
Michael J. Barnett ◽  
Donna L. Forrest ◽  
Donna E. Hogge ◽  
...  
Keyword(s):  
High Risk ◽  
Complete Remission ◽  
Maintenance Therapy ◽  
Risk Group ◽  
White Cell Count ◽  
High Risk Group ◽  
Low Risk ◽  
Intermediate Risk ◽  
Risk Patients

Abstract Acute promyelocytic leukemia (APL) has become one of the more readily treatable subtypes of acute myeloid leukemia on the basis of its particular sensitivity to anthracyclines and the introduction of the differentiating agent all-trans retinoic acid (ATRA). Unfortunately some patients will ultimately relapse after achievement of complete remission. A PETHEMA and GIMEMA (PETH/GIM) cooperative group joint study sought to identify risk factors associated with relapse and developed a predictive model based on white cell count (WCC) and platelet count (Plt) at diagnosis. This model for relapse free survival was capable of segregating patients into low risk (WCC &lt; 10 x 109/L / Plt &gt; 40 x 109/L), intermediate risk (WCC &lt; 10 x 109/L / Plt &lt; 40 x 109/L), and high risk (WCC &gt; 10 x 109/L). A subsequent follow up study demonstrated improved outcomes for intermediate and high risk group patients treated with an anthracycline and ATRA based risk adapted strategy. We reviewed 60 cases of adult de novo APL treated at Vancouver General Hospital from August 1995 to December 2003. Thirty five females (58%) and 25 males (42%) were treated with a standard induction and consolidation protocol consisting of 3 cycles of Daunorubicin (60 mg/m2 OD for 3 days), Cytosine arabinoside (100 mg/m2 BID for 7 days), and ATRA (45 mg/m2/day until complete remission or a maximum of 60 days). In 2000 maintenance therapy was introduced and ATRA and/or varying doses of Methotrexate and 6-Mercaptopurine were then instituted for up to 2 years duration. At the completion of induction chemotherapy complete morphological and cytogenetic remission was achieved in 55/60 patients (92%) with 4 induction failures and only 1 death during induction treatment. Subsequently during and after consolidation and maintenance therapy at a median follow up of 34 months there were a total of 10 episodes of relapse (18%) in these 55 patients. When the 55 patients in complete remission were stratified at diagnosis by the PETH/GIM risk group there were 18 low risk patients (33%), 26 intermediate risk patients (47%), and 11 high risk patients (20%). The number of relapses was 6 in the low risk group (33%), 4 in the intermediate risk group (15%) and no relapses were identified in the high risk group. In our experience the predictive model for relapse free survival developed by the PETH/GIM cooperative group does not identify those at most likelihood for subsequent relapse after achieving an initial complete remission. The greatest number of relapse was seen in the low risk group with no relapses in the high risk group. These variations may be explained in part by the different chemotherapy treatment protocols with variable maintenance therapy. Future investigation will focus on the prognostic role of immunophenotype, additional cytogenetic abnormalities and molecular isoforms in determining outcome in APL.

The Outcome Of Patients With Post Transplant and Immunodeficiency Associated Lymphoproliferative Disorder: The BCCA Experience

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4390-4390
Author(s):  
Amrit Kahlon ◽  
Graham W. Slack ◽  
Yuhua Sun ◽  
Richard Klasa ◽  
Laurie H. Sehn ◽  
...  
Keyword(s):  
High Risk ◽  
Hodgkin Lymphoma ◽  
Combination Chemotherapy ◽  
Research Funding ◽  
Single Agent ◽  
Lymphoproliferative Disorders ◽  
Grey Zone ◽  
Post Transplant ◽  
Single Agent Chemotherapy

Abstract Background Post-transplant lymphoproliferative disorders (PTLD) develop in the setting of immunosuppression following solid organ transplant or allogeneic stem cell transplant (alloSCT). Other iatrogenic immunodeficiency-associated lymphoproliferative disorders (‘PTLD-like’) can occur with the use of immunosuppressive agents for autoimmune or related disorders. The optimal first-line treatment and risk stratification tool for PTLD remains unclear and rituximab (R) monotherapy is often used following a reduction of immunosuppression (RIS), reserving combination chemotherapy for those failing this initial approach. However, this approach may not be suitable in those with high risk disease. The aim of this study was to review the outcome of patients with PTLD and PTLD-like disease, Methods Using the British Columbia Cancer Agency (BCCA) Lymphoid Cancer Database, all patients diagnosed with PTLD and PTLD-like conditions from 1981-2013 were identified, excluding primary CNS lymphoma, low-grade lymphomas and HIV associated lymphomas. Results 104 patients were identified: 86 PTLD and 18 PTLD-like. PTLD: Median age 47 y (range 6-71); 64% male; 60% late onset (> 1 year from transplant); 71% extranodal (EN) disease; 14% graft involved; 49% elevated LDH (n=36, missing n=13); 59% PS > 2 (n=45, missing n=10); 60% prior renal transplant. Pathology: 57% EBV positive (n=43, missing n=11); 2% early lesions, 13% polymorphic, 79% monomorphic (83% DLBCL), 1.1% classical Hodgkin lymphoma (CHL) and 4.7% unknown. All patients underwent initial RIS, followed by: observation (n=23, 27%), single agent rituximab (n=37, 43%), anthracycline based combination chemotherapy + R (n= 9 (n=6 + R), 10%), single agent chemotherapy + R (n=8 (n=4 + R), 9%); 4 (5%) were too frail to treat. With a median follow-up for living patients of 4.0 y (range 0.8-16.2 y), the 3-y OS and 3-y TTP were 50% and 48%, respectively. Polymorphic cases had a more favorable outcome compared to monomorphic cases with a 3-y OS of 91% vs. 45% (p=0.029) and a 3-y TTP of 73% vs. 44% (p=0.037). Monomorphic PTLD prognostic factors (n=63): In univariate analysis for TTP, an elevated LDH (p=0.006), poor PS >2 (p=.0012), EN sites > 1 (p=0.005), B symptoms (p=0.0019) and GI (p=0.022), kidney (p=0.009) and hepatic (p<0.00001) involvement were all associated with an inferior TTP. Similarly, elevated LDH (p= 0.028), poor PS (p=0.0001) and kidney involvement (p=0.027) were associated with a poor OS. A high IPI score was associated with an inferior outcome: 3-y OS and 3-y TTP for low (0,1) (n=20), intermediate (2,3) (n=34) and high risk (4,5) (n=14) groups were 69%, 40%, and 21% (p=0.03) and 83%, 28%, and 14% (p<0.0001), respectively. For monomorphic DLBCL cases receiving single agent rituximab (n=29), a higher IPI was also associated with a worse 3-y OS (76%, 64%, and 20%, p=0.018) and 3-y TTP (67%, 27%, and 20%, p=0.03) for the low, intermediate and high risk groups, respectively. PTLD-like: Median age 63 y (range 26-74); 50% male; 51% EN disease; 33% LDH elevated (n=6); 44% PS > 2 (n=7, missing n=2); 92% EBV positive (n= 12, missing n=5). Pathology: 1 polymorphic (6%); 15 monomorphic (83%) (DLBCL n=11, 73%, DLBCL/CHL grey zone lymphoma n=2, 13%), 1 CHL (6%), 1 Hodgkin-like (6%), 1 unknown (6%). The majority of patients had a history of rheumatoid arthritis (n=10, 56%) and had been on treatment with methotrexate (n=10, 56%). The median time from onset of autoimmune disorder to the development of PTLD-like disease was 11 y (0.16-50) and the median duration of drug exposure prior to the development of the PTLD-like disease was 5 y (0.16-15y). All patients underwent RIS, followed by observation (n=6, 32%); single agent rituximab (n=4, 21%); anthracycline based combination chemotherapy + R (n=6, 37%; R, n=4); or single agent chemotherapy + R (n=1, 5.3%); 1 was too frail. With a median follow-up of 4.9 y (range 0.3-17 y), the 3-y TTP and OS were 65% and 77%, respectively. Conclusion For PTLD, a select group of patients with a low IPI score appear to have high cure rates with single agent rituximab. For those with multiple IPI factors a risk-adapted strategy with earlier use of chemotherapy may be preferred. In the group with PTLD-like disease we observed Hodgkin lymphoma and Hodgkin-like proliferations but also grey zone lymphomas, the latter of which has not been previously reported. Patients with PTLD-like disorders have a more favorable outcome than those with PTLD. Disclosures: Klasa: Roche Canada: Research Funding. Sehn:Roche/ Genentech: Consultancy, Honoraria, Research Funding. Villa:Celgene: Honoraria; Lundbeck: Honoraria; Roche: Honoraria, Research Funding. Shenkier:Roche Canada: Research Funding. Connors:Roche Canada: Research Funding; F Hoffmann-La Roche: Research Funding. Savage:F Hoffmann-La Roche: Research Funding; Roche Canada: Research Funding.

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