scholarly journals Controversies in the management of early-stage Hodgkin lymphoma

Hematology ◽  
2021 ◽  
Vol 2021 (1) ◽  
pp. 234-239
Author(s):  
Kristie A. Blum
Keyword(s):  
Hodgkin Lymphoma ◽  
Checkpoint Inhibitors ◽  
Early Stage ◽  
Progression Free Survival ◽  
Risk Groups ◽  
Similar Efficacy ◽  
Interim Pet ◽  
Positron Emission ◽  
Frontline Treatment ◽  
Frontline Therapy

Abstract Positron emission tomography (PET)–adapted chemotherapy and radiotherapy approaches are currently used for the initial treatment of early-stage Hodgkin lymphoma (HL) with progression-free survival and overall survival exceeding 85% and 95%, respectively. However, despite general agreement on the prognostic value of interim PET in HL, frontline treatment approaches vary among institutions with respect to how pretreatment clinical risk factors determine treatment selection, the definition of PET negativity, which chemotherapy regimen to initiate and how many cycles to administer, and when to incorporate radiation. Furthermore, as recent trials have confirmed improved efficacy and manageable toxicity when brentuximab and checkpoint inhibitors are combined with frontline regimens such as doxorubicin, vinblastine, and dacarbazine in advanced-stage HL, these agents are now under evaluation as frontline therapy in early-stage HL. A number of issues will affect the use of these agents in early-stage HL, including the costs, early and late toxicities with these agents, patient population (favorable or unfavorable risk groups), how to incorporate them (concurrently or sequentially), and whether they can ultimately replace cytotoxic therapy with similar efficacy and fewer late effects. Future treatment paradigms for early-stage HL may change significantly once randomized studies are completed incorporating these agents into frontline therapy. Ideally, frontline use of brentuximab and checkpoint inhibitors in early-stage HL will result in improved outcomes compared with current PET-adapted approaches with decreased risks of late toxicities that continue to afflict long-term survivors of HL.

scholarly journals Serum levels of TARC, MDC, IL-10, and soluble CD163 in Hodgkin lymphoma: a SWOG S0816 correlative study

Blood ◽  
2019 ◽  
Vol 133 (16) ◽  
pp. 1762-1765 ◽  
Author(s):  
Eric D. Hsi ◽  
Hongli Li ◽  
Andrew B. Nixon ◽  
Heiko Schöder ◽  
Nancy L. Bartlett ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Prognostic Score ◽  
Progression Free Survival ◽  
Serum Levels ◽  
Interleukin 10 ◽  
Serum Samples ◽  
Barr Virus ◽  
Soluble Cd163 ◽  
Interim Pet ◽  
Positron Emission

Abstract Serum soluble chemokines/cytokines produced by Hodgkin cells and the tumor microenvironment might be of value as biomarkers in classic Hodgkin lymphoma (cHL). We assessed serum thymus and activation-related chemokine (TARC), macrophage-derived chemokine (MDC), interleukin-10 (IL-10), and soluble CD163 (sCD163) levels at baseline, time of interim fluorodeoxyglucose positron emission tomography (PET), and after therapy in cHL patients treated on S0816, an intergroup phase 2 response-adapted study evaluating escalated therapy for interim PET (PET2)–positive patients (www.clinicaltrials.gov #NCT00822120). Epstein-Barr virus (EBV) status was assessed, and 559 serum samples were evaluated for TARC, MDC, IL-10, and sCD163 by immunoassay. EBV positivity correlated with higher sCD163 and IL-10 levels but lower TARC levels. While baseline biomarker levels were not associated with outcome, sCD163 levels at the time of PET2 were associated with favorable progression-free survival (PFS), adjusting for PET2 status. After therapy TARC, MDC, and IL-10 correlated with PFS and overall survival (OS) on univariable analysis, which remained significant adjusting for international prognostic score. When also adjusting for end-of-therapy PET results, TARC and IL-10 remained significantly associated with shorter PFS and OS. Exploratory analysis in PET2-negative patients showed that elevated posttherapy TARC and IL-10 levels were associated with PFS. Serum cytokine levels correlate with outcome in cHL and should be investigated further in risk-adapted cHL trials.

scholarly journals Doxorubicin, vinblastine, and gemcitabine (CALGB 50203) for stage I/II nonbulky Hodgkin lymphoma: pretreatment prognostic factors and interim PET

Blood ◽  
2011 ◽  
Vol 117 (20) ◽  
pp. 5314-5320 ◽  
Author(s):  
David J. Straus ◽  
Jeffrey L. Johnson ◽  
Ann S. LaCasce ◽  
Nancy L. Bartlett ◽  
Lale Kostakoglu ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Hodgkin Lymphoma ◽  
Progression Free Survival ◽  
Prognostic Features ◽  
Interim Pet ◽  
Phase 2 Trial ◽  
Positron Emission ◽  
Before And After ◽  
Group B

AbstractTo reduce doxorubicin, bleomycin, vinblastine and dacarbazine toxicity, the Cancer and Leukemia Group B conducted a phase 2 trial of doxorubicin, vinblastine, and gemcitabine for newly diagnosed, nonbulky stages I and II Hodgkin lymphoma. Ninety-nine assessable patients received 6 cycles of doxorubicin 25 mg/m2, vinblastine 6 mg/m2, and gemcitabine 800 mg/m2 (1000 mg/m2 in first 6) on days 1 and 15 every 28 days. Computed tomography (CT) and positron emission tomography (PET) were performed before and after 2 and 6 cycles. Complete remission (CR)/CR unconfirmed was achieved in 72 of 99 patients (72.7%) and partial remission in 24 of 99 patients (24.2%). The CR rate was 81% when using PET criteria. Two patients have died of Hodgkin lymphoma progression. Median follow-up for nonprogressing patients is 3.3 years. The progression-free survival (PFS) at 3 years was 77% (95% confidence interval, 68%-84%). The relapse rate was less than 10% for patients with favorable prognostic factors. The 2-year PFS for cycle 2 PET-negative and -positive patients was 88% and 54%, respectively (P = .0009), compared with 89% and 27% for cycle 6 PET-negative and -positive patients (P = .0001). Although the CR rate and PFS were lower than anticipated, patients with favorable prognostic features had a low rate of relapse. Cycle 2 PET and cycle 6 PET were predictive of PFS. This clinical trial is registered at www.clinicaltrials.gov as #NCT00086801.

Positron Emission Tomography–Driven Strategy in Advanced Hodgkin Lymphoma: Prolonged Follow-Up of the AHL2011 Phase III Lymphoma Study Association Study

2022 ◽  
Author(s):  
René-Olivier Casasnovas ◽  
Reda Bouabdallah ◽  
Pauline Brice ◽  
Julien Lazarovici ◽  
Hervé Ghesquieres ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Hodgkin Lymphoma ◽  
Emission Tomography ◽  
Phase Iii ◽  
Second Primary ◽  
Second Primary Malignancy ◽  
Interim Pet ◽  
Positron Emission ◽  
Study Results

PURPOSE The AHL2011 study (ClinicalTrials.gov identifier: NCT01358747 ) demonstrated that a positron emission tomography (PET)-driven de-escalation strategy after two cycles of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP) provides similar progression-free survival (PFS) and overall survival (OS) and reduces early toxicity compared with a nonmonitored standard treatment. Here, we report, with a prolonged follow-up, the final study results. METHODS Patients with advanced Hodgkin lymphoma (stage III, IV, or IIB with mediastinum/thorax ratio > 0.33 or extranodal involvement) age 16-60 years were prospectively randomly assigned between 6 × BEACOPP and a PET-driven arm after 2 × BEACOPP delivering 4 × ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) in PET2– and 4 × BEACOPP in PET2+ patients. PET performed after four cycles of chemotherapy had to be negative to complete the planned treatment. RESULTS In total, 823 patients were enrolled including 413 in the standard arm and 410 in the PET-driven arm. With a 67.2-month median follow-up, 5-year PFS (87.5% v 86.7%; hazard ratio [HR] = 1.07; 95% CI, 0.74 to 1.57; P = .67) and OS (97.7% in both arms; HR = 1.012; 95% CI, 0.50 to 2.10; P = .53) were similar in both randomization arms. In the whole cohort, full interim PET assessment predicted patients' 5-year PFS (92.3% in PET2–/PET4–, 75.4% [HR = 3.26; 95% CI, 18.3 to 5.77] in PET2+/PET4– and 46.5% [HR = 12.4; 95% CI, 7.31 to 19.51] in PET4+ patients, respectively; P < .0001) independent of international prognosis score. Five-year OS was also affected by interim PET results, and PET2+/PET4– patients (93.5%; HR = 3.3; 95% CI, 1.07 to 10.1; P = .036) and PET4+ patients (91.9%; HR = 3.756; 95% CI, 1.07 to 13.18; P = .038) had a significant lower OS than PET2–/PET4– patients (98.2%). Twenty-two patients (2.7%) developed a second primary malignancy, 13 (3.2%) and 9 (2.2%) in the standard and experimental arms, respectively. CONCLUSION The extended follow-up confirms the continued efficacy and favorable safety of AHL2011 PET-driven strategy, which is noninferior to standard six cycles of BEACOPP. PET4 provides additional prognostic information to PET2 and allows identifying patients with particularly poor prognosis.

Total tumor burden in lymphoma – an evolving strong prognostic parameter

2021 ◽  
pp. 20210448
Author(s):  
Michel Meignan ◽  
Anne-Segolene Cottereau ◽  
Lena Specht ◽  
N. George Mikhaeel
Keyword(s):  
Tumor Volume ◽  
Cell Lymphoma ◽  
Strong Predictor ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Risk Groups ◽  
Metabolic Tumor Volume ◽  
Tumor Burden ◽  
Interim Pet ◽  
Fdg Pet Ct

Total metabolic tumor volume (TMTV), a new parameter extracted from baseline FDG-PET/CT, has been recently proposed by several groups as a prognosticator in lymphomas before first-line treatment. TMTV, the sum of the metabolic volume of each lesion, is an index of the metabolically most active part of the tumor and highly correlates with the total tumor burden. TMTV measurement is obtained from PET images processed with different software and techniques, many being now freely available. In the various lymphoma subtypes where it has been measured, such as diffuse large B-cell lymphoma, Hodgkin lymphoma, Follicular Lymphoma, and Peripheral T-cell lymphoma, TMTV has been reported as a strong predictor of outcome (progression-free survival and overall survival) often outperforming the clinical scores, molecular predictors, and results of interim PET. Combined with these scores, TMTV improves the stratification of the populations into risk groups with different outcomes. TMTV cut-off separating the high-risk from the low-risk population impacts the outcome whatever the technique used for its measurement and an international harmonization is ongoing. TMTV is a unique and easy tool that could replace the surrogate of tumor burden included in the prognostic indexes used in lymphoma and help tailor therapy. Other parameters extracted from the baseline PET may give an information on the dissemination of this total tumor volume such as the maximum distance between the lesions. Trials based on TMTV would probably demonstrate its predictive value.

scholarly journals Balancing risk and benefit in early-stage classical Hodgkin lymphoma

Blood ◽  
2018 ◽  
Vol 131 (15) ◽  
pp. 1666-1678 ◽  
Author(s):  
Paul J. Bröckelmann ◽  
Stephanie Sasse ◽  
Andreas Engert
Keyword(s):  
Disease Control ◽  
Hodgkin Lymphoma ◽  
Early Stage ◽  
Therapeutic Option ◽  
Classical Hodgkin Lymphoma ◽  
Excellent Outcome ◽  
Limited Stage ◽  
Interim Pet ◽  
Increased Risk

Abstract With defined chemotherapy and radiotherapy (RT) and risk-adapted treatment, early-stage classical Hodgkin lymphoma (HL) has become curable in a majority of patients. Hence, a major current goal is to reduce treatment-related toxicity while maintaining long-term disease control. Patients with early-stage favorable disease (ie, limited stage without risk factors [RFs]) are frequently treated with 2 cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (2×ABVD) followed by 20-Gy involved-field or involved-site RT (IF/ISRT). In patients with early-stage unfavorable disease (ie, limited stage with RFs), 4 cycles of chemotherapy are usually consolidated with 30-Gy IF/ISRT. Compared with 4×ABVD, 2 cycles of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (2×BEACOPPescalated) followed by 2×ABVD improved 5-year progression-free survival (PFS), with similar 5-year overall survival. Recently, treatment strategies based on [18F]fluorodeoxyglucose positron emission tomography (PET) response were evaluated. In early-stage unfavorable HL, a majority of patients achieved a negative interim PET after 2×ABVD and an excellent outcome after 4×ABVD, whereas in those with a positive interim PET, 2×BEACOPPescalated improved 5-year PFS. Furthermore, a PET-guided RT approach was evaluated to decrease long-term toxicity. Although both the RAPID and H10 trials reported poorer disease control without RT, PET-guided omission of RT can constitute a valid therapeutic option in patients with an increased risk of RT-associated toxicity (eg, because of sex, age, or disease localization). Implementation of drugs such as the anti-CD30 antibody-drug conjugate brentuximab vedotin or the anti–programmed death 1 antibodies nivolumab or pembrolizumab might allow further reduction of overall mortality and improve quality of life in affected patients.

scholarly journals Allo-HSCT in transplant-naïve patients with Hodgkin lymphoma: a single-arm, multicenter study

2019 ◽  
Vol 3 (24) ◽  
pp. 4264-4270 ◽  
Author(s):  
Emma Das-Gupta ◽  
Kirsty J. Thomson ◽  
Adrian J. C. Bloor ◽  
Andrew D. Clark ◽  
Stephen Mackinnon ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Chronic Gvhd ◽  
Progression Free Survival ◽  
Complete Response ◽  
Primary Objective ◽  
Mixed Chimerism ◽  
Hematopoietic Stem ◽  
Positron Emission ◽  
Computed Tomography Scanning ◽  
Unrelated Donors

Abstract We evaluated the role of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in transplant-naïve patients with relapsed/refractory Hodgkin lymphoma (HL) who failed to attain metabolic complete response (mCR) to 1 to 2 lines of salvage chemotherapyThose with residual but nonprogressive disease assessed by positron emission tomography/computed tomography scanning were eligible. An additional 1 to 2 cycles of salvage therapy were permissible in those with progressive disease or when required to bridge to allo-HSCT, with additional imaging at baseline before transplantation. Conditioning consisted of carmustine, etoposide, cytarabine, melphalan, and alemtuzumab. Donor lymphocyte infusions (DLI) were administered for mixed chimerism or residual or relapsed disease. Eleven patients had sibling donors, 13 had HLA-matched unrelated donors, and 7 had HLA-mismatched unrelated donors. There were no graft failures, and no episodes of grade 4 acute graft-versus-host disease (GVHD); only 19.4% of patients had grade 2 to 3 GVHD, and 22.2% had extensive chronic GVHD. The non-relapse mortality rate was 16.1% (95% confidence interval [CI], 7.1%-34.5%). Relapse incidence was 18.7% (95% CI, 8.2%-39.2%). The study met its primary objective, with a 3-year progression-free survival of 67.7% (95% CI, 48.4%-81.2%). Survival outcomes were equivalent in those with residual metabolically active disease immediately before transplantation (n = 24 [70.8%; 95% CI, 17.2%-83.7%]). Two of the 5 patients who relapsed received DLI and remained in mCR at latest follow-up, with a 3-year overall survival of 80.7% (95% CI, 61.9%-90.8%). We demonstrate encouraging results that establish a potential role for allo-HSCT in selected high-risk patients with HL. This trial was registered at www.clinicaltrials.gov as #NCT00908180.

Mediastinal Gray Zone Lymphoma with Features Intermediate between Classical Hodgkin Lymphoma and Primary Mediastinal B-Cell Lymphoma

2016 ◽  
Vol 136 (3) ◽  
pp. 186-190 ◽  
Author(s):  
Haa-Na Song ◽  
Seok Jin Kim ◽  
Young Hyeh Ko ◽  
Won Seog Kim
Keyword(s):  
B Cell ◽  
Hodgkin Lymphoma ◽  
Systemic Chemotherapy ◽  
Cell Lymphoma ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Gray Zone ◽  
Bulky Disease ◽  
Gray Zone Lymphoma ◽  
Frontline Therapy

Background: Mediastinal gray zone lymphoma (MGZL) shares clinical characteristics with primary mediastinal B-cell lymphoma (PMBCL) and nodular sclerosing Hodgkin lymphoma (NSHL). However, MGZL is extremely rare, and an appropriate treatment for it has not yet been established. Methods: We retrospectively analyzed 8 patients who were treated with systemic chemotherapy for MGZL between 2007 and 2014. Results: The patients with MGZL were predominantly young and male (median age 26 years), and 62.5% of patients had bulky disease. The overall response rate (ORR) and complete remission (CR) rate were both 75% (6/8) for all treated patients The median overall survival (OS) and progression-free survival (PFS) was 40.7 and 3.9 months, respectively. Most responders (4/6, 66.7%) were treated with R-CHOP (rituximab + cyclophosphamide, hydroxydaunorubicin, Oncovin and prednisolone) as the frontline therapy. The CR rate of patients who received R-CHOP and those who did not was 100% (4/4) and 50% (2/4), respectively. Particularly striking was the finding that the median PFS of patients who received R-CHOP frontline chemotherapy was 11.4 months, which was superior to the median PFS of patients who did not receive R-CHOP. Conclusions: Of the 8 patients with MGZL who were treated with systemic chemotherapy, superior treatment responses were observed in patients who received R-CHOP as the frontline therapy.

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