scholarly journals RELAPSES IN INTERIM PET NEGATIVE LIMITED STAGE HODGKIN LYMPHOMA PATIENTS RECEIVING ABVD WITH OR WITHOUT RADIOTHERAPY–ANALYSIS OF EORTC/FIL/LYSA H10 AND UK NCRI RAPID TRIALS

2021 ◽  
Vol 39 (S2) ◽  
Author(s):  
I. Aurer ◽  
A. Neven ◽  
V. Fiaccadori ◽  
N. Counsell ◽  
E. Phillips ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Limited Stage ◽  
Interim Pet

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.

Early Interim FDG-PET Scan Predicts Outcome in Non-Bulky Limited Stage Hodgkin Lymphoma, but may Not Guide Use of Consolidative Radiotherapy.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1453-1453 ◽  
Author(s):  
Jeffrey A. Barnes ◽  
Ann S. LaCasce ◽  
Christiana E. Toomey ◽  
Ephraim Hochberg ◽  
Alfred I. Lee ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Complete Response ◽  
Primary Treatment ◽  
Pet Scan ◽  
Rank Test ◽  
Limited Stage ◽  
Interim Pet ◽  
Consolidative Radiotherapy ◽  
Pet Scans

Abstract The standard treatment for limited-stage Hodgkin lymphoma has been combined modality therapy, but late toxicities of radiation have prompted investigation of chemotherapy alone in low risk patients. Initial trials have demonstrated a small increased risk of relapse if radiation is omitted, but no difference in overall survival. We investigated the predictive value of interim FDG-PET (PET) scans in nonbulky limited stage patients, and asked whether PET may guide the use of consolidative radiotherapy for patients in complete remission after chemotherapy alone. A total of 68 patients with nonbulky limited stage disease were identified at our institutions with interim PET performed after 2–3 cycles of chemotherapy. All patients received anthracycline-based chemotherapy with curative intent. PET scan interpretations were extracted by chart review of radiology reports. The median age was 35 (range 18–77). Fifty-nine patients had disease in the neck and mediastinum, 6 had inguinal disease, and 2 in Waldeyer’s ring. Fifty-two patients were stage IIA, 4 were IIB, 10 were IA, and 1 was IB. Radiation was included at the discretion of the treating physician. Complete response required a negative PET scan. The complete response (CR) rate was 88%. Fifty-one patients (75%) had a negative interim PET, and 17 (25%) had a positive interim PET. Interim PET− patients were more likely to achieve a CR at the end of therapy compared to interim PET+ patients (98% vs. 59%; p=0.0001, Fisher’s exact test). At a median follow up of 32 months (range 3–70), the progression-free (PFS) and overall survival (OS) for the entire series were 85% and 100%, respectively. Interim PET− patients had an improved PFS compared to PET+ patients (90% vs. 71%; p=0.032, log rank test). Among the 60 patients who achieved a CR, 50 (83%) were interim PET−, and 10 (17%) were interim PET+. There was no difference in PFS between interim PET+ and PET− patients who achieved a CR. The most important predictor of PFS was achievement of CR at the end of therapy (92% vs. 37%; p<0.0001, log rank test). Consolidative radiotherapy was employed in 18 (30%) CR patients. No difference in PFS was observed based on inclusion of radiation. Among 10 CR patients with a positive interim PET scan, 3 received radiation and 7 did not. All 7 interim PET+ patients treated with chemotherapy alone remained disease free. Eight patients had primary treatment failure (4 partial responses and 4 with progressive disease). Seven of 8 treatment failures were interim PET+. There were 6 relapses in this series occurring at a median of 18 months (range 13–24), 5 occurring in an initially involved field. Five had achieved a CR to initial therapy; 1 had received consolidative radiotherapy. Five of 6 patients had a negative interim PET scan. All patients with treatment failure or relapse were alive at last follow up following salvage therapy. In our series, a positive interim PET scan after 2–3 cycles is predictive of an inferior PFS in patients with nonbulky limited stage Hodgkin lymphoma, but this difference is largely driven by an increase in primary treatment failures among interim PET+ patients. Patients with a positive interim PET who achieve a CR at the completion of chemotherapy have favorable outcomes similar to patients with negative interim PET scans, regardless of inclusion of consolidative radiation. These data suggest that positive interim PET scans denote biologically more aggressive disease but may not be useful in guiding the use of consolidative radiotherapy for patients in complete remission. These observations warrant validation in prospective clinical trials.

scholarly journals Interim PET-directed therapy in limited-stage Hodgkin lymphoma initially treated with ABVD

Haematologica ◽  
2018 ◽  
Vol 103 (12) ◽  
pp. e590-e593 ◽  
Author(s):  
Diego Villa ◽  
Laurie H. Sehn ◽  
Christina Aquino-Parsons ◽  
Petter Tonseth ◽  
David W. Scott ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Limited Stage ◽  
Interim Pet

scholarly journals A Phase II Study of Brentuximab Vedotin Plus Adriamycin and Dacarbazine without Radiation in Non-Bulky Limited Stage Classical Hodgkin Lymphoma

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 1654-1654 ◽  
Author(s):  
Jeremy S. Abramson ◽  
Robert A. Redd ◽  
Jeffrey A. Barnes ◽  
Elizabeth Bengtson ◽  
Ronald W. Takvorian ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Sensory Neuropathy ◽  
Brentuximab Vedotin ◽  
Classical Hodgkin Lymphoma ◽  
Limited Stage ◽  
Interim Pet ◽  
End Of Treatment ◽  
Grade 3 ◽  
Peripheral Sensory

Abstract BACKGROUND: ABVD with or without radiation is standard therapy for limited stage HL, but carries risks of bleomycin-lung injury and radiation toxicity. Brentuximab vedotin (BV) is an anti-CD30 antibody drug conjugate which is highly active in relapsed classical HL. We previously combined BV with AVD in limited stage non-bulky classical HL which resulted in a high CR rate, but at the cost of increased neutropenia, neutropenic fever, and neuropathy, likely related to the overlapping toxicity profile with vinblastine. Similar toxicity findings were also observed with BV-AVD in advanced stage classical Hodgkin lymphoma. We therefore evaluated BV plus AD (BV-AD) without radiation therapy for non-bulky stage I-II classical HL with the goal of reducing toxicity and maintaining high rates of inducing CR. METHODS: This is a multicenter single arm open label phase 2 study. Patients received BV 1.2 mg/kg plus standard dose adriamycin and dacarbazine on days 1 and 15 of each 28 day cycle. GCSF prophylaxis was not included. Patients received 4 or 6 cycles of BV-AD based on the results of an interim PETCT scan performed following cycle 2. PET negativity was defined as Deauville scores 1-3. Patients in CR on interim PETCT received 4 total cycles of therapy; patients in PR completed 6 cycles. The primary endpoint is complete response rate (CRR) at end of treatment. A sample size of 34 was required to detect an end of treatment CRR of 95% with 91% power and alpha error of 0.09. RESULTS: 34 patients were enrolled. Median age is 36 (range 18-63). Stage is IA (3), IB (1), IIA (29) and IIB (1). Risk is classified per the GHSG criteria as early unfavorable in 47%, and favorable in 53%. The interim CR rate is 94%. Accordingly, 32 interim PET negative patients (94%) received 4 total cycles of therapy, and 2 interim PET positive patients (6%) received 6 total cycles of therapy. No patients received consolidative radiation therapy, per protocol. The primary endpoint of end of treatment CR rate is 100%. At a median follow-up of 15 months, the FFS, PFS and OS are all 100%. The most common adverse events of any grade are nausea (79%), peripheral sensory neuropathy (56%), fatigue (50%), constipation (38%), alopecia (35%) and neutropenia (24%). Most toxicities were low grade, with only 15% of subjects experiencing any grade 3 toxicity, and there were no grade 4 or 5 toxicities. Specifically, 2 patients had grade 3 neutropenia, and 1 patient each had grade 3 nausea/vomiting, pneumonia and thromboembolic event. Peripheral sensory neuropathy was grade 1 in 17 patients, and grade 2 in 2 patients. There were no cases of neutropenic fever. CONCLUSIONS: BV-AD for 4-6 cycles induces high interim and end of treatment CR rates of 94% and 100%, respectively, allowing 4 total cycles of therapy in most patients. The PFS, FFS and OS are all 100% at last follow up. Toxicity appears mild and notable for a low incidence of neutropenia, alopecia, and moderate peripheral neuropathy. This promising regimen avoids bleomycin, vinblastine, radiation and primary GCSF prophylaxis with resultant low toxicity and preserved high efficacy rates in patients with early favorable and early unfavorable non-bulky limited stage classical Hodgkin lymphoma. Follow up for this trial is ongoing. Figure. Figure. Disclosures Abramson: Merck: Consultancy; Seattle Genetics: Consultancy; Karyopharm: Consultancy; Verastem: Consultancy; Amgen: Consultancy; Humanigen: Consultancy; Juno Therapeutics: Consultancy; Gilead: Consultancy; Novartis: Consultancy; Bayer: Consultancy; Celgene: Consultancy. Sokol:Mallinckrodt Pharmaceuticals: Consultancy; Seattle Genetics: Consultancy; Spectrum Pharmaceuticals: Consultancy. Jacobsen:Merck: Consultancy; Seattle Genetics: Consultancy. LaCasce:Seattle Genetics: Consultancy, Honoraria; Research to Practice: Speakers Bureau; Humanigen: Consultancy, Honoraria; Bristol-Myers Squibb: Other: Data safety and monitoring board.

scholarly journals A Phase 2 Trial of Induction Chemotherapy with ABVD Followed By Brentuximab Vedotin Consolidation in Patients with Previously Untreated Non-Bulky Stage I or II Hodgkin Lymphoma

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4431-4431 ◽  
Author(s):  
Steven I. Park ◽  
Kristy L. Richards ◽  
Oludamilola Olajide ◽  
Nishitha M Reddy ◽  
Nilanjan Ghosh ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Hodgkin Lymphoma ◽  
Induction Chemotherapy ◽  
Brentuximab Vedotin ◽  
Pet Scan ◽  
Limited Stage ◽  
Interim Pet ◽  
Field Radiation ◽  
Involved Field

Abstract Background: Treatment of Hodgkin lymphoma (HL) requires a careful balance between providing enough therapy to cure the disease and avoiding unnecessary treatment that could result in excessive long-term treatment-related complications. The preferred treatment option for limited stage non-bulky HL currently involves the use of combined chemotherapy and involved-field radiation therapy. Given the unclear overall survival advantage and the long-term side effects associated with consolidative radiation, the use of this modality remains one of the most controversial topics in the treatment of HL. Therefore, alternative consolidation approaches are worthy of exploration for treatment of limited stage non-bulky HL. Brentuximab vedotin has been associated with favorable response rates in patients with relapsed or refractory HL. We hypothesize that brentuximab vedotin may be safe and effective in eradicating residual disease after induction chemotherapy and may potentially replace radiation therapy for consolidation in patients with newly diagnosed limited stage non-bulky HL. Methods: In this phase 2 multicenter study, patients with non-bulky (< 7.5 cm) stage I or II HL are being enrolled to determine the efficacy and safety of brentuximab vedotin when administered for consolidation after a standard chemotherapy with ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) (ClinicalTrials.gov #NCT01578967). The primary objective of the study is to estimate the proportion of patients who achieve PET-negative disease (Deauville score of 2 or less) after induction chemotherapy followed by consolidation with brentuximab vedotin. Involved-field radiation is recommended only if the PET scan is positive at the completion of therapy with brentuximab vedotin. Patients received 2 to 6 cycles of ABVD based on their baseline risk factors and the interim PET scan result; patients with favorable disease with negative interim PET received 2 cycles, favorable disease with positive interim PET or unfavorable disease with negative interim PET received 4 cycles, and unfavorable disease with positive interim PET received 6 cycles of ABVD. Approximately 6 to 8 weeks after the induction chemotherapy, 1.8 mg/kg of brentuximab vedotin was given every 3 weeks for 6 cycles for consolidation. Results: Interim analysis was performed per protocol for futility and safety after 15 evaluable patients were enrolled since April 2012. Out of 15 evaluable patients, 8 patients have completed 6 cycles of brentuximab vedotin, and the remaining 7 patients are currently under active treatment. The median age was 28 years (range 19 – 58), and 7 patients (47%) presented with unfavorable disease defined by the presence of B symptoms, ESR > 50, or > 3 sites of disease. All patients had masses measuring less than 7.5 cm in diameter except one patient who requested an exception to the eligibility criteria for a conglomerate mediastinal mass measuring 10 cm. No grade 3 or above adverse events have been observed with brentuximab vedotin therapy. No grade 2 or above peripheral neuropathy or pulmonary toxicity has been reported. Ten out of 12 patients, who completed ABVD, achieved PET-negative disease after 2 cycles of ABVD, and all 7 patients who completed brentuximab vedotin achieved PET-negative disease and remain in remission with a median follow-up of 7.6 months (range 5.6 – 15). Thus far, none of the treated patients on this protocol required consolidative radiation therapy. Conclusion: In this interim analysis of 15 patients with newly diagnosed limited stage non-bulky HL, brentuximab vedotin as consolidation therapy demonstrates promising safety and clinical activity following ABVD. Enrollment is currently open with the target accrual of 40 patients to assess the feasibility of achieving PET-negative disease and thereby avoiding radiation therapy in at least 85% of patients who receive ABVD followed by brentuximab vedotin consolidation. Table: PET results in HL patients who received ABVD followed by BV Consolidation Interim-PET2 (n = 12) Post ABVD (n = 12) Post BV (n = 7) Deauville 1 0 1 4 Deauville 2 10 11 3 Deauville 3 2 0 0 Deauville ≥ 4 0 0 0 PET, positron emission tomography; HL, Hodgkin lymphoma; ABVD, doxorubicin, bleomycin, vinblastine, dacarbazine; BV, brentuximab vedotin; Interim-PET-2, PET scan after 2 cycles of ABVD; Post ABVD, PET scan after 2 to 6 cycles of ABVD; Post BV, PET scan after 6 cycles of brentuximab vedotin Disclosures Park: Seattle Genetics: Research Funding; Teva: Research Funding; Janssen: Travel, Travel Other. Off Label Use: Brentuximab vedotin in previously untreated Hodgkin lymphoma patients.

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.

scholarly journals Point/counterpoint: early-stage Hodgkin lymphoma and the role of radiation therapy

Hematology ◽  
2012 ◽  
Vol 2012 (1) ◽  
pp. 313-321 ◽  
Author(s):  
Ralph M. Meyer ◽  
Richard T. Hoppe
Keyword(s):  
Clinical Trials ◽  
Radiation Therapy ◽  
Hodgkin Lymphoma ◽  
Early Stage ◽  
Trial Protocol ◽  
Radiation Oncologist ◽  
Limited Stage ◽  
Considerable Debate

Abstract The results of recent clinical trials for the management of limited-stage Hodgkin lymphoma have led to considerable debate, especially regarding the role of radiation therapy. This review highlights those recent trials and provides perspectives regarding their interpretation from a radiation oncologist and a hematologist. The trial protocol is available at http://www.nejm.org/doi/suppl/10.1056/NEJMoa1111961/suppl_file/nejmoa1111961_protocol.pdf.

Limited Utility of PET-CT and CT Imaging Beyond Treatment Completion in Limited Stage Hodgkin Lymphoma Patients

2019 ◽  
Vol 105 (1) ◽  
pp. E476
Author(s):  
G. Glober ◽  
J.R. Gunther ◽  
S.A. Milgrom ◽  
B.R. Korivi ◽  
C.T. Jensen ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Treatment Completion ◽  
Ct Imaging ◽  
Limited Stage ◽  
Pet Ct
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