scholarly journals Phase II Study of the Efficacy and Safety of Pembrolizumab for Relapsed/Refractory Classic Hodgkin Lymphoma

2017 ◽  
Vol 35 (19) ◽  
pp. 2125-2132 ◽  
Author(s):  
Robert Chen ◽  
Pier Luigi Zinzani ◽  
Michelle A. Fanale ◽  
Philippe Armand ◽  
Nathalie A. Johnson ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Phase Ii ◽  
Safety Profile ◽  
Response Rate ◽  
Phase Ii Study ◽  
Complete Response ◽  
Salvage Chemotherapy ◽  
Brentuximab Vedotin ◽  
Classic Hodgkin Lymphoma ◽  
Programmed Death

Purpose Hodgkin Reed-Sternberg cells harbor alterations in chromosome 9p24.1, leading to overexpression of programmed death-ligand 1 (PD-L1) and PD-L2. Pembrolizumab, a programmed death 1–blocking antibody, demonstrated a high overall response rate (ORR) in patients with relapsed or refractory classic Hodgkin lymphoma (rrHL) in phase I testing. Methods KEYNOTE-087 ( ClinicalTrials.gov identifier, NCT02453594) was a single-arm phase II study of pembrolizumab in three cohorts of patients with rrHL, defined on the basis of lymphoma progression after (1) autologous stem cell transplantation (ASCT) and subsequent brentuximab vedotin (BV); (2) salvage chemotherapy and BV, and thus, ineligible for ASCT because of chemoresistant disease; and (3) ASCT, but without BV after transplantation. Patients received pembrolizumab 200 mg once every 3 weeks. Response was assessed every 12 weeks. The primary end points were ORR by central review and safety. Results A total of 210 patients were enrolled and treated (69 in cohort 1, 81 in cohort 2, and 60 in cohort 3). At the time of analysis, patients received a median of 13 treatment cycles. Per central review, the ORR was 69.0% (95% CI, 62.3% to 75.2%), and the complete response rate was 22.4% (95% CI, 16.9% to 28.6%). By cohort, ORRs were 73.9% for cohort 1, 64.2% for cohort 2, and 70.0% for cohort 3. Thirty-one patients had a response ≥ 6 months. The safety profile was largely consistent with previous pembrolizumab studies. Conclusion Pembrolizumab was associated with high response rates and an acceptable safety profile in patients with rrHL, offering a new treatment paradigm for this disease.

Brentuximab Vedotin Followed By ABVD in Patients with Previously Untreated Hodgkin Lymphoma. a Pilot Phase II Study

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3088-3088 ◽  
Author(s):  
Pier Luigi Zinzani ◽  
Stefano Luminari ◽  
Francesco Merli ◽  
Emanuela Anna Pesce ◽  
Stephane Chauvie ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Phase Ii ◽  
Overall Response Rate ◽  
Response Rate ◽  
Phase Ii Study ◽  
Complete Response ◽  
Pilot Phase ◽  
First Line ◽  
Overall Response

Abstract active and well tolerated single agent in the treatment of heavily pretreated Hodgkin lymphoma patients. In this pilot phase II study patients with previously untreated HL underwent sequential regimen consisting in 2 cycles of BV before doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) +/- radiotherapy (RT). The primary endpoint of the study was the response to BV assessed by positron emission tomography (PET) after the 2 cycles (PET2), defined as reduction of Deauville score or, in case of no change in Deauville score, as any reduction in standard uptake value (SUV) intensity compared to basal SUV. Between April and October 2013, 12 patients with a median age at diagnosis of 36 years (range, 19-70), 11 stage I-IIA and 1 stage IIIA, were enrolled. BV was administered as scheduled and at the full dose of 1.8 mg/kg in all patients. After the 2 cycles of BV, the overall response rate was 91%, comprising of ten (83%) complete responses and one (8%) partial metabolic response. The non responding patient had stage III and showed a new lesion at PET2. After ABVD +/- RT, the overall response rate was 100% with 11 complete responses and 1 partial response (converting from progression disease). At a median follow up of 8 months, all 11 patients are still in complete response, while the remaining one relapsed. During BV therapy, the only grade 3 adverse events were transient and asymptomatic increase in liver transaminases (n=3, 25%) and gamma glutamyl transpeptidase (n=2, 17%). During ABVD +/- RT grade III-IV neutropenia occurred in 9 (75%) patients. All toxicities were transient and resolved with growth factor support. Two cycles of BV as first line-treatment in limited stage HL induced an outstanding complete response rate with limited toxicity and reducing the need of chemotherapy. Waiting for a longer follow up to assess the duration of response, our data (sequential administration of immunotherapy and chemotherapy) should be considered the starting point for further studies in first line therapy for limited stage HL patients. Disclosures No relevant conflicts of interest to declare.

Targeted Beacopp Variants In Patients With Newly Diagnosed Advanced Stage Classical Hodgkin Lymphoma: Interim Results Of a Randomized Phase II Study

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4344-4344 ◽  
Author(s):  
Peter Borchmann ◽  
Dennis A. Eichenauer ◽  
Annette Plütschow ◽  
Stefanie Kreissl ◽  
Michael Fuchs ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Complete Response ◽  
Brentuximab Vedotin ◽  
Advanced Stage ◽  
Entire Treatment Period ◽  
Randomized Phase Ii ◽  
Grade 3 ◽  
Targeted Beacopp

Abstract Rationale BEACOPPescalated (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) has substantially improved the outcome for patients with advanced stage Hodgkin Lymphoma (HL) achieving an overall survival of 95% at five years. Although this certainly is the most important endpoint for these mainly young patients, there still is concern about the toxicities of this intensified chemotherapy regimen. Brentuximab vedotin (BV) is an anti-CD30 directed antibody-drug conjugate that has shown very promising single-agent activity and good tolerability in HL. We aimed at improving the toxicity profile of BEACOPPescalated while maintaining its efficacy by introducing BV (targeted BEACOPP). Methods Two modified BEACOPP regimens were developed. In a more conservative variant (BrECAPP: BV, etoposide, cyclophosphamide, doxorubicin, procarbazine, prednisone), we replaced vincristine by BV and omitted bleomycin. In the more experimental variant (BrECADD: BV, etoposide, cyclophosphamide, doxorubicin, dacarbazine, dexamethasone) we additionally replaced procarbazine by dacarbazine to reduce gonadal toxicity, reduced the dose of etoposide to decrease risk of second acute myeloid leukemia while slightly increasing the dose of doxorubicin to maintain efficacy, and introduced dexamethasone (day 1-4) substituting for prednisone (day 1-14) to avoid immunosuppressive steroid treatment during neutropenia (please see table 1). Both regimens are administered q21d for 6 cycles. This is an ongoing randomized phase II study with the combined primary endpoint being the PET-based complete response rate after chemotherapy and the complete remission rate at final restaging including early follow-up. Here we report on the first 48 patients (planned n=100). Results The study started in October 2012. 48 patients have been enrolled by June 2013 and are included in this analysis. Median age is 29 years (range 19-60 years), 60% are male, and 83% have Ann-Arbor stage III or IV disease. 14 patients have been staged after 6 cycles of chemotherapy, 6 in the BrECAPP and 8 in the BrECADD arm. Four of these patients have not reached a complete response. The 95% confidence interval for the number of treatment successes is 42% to 92% and contains both the margin for failure (65%) as well as the margin for success (85%). Regarding feasibility, 6 of 15 patients (60%) with 6 cycles of chemotherapy required no dose reductions of etoposide, cyclophosphamide or doxorubicin during the entire treatment period (corresponding number for 6 cycles of BEACOPPescalated in the HD15 study: 50%). Hematological toxicity grade 3 or 4 of the targeted BEACOPP variants was documented in 26 of 32 patients (81%) with at least 1 cycle of chemotherapy documented (corresponding number for 4-6 cycles of BEACOPPescalated in the GHSG HD15 study: 91.7%), and grade 3 or 4 organ toxicity in 1 patient (3%, GHSG HD15 study: 14.1%). Four patients reported symptoms of peripheral sensory neuropathy so far (grade 1 n=2; grade 2 n=2). BV was not given in the 6th cycle in two of these patients. Conclusion These ongoing phase II trial results indicate that anti-CD30 targeted BEACOPP variants may be well feasible without compromising the efficacy associated with BEACOPPescalated. Enrollment is ongoing and updated results will be presented. Disclosures: Borchmann: Takeda: Honoraria, Research Funding. Off Label Use: Brentuximab vedotin first line Treatment of Hodgkin´s Lymphoma. Diehl:Takeda: Membership on an entity’s Board of Directors or advisory committees. Engert:Takeda: Consultancy.

The VcR-CVAD Regimen Produces a High Complete Response Rate in Untreated Mantle Cell Lymphoma (MCL): First Analysis of E1405 – A Phase II Study of VcR-CVAD with Maintenance Rituximab for MCL.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1661-1661 ◽  
Author(s):  
Brad S Kahl ◽  
Hailun Li ◽  
Mitchell R Smith ◽  
Randy D. Gascoyne ◽  
Elisabeth Paietta ◽  
...  
Keyword(s):  
Phase Ii ◽  
Research Funding ◽  
Response Rate ◽  
Complete Response Rate ◽  
Phase Ii Study ◽  
Cell Lymphoma ◽  
Complete Response ◽  
Mantle Cell ◽  
Grade 3

Abstract Abstract 1661 Poster Board I-687 Introduction One approach to improving outcomes in Mantle Cell Lymphoma (MCL) is to incorporate newer targeted agents into standard chemotherapy regimens. As the proteasome inhibitor bortezomib (Velcade‘) achieved a 33% response rate in relapsed MCL, we hypothesized that the incorporation of Velcade (Vc) into a modified R-hyperCVAD chemotherapy backbone would result in a high complete response rate (CR). The new regimen, VcR-CVAD, was tested for safety and efficacy in a phase II study within the Wisconsin Oncology Network (UW) and demonstrated a CR rate of 77% (Kahl, ASH 2008). To determine the safety and efficacy of this regimen in a cooperative group setting, we initiated E1405: a phase II study of VcR-CVAD with maintenance rituximab (MR) for untreated MCL. Methods Eligible patients had histologically confirmed, previously untreated MCL, PS 0-2, and adequate end organ function. The treatment plan included: Velcade 1.3 mg/m2 days 1 and 4, rituximab 375 mg/m2 IV day 1, cyclophosphamide 300 mg/m2 IV over 3 hrs q 12 hrs X 6 doses days 1-3, doxorubicin 50 mg/m2 continuous infusion over 48 hrs days 1-2, vincristine 1 mg IV day 3, dexamethasone 40 mg po days 1-4. Cycles were repeated every 21 days for 6 cycles and all patients received G-CSF support. Patients achieving SD, PR, or CR received MR administered as 4 weekly treatments every 6 months for 2 years (protocol therapy). Patients had an option to receive high dose chemotherapy and autologous stem cell transplantation (off protocol) rather than MR. The primary endpoint of the trial was the CR rate, incorporating PET imaging, to VcR-CVAD induction therapy. Results Seventy-six eligible patients were enrolled between 5/07 and 10/08. Baseline characteristics include median age 62 (40-76), 59M:17F, 91% stage III/IV, and 39% with elevated LDH. Sixty-four patients (84%) completed VcR-CVAD induction therapy. Reasons for treatment discontinuation included PD (1), toxicity (4), patient preference (2), and other/unknown (5). Response information is available on 74 patients while data is outstanding on 2 patients. The ORR was 96% (73/76; 95% CI, 89%-99%), CR rate 75% (57/76; 95% CI, 64%-84%) and the PR rate 21% (16/76; 95% CI, 13%-32%). Six of the PR patients were coded as such because of protocol violations in which a post-treatment bone marrow biopsy or PET scan was not obtained. The CR rate in the 68 completely restaged patients was 84%. Forty-four patients proceeded to planned MR while 21 patients went off protocol to SCT consolidation. Median follow up is currently too short (9 months) to assess PFS and OS. The major toxicity of the treatment regimen was expected myelosuppression. Grade 3-4 non hematologic toxicities were rare. No patients developed grade 3-4 neuropathy. There were no treatment related deaths. Conclusion The VcR-CVAD induction produced high overall response (96%) and CR rate (75%) in a representative MCL patient population treated on a cooperative group protocol. The CR rate was high and comparable to the UW pilot study (77%). No episodes of severe painful peripheral neuropathy were reported using the reduced vincristine dosage and the overall toxicity profile was very acceptable. Longer follow up is needed to determine if the high CR rate will translate into improved PFS and OS. Disclosures Kahl: Genentech: Consultancy, Research Funding; Millennium: Consultancy, Research Funding. Off Label Use: Bortezomib as front line treatment in MCL. Smith:Genentech: Research Funding; Millennium: Research Funding. Advani:Seattle Genetics, Inc.: Research Funding. Horning:Genentech: Honoraria, Research Funding.

Results from a pivotal phase II study of brentuximab vedotin (SGN-35) in patients with relapsed or refractory Hodgkin lymphoma (HL).

2011 ◽  
Vol 29 (15_suppl) ◽  
pp. 8031-8031 ◽  
Author(s):  
R. W. Chen ◽  
A. K. Gopal ◽  
S. E. Smith ◽  
S. M. Ansell ◽  
J. D. Rosenblatt ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Brentuximab Vedotin ◽  
Pivotal Phase ◽  
Refractory Hodgkin Lymphoma

scholarly journals Brentuximab vedotin followed by ABVD +/− radiotherapy in patients with previously untreated Hodgkin lymphoma: final results of a pilot phase II study

Haematologica ◽  
2015 ◽  
Vol 101 (4) ◽  
pp. e139-e141 ◽  
Author(s):  
Massimo Federico ◽  
Stefano Luminari ◽  
Cinzia Pellegrini ◽  
Francesco Merli ◽  
Emanuela Anna Pesce ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Brentuximab Vedotin ◽  
Pilot Phase

Salvage therapies in transplant-eligible relapsed classic Hodgkin lymphoma, are novel regimens better?

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 7530-7530
Author(s):  
Sanjal Desai ◽  
Yucai Wang ◽  
Allison Claire Rosenthal ◽  
Craig B. Reeder ◽  
David James Inwards ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Progression Free Survival ◽  
Complete Response ◽  
Autologous Stem Cell Transplant ◽  
Brentuximab Vedotin ◽  
Cell Transplant ◽  
Multivariate Models ◽  
Bulky Disease ◽  
Classic Hodgkin Lymphoma ◽  
Significant Difference

7530 Background: Clinical trials of novel salvage therapies (ST) have encouraging outcomes for relapsed/refractory classic Hodgkin lymphoma (R/R cHL) eligible for autologous stem cell transplant (ASCT). In this observational study, we report efficacies and outcomes of different ST in ASCT-eligible R/R cHL. Methods: Consecutive ASCT-eligible R/R cHL pts at 3 Mayo Clinic sites were included. Demographics and clinical variables at relapse were recorded by medical records review. Time to event endpoints were defined from relapse. Univariate associations were confirmed in multivariate models of age, sex, B symptoms, stage, bulky disease (BD, single mass > 6 cm) extra nodal disease (END), primary refractory disease (PRD) and early relapse (ER, within 1 year). Results: From Jan 2008 to May 2020, 207 ASCT-eligible pts with R/R cHL were included. Median age was 33 (24-43) years, 53% were male, 52% had advanced stage, 24% had BD, 36% had B symptoms, 41% had END, 11% had PRD and 43% had ER. All patients received ST and underwent ASCT; 43 (21%) received 2 ST, 14 (7%) 3 ST and 4 (0.5%) received 4 ST. 6 groups of ST were identified: ifosfamide, carboplatin and etoposide (ICE), bendamustine/brentuximab (BBV), brentuximab vedotin (BV), gemcitabine-based therapy (Gem), checkpoint inhibitor (CPI), and others. Table lists response to first line ST. BBV had significantly higher overall response rate (ORR) and complete response (CR) as first ST in univariate and multivariate models. 114 (79%) after ICE, 30 (97%) after BBV, 15 (56%) after BV, 25 (76%) after Gem, 8 (73%) after CPI and 15 (79%) after other ST underwent ASCT. Higher number of pts were bridged to ASCT after BBV than ICE (p<0.01). 110 (53%) went to ASCT in CR, 74 (36%) in partial response (PR) and 11% in progressive disease (PD). 43 received BV maintenance (BVm) after ASCT. Pts going to ASCT in PR or PD had significantly lower progression free survival (PFS) compared to pts in CR (2 yr PFS: 62%, 18% vs 77%, respectively, p<0.0001) in univariate and multivariate models. There was no difference in PFS and overall survival (OS) by type of ST. BVm was associated with higher PFS (HR 0.3 (CI95 0.2-0.8)) and higher number of ST was associated with lower OS (HR 2 (CI95 1.4-3)) in multivariate model (p<0.001). For pts transplanted in CR, there was no significant difference in PFS and OS by type of ST but higher number of ST predicted lower OS (HR 2.4 (CI95 1.2-3.5), p<0.01). Conclusions: Type of ST did not predict survival, response to and number of ST did. For pts with CR, number of ST not type of ST predicted survival. BBV had higher response rates, higher rates of bridge to ASCT, and may be a preferable ST than ICE. Large, randomized trials are needed to evaluate efficacy of BBV compared to ICE.[Table: see text]

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